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Wu X, Lu X, Zhang W, Zhong X, Bu H, Zhang Z. Development and validation of a 10-gene signature for predicting recurrence risk in HR+/HER2- early breast cancer undergoing chemo-endocrine therapy. Breast 2025; 82:104484. [PMID: 40288025 PMCID: PMC12056407 DOI: 10.1016/j.breast.2025.104484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 03/06/2025] [Accepted: 04/23/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND While existing multi-gene assays aid adjuvant treatment decisions, no gene signature has identified HR+/HER2- early breast cancer (EBC) patients at high recurrence risk post-chemo-endocrine therapy (C-ET). METHODS Clinical data and RNA sequencing information from 1457 HR+/HER2- breast cancer patients were collected from West China Hospital, the GEO database, and the TCGA database. Using univariate Cox regression, gene set enrichment analysis, and LASSO regression, ten key genes associated with recurrence were identified. A comprehensive prognostic model was developed by combining the 10-gene risk score with clinicopathological features, and a nomogram was created to predict 3-, 5-, and 7-year recurrence-free survival (RFS). The model's performance was evaluated using AUC and decision curve analysis (DCA). RESULTS The 10-gene risk score was significantly associated with recurrence risk of HR+/HER2- EBC after C-ET and effectively distinguished between high-risk and low-risk patients (training: HR: 6.37, P < 0.001; validation: HR: 4.51, P < 0.001). It maintained consistent stratification efficacy across different treatment regimens, clinical stages, and grades. Compared to existing multi-gene signatures (21-gene, 70-gene, EndoPredict, PAM50, GGI), HR+/HER2- EBC patients identified as high-risk by the 10-gene risk score exhibited a higher 10-year cumulative recurrence rate following C-ET. In multivariate Cox regression analysis, the 10-gene risk score remained an independent prognostic factor in both the training and validation sets. The comprehensive model, integrating the 10-gene score and clinicopathological features, showed high predictive accuracy (AUC: 0.734, 0.778, 0.792 for 3, 5, 7 years in training; 0.691, 0.715, 0.709 in validation). CONCLUSION The 10-gene risk score can serve as a tool to predict recurrence risk in HR+/HER2- EBC patients following C-ET, assisting clinicians in developing personalized treatment plans for high-risk patients and ultimately improving patient prognosis.
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Affiliation(s)
- Xiaoyan Wu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, China
| | - Xunxi Lu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, China
| | - Wenchuan Zhang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaorong Zhong
- Institute for Breast Health Medicine, Cancer Center, Breast Center, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Bu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, China
| | - Zhang Zhang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Breast Pathology and Artificial Intelligence, West China Hospital, Sichuan University, Chengdu, China.
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Park JM, Lee SJ, Ahn JH, Yoon CS, Park S. Characteristics of premenopausal breast cancer patients with a midrange 21-gene recurrence score. Ann Surg Treat Res 2025; 108:219-230. [PMID: 40226167 PMCID: PMC11982449 DOI: 10.4174/astr.2025.108.4.219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 12/25/2024] [Accepted: 01/13/2025] [Indexed: 04/15/2025] Open
Abstract
Purpose The results of the TAILORx trial have shown that premenopausal patients with intermediate Oncotype Dx (ODx) recurrence score of 16-25 may benefit from adjuvant chemotherapy. In addition, the clinicopathological features showed the information complementary to ODx results. However, the characteristics may vary depending on menopausal status even in the same score. This study aimed to analyze the differences in the clinical characteristics by menopausal status. Methods This study conducted a retrospective analysis of 756 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and node-negative breast cancer who underwent the ODx test from July 2013 to December 2020 at the Severance Hospital. Results Of the 756 patients, 261 patients were postmenopausal, and 495 were premenopausal. The premenopausal patients with a midrange ODx had similar clinicopathological features as compared to those with a high ODx. Conversely, the postmenopausal patients with a midrange ODx did not show significantly different clinicopathological features from those with a low ODx, whereas a difference was seen as compared to those with a high ODx. Conclusion In this study, unlike the postmenopausal patients, some of the clinicopathological characteristics of the premenopausal patients with a midrange ODx were closer to those with a high ODx than those with a low ODx. In the premenopausal patients with a midrange ODx, considering the baseline characteristic itself, there was a significant difference between those with a low ODx when compared with postmenopausal patients. Therefore, more aggressive treatment decisions may be helpful in premenopausal patients with a midrange ODx.
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Affiliation(s)
- Jung Min Park
- Department of Surgery, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
- Yonsei University Graduate School of Medicine, Seoul, Korea
| | - Suk Jun Lee
- Division of Breast Surgery, Department of Surgery, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Jee Hyun Ahn
- Division of Breast Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Chan Seok Yoon
- Department of Surgery, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
| | - Seho Park
- Division of Breast Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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Nguyen Van Long F, Poirier B, Desbiens C, Perron M, Paquet C, Ouellet C, Diorio C, Lemieux J, Nabi H. First versus second-generation molecular profiling tests: How both can guide decision-making in early-stage hormone-receptor positive breast cancers? Cancer Treat Rev 2025; 135:102909. [PMID: 40054315 DOI: 10.1016/j.ctrv.2025.102909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 04/08/2025]
Abstract
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) tumors represent the most common types of early-stage breast cancer. However, their response to adjuvant systemic treatments varies widely due to tumor heterogeneity. Current decisions for adjuvant treatment rely heavily on clinical and pathological characteristics, which can sometimes lead to overtreatment. Accurately identifying patients who will benefit from adjuvant chemotherapy at an individual level remains a challenge. Multigene profiling assays are now widely used in clinics to better assess recurrence risk and chemotherapy response for HR+ disease. In this report, we examine the advantages and limitations of two widely used molecular profiling tests-Oncotype DX and Prosigna. Both Oncotype DX and Prosigna have been demonstrated to be effective prognostic tools in early breast cancer, with Oncotype DX also being validated as a predictive tool to guide chemotherapy decisions. We focus on studies that directly compare these molecular tests and discuss how their strengths can be leveraged to improve clinical decision-making for early-stage HR+ breast cancers. Finally, we highlight remaining knowledge gaps and propose directions for future research.
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Affiliation(s)
- Flora Nguyen Van Long
- Oncology Axis, Centre Hospitalier Universitaire de Québec Research Center - Université Laval (CRCHUQc-UL), Quebec city, QC G1V 4G2, Canada
| | - Brigitte Poirier
- Oncology Axis, Centre Hospitalier Universitaire de Québec Research Center - Université Laval (CRCHUQc-UL), Quebec city, QC G1V 4G2, Canada; Centre des maladies du sein, CHU de Québec-Université Laval, Quebec city, QC G1V 4G2, Canada
| | - Christine Desbiens
- Oncology Axis, Centre Hospitalier Universitaire de Québec Research Center - Université Laval (CRCHUQc-UL), Quebec city, QC G1V 4G2, Canada; Centre des maladies du sein, CHU de Québec-Université Laval, Quebec city, QC G1V 4G2, Canada
| | - Marjorie Perron
- Pathology department, CHU de Québec-Université Laval, Quebec city, QC G1V 4G2, Canada
| | - Claudie Paquet
- Pathology department, CHU de Québec-Université Laval, Quebec city, QC G1V 4G2, Canada
| | - Cathie Ouellet
- Pathology department, CHU de Québec-Université Laval, Quebec city, QC G1V 4G2, Canada
| | - Caroline Diorio
- Oncology Axis, Centre Hospitalier Universitaire de Québec Research Center - Université Laval (CRCHUQc-UL), Quebec city, QC G1V 4G2, Canada; Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada
| | - Julie Lemieux
- Oncology Axis, Centre Hospitalier Universitaire de Québec Research Center - Université Laval (CRCHUQc-UL), Quebec city, QC G1V 4G2, Canada; Centre des maladies du sein, CHU de Québec-Université Laval, Quebec city, QC G1V 4G2, Canada
| | - Hermann Nabi
- Oncology Axis, Centre Hospitalier Universitaire de Québec Research Center - Université Laval (CRCHUQc-UL), Quebec city, QC G1V 4G2, Canada; Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada.
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Keogan A, Nguyen TNQ, Bouzy P, Stone N, Jirstrom K, Rahman A, Gallagher WM, Meade AD. Prediction of post-treatment recurrence in early-stage breast cancer using deep-learning with mid-infrared chemical histopathological imaging. NPJ Precis Oncol 2025; 9:18. [PMID: 39825009 PMCID: PMC11748621 DOI: 10.1038/s41698-024-00772-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Accepted: 11/25/2024] [Indexed: 01/20/2025] Open
Abstract
Predicting long-term recurrence of disease in breast cancer (BC) patients remains a significant challenge for patients with early stage disease who are at low to intermediate risk of relapse as determined using current clinical tools. Prognostic assays which utilize bulk transcriptomics ignore the spatial context of the cellular material and are, therefore, of limited value in the development of mechanistic models. In this study, Fourier-transform infrared (FTIR) chemical images of BC tissue were used to train deep learning models to predict future disease recurrence. A number of deep learning models were employed, with champion models employing two-dimensional and two-dimensional-separable convolutional networks found to have predictive performance of a ROC AUC of approximately 0.64, which compares well to other clinically used prognostic assays in this space. All-digital chemical imaging may therefore provide a label-free platform for histopathological prognosis in breast cancer, opening new horizons for future deployment of these technologies.
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Affiliation(s)
- Abigail Keogan
- Radiation and Environmental Science Centre, Physical to Life Sciences Research Hub, Technological University Dublin, Dublin, Ireland
- School of Physics, Clinical and Optometric Sciences, Technological University Dublin, City Campus, Dublin, Ireland
| | | | - Pascaline Bouzy
- Department of Physics and Astronomy, University of Exeter, Exeter, UK
| | - Nicholas Stone
- Department of Physics and Astronomy, University of Exeter, Exeter, UK
| | - Karin Jirstrom
- Division of Oncology and Therapeutic Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Arman Rahman
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
- UCD School of Medicine, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - William M Gallagher
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Aidan D Meade
- Radiation and Environmental Science Centre, Physical to Life Sciences Research Hub, Technological University Dublin, Dublin, Ireland.
- School of Physics, Clinical and Optometric Sciences, Technological University Dublin, City Campus, Dublin, Ireland.
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Li J, Yao J, Qi L. Identification of TUBB2A as a Cancer-Immunity Cycle-Related Therapeutic Target in Triple-Negative Breast Cancer. Mol Biotechnol 2024; 66:2467-2480. [PMID: 37742297 DOI: 10.1007/s12033-023-00880-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 08/28/2023] [Indexed: 09/26/2023]
Abstract
OBJECTIVE Triple negative breast cancer (TNBC) is a malignant subtype of breast cancer characterized by the absence of ER, PR, and HER2. We aimed to explore target gene from the perspective of cancer-immunity cycle, providing insights into treatment of TNBC. METHODS We obtained TNBC samples from METABRIC database and downloaded 4 datasets from GEO database, as well as an IMvigor210 dataset. WGCNA was applied to screen genes associated with cancer-immunity cycle in TNBC. GO, KEGG and GSEA analyses were performed to explore the target gene's potential functions and pathways. The binding motifs with transcription factors were predicted with FIMO. Immune infiltration analysis was conducted by CIBERSORT. RESULTS TUBB2A was screened out as our target gene which was negatively correlated with T cell recruitment in cancer-immunity cycle. TUBB2A expressed higher in TNBC samples than in normal samples. High expression of TUBB2A was associated with poor prognosis of TNBC. 12 transcription factors and 5 miRNAs might regulate TUBB2A's expression. The infiltration ratios of 7 types of immune cells such as CD8+ T cells, naive CD4+ T cells and activated memory CD4+ T cells were significantly lower in TUBB2A high expression group. TUBB2A was a potential drug target. CONCLUSION We screened a cancer-immunity cycle-related gene TUBB2A which was negatively correlated with T cell recruiting in TNBC. TUBB2A expressed higher in TNBC samples than in normal samples, associated with poor prognosis.
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Affiliation(s)
- Jia Li
- Department of Breast Surgical Oncology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Xinghualing District, Taiyuan, 030013, Shanxi Province, People's Republic of China
| | - Jingchun Yao
- Department of Head and Neck, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Xinghualing District, Taiyuan, 030013, Shanxi Province, People's Republic of China
| | - Liqiang Qi
- Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan, Huawei South Road, Chaoyang District, Beijing, 100021, People's Republic of China.
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Li L, Yu J, Shen K, Chen X. The 21-Gene Recurrence Score Assay Improved Multidisciplinary Treatment Compliance in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: An Analysis of 2,323 Patients. J Breast Cancer 2024; 27:163-175. [PMID: 38769684 PMCID: PMC11221206 DOI: 10.4048/jbc.2023.0248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 02/28/2024] [Accepted: 03/24/2024] [Indexed: 05/22/2024] Open
Abstract
PURPOSE The 21-gene recurrence score (RS) can guide adjuvant chemotherapy decisions in the multidisciplinary treatment (MDT) of patients with early breast cancer. This study aimed to evaluate the influence of the 21-gene RS assay on patient' compliance with MDT and its association with disease outcomes. METHODS Patients diagnosed with pN0-1, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer between January 2013 and June 2019 were enrolled. A logistic regression model was used to identify parameters associated with treatment adherence. Prognostic indicators were evaluated using the Cox proportional hazard models. RESULTS After the assay, patients were less likely to violate the treatment plan (14.9% vs. 23.1%, p < 0.001), and higher compliance rates were observed for chemotherapy (p = 0.042), radiotherapy (p = 0.012), and endocrine therapy (p < 0.001). Multivariable analysis demonstrated that the 21-gene RS assay (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.09-1.88; p = 0.009) was independently associated with MDT compliance. Moreover, compliance with MDT was independently associated with better disease-free survival (hazard ratio, 0.43; 95% CI, 0.29-0.64; p < 0.001), regardless of the 21-gene RS assay (interaction p = 0.842). CONCLUSION The 21-gene RS assay improved the MDT compliance rate in patients with early breast cancer. Adherence to MDT is associated with a better prognosis.
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Affiliation(s)
- Liangqiang Li
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Jing Yu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kunwei Shen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaosong Chen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Wang J, Chen H, Koenig J, Wu Y, Bedrosian I, Arun B, Ding Q, Khazai L, Resetkova E, Huo L, Sneige N, Albarracin C. Discordance of Oncotype DX scores in synchronous bilateral and unilateral multifocal breast cancers. Breast Cancer Res Treat 2024; 203:73-83. [PMID: 37751078 DOI: 10.1007/s10549-023-07119-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 08/25/2023] [Indexed: 09/27/2023]
Abstract
PURPOSE Oncotype DX, a 21-gene expression profiling test, has become standard of care in the management of estrogen receptor (ER)-positive breast cancer. In multifocal tumors, it is unclear whether testing of the different foci is necessary. We evaluated the concordance of Oncotype DX recurrence scores (RS) between 2 tumor foci in synchronous bilateral or unilateral multifocal tumors and characterized pathological predictors of discordance. METHODS We reviewed 713 ER+, HER2- primary invasive breast cancer patients with Oncotype RS and identified 17 bilateral synchronous patients (34 tumors) and 13 unilateral multifocal patients (26 tumors) with available Oncotype RS on all foci. Discordance in Oncotype RS between synchronous tumors was recorded and associations with clinicopathologic features including tumor size, histology, Nottingham histologic grade, progesterone receptor staining, and Ki67 index were analyzed. RESULTS Bilateral synchronous tumors were present in older patients (median age 59 years) and had larger tumor (median size 17 mm) and more discordant histology (10/17, 59%) as compared to unilateral multifocal tumors (median age 49 years, p < 0.01; median tumor size 12 mm, p = 0.01; discordant histology 2/13, 15%, p = 0.03). Oncotype RS were discordant in 47% (8/17) of bilateral and 54% (7/13) of unilateral multifocal tumors. Concordant Oncotype RS was associated with similar histologic grade and Ki67 index in 78% (7/9) of bilateral and 100% (6/6) of multifocal tumors. In contrast, only 25% (2/8) of bilateral (p = 0.06) and 14% (1/7) of unilateral multifocal (p < 0.01) cases with discordant Oncotype RS had concordant histology grades and Ki67 levels. In synchronous tumors with discordant Oncotype RS and Ki67 index, all (4/4) foci with higher RS had higher Ki67 index. CONCLUSION Discordance of Oncotype RS is common in both bilateral and unilateral multifocal breast cancer and is likely associated with discordant histologic grade or Ki67.
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Affiliation(s)
- Jing Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hui Chen
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 085, G1.3617B, Houston, TX, 77030, USA.
| | - Jenna Koenig
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Yun Wu
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Isabelle Bedrosian
- Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Banu Arun
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Qingqing Ding
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Laila Khazai
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Erika Resetkova
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lei Huo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nour Sneige
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Constance Albarracin
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 085, G1.3617A, Houston, TX, 77030, USA.
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Chen S, Thacker C, Wang S, Young KA, Hoffman RL, Blansfield JA. Adherence Disparities and Utilization Trends of Oncotype Dx Assay: A National Cancer Database Study. J Surg Res 2023; 286:65-73. [PMID: 36758322 DOI: 10.1016/j.jss.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 12/11/2022] [Accepted: 01/08/2023] [Indexed: 02/09/2023]
Abstract
INTRODUCTION Oncotype Dx (ODX) is a genetic assay that analyzes tumor recurrence risk and provides chemotherapy recommendations for T1-T2 stage, hormone receptor-positive, human epidermal growth factor receptor-negative, and nodal-negative breast cancer patients. Despite its established validity, the utilization of this assay is suboptimal. The study aims to evaluate factors that are associated with adherence rate with the testing guidelines and examine changes in utilization trends. METHODS This is a retrospective study, utilizing data from the National Cancer Database from 2010 to 2017. Patients who met the ODX testing guidelines were first evaluated for testing adherence. Secondly, all patients who underwent ODX testing were assessed to evaluate the trend in ODX utilization. RESULTS A total of 429,648 patients met the criteria for ODX, and 43.4% of this population underwent testing. Advanced age, racial minorities, low-income status, well-differentiated tumor grade, uninsured status, and treatment at community cancer centers were associated with a decreased likelihood of receiving ODX in eligible patients. Additionally, a notable amount of testing was performed on patients who did not meet the ODX testing criteria. Among the 295,326 patients that underwent ODX testing, 16.6% of patients were node-positive and 1.8% had T3 or T4 stage tumors. CONCLUSIONS A considerable number of patients who were eligible for ODX did not receive it, indicating potential barriers to care and disparities in breast cancer treatment. ODX usage has been expanded to broader patient populations, indicating more research is needed to validate the effectiveness of the assay in these patient groups.
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Affiliation(s)
- Shuyi Chen
- Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania.
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Turner BM, Finkelman BS, Hicks DG, Numbereye N, Moisini I, Dhakal A, Skinner K, Sanders MAG, Wang X, Shayne M, Schiffhauer L, Katerji H, Zhang H. The Rochester Modified Magee Algorithm (RoMMa): An Outcomes Based Strategy for Clinical Risk-Assessment and Risk-Stratification in ER Positive, HER2 Negative Breast Cancer Patients Being Considered for Oncotype DX ® Testing. Cancers (Basel) 2023; 15:cancers15030903. [PMID: 36765860 PMCID: PMC9913115 DOI: 10.3390/cancers15030903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Multigene genomic profiling has become the standard of care in the clinical risk-assessment and risk-stratification of ER+, HER2- breast cancer (BC) patients, with Oncotype DX® (ODX) emerging as the genomic profile test with the most support from the international community. The current state of the health care economy demands that cost-efficiency and access to testing must be considered when evaluating the clinical utility of multigene profile tests such as ODX. Several studies have suggested that certain lower risk patients can be identified more cost-efficiently than simply reflexing all ER+, HER2- BC patients to ODX testing. The Magee equationsTM use standard histopathologic data in a set of multivariable models to estimate the ODX recurrence score. Our group published the first outcome data in 2019 on the Magee equationsTM, using a modification of the Magee equationsTM combined with an algorithmic approach-the Rochester Modified Magee algorithm (RoMMa). There has since been limited published outcome data on the Magee equationsTM. We present additional outcome data, with considerations of the TAILORx risk-stratification recommendations. METHODS 355 patients with an ODX recurrence score, and at least five years of follow-up or a BC recurrence were included in the study. All patients received either Tamoxifen or an aromatase inhibitor. None of the patients received adjuvant systemic chemotherapy. RESULTS There was no significant difference in the risk of recurrence in similar risk categories (very low risk, low risk, and high risk) between the average Modified Magee score and ODX recurrence score with the chi-square test of independence (p > 0.05) or log-rank test (p > 0.05). Using the RoMMa, we estimate that at least 17% of individuals can safely avoid ODX testing. CONCLUSION Our study further reinforces that BC patients can be confidently stratified into lower and higher-risk recurrence groups using the Magee equationsTM. The RoMMa can be helpful in the initial clinical risk-assessment and risk-stratification of BC patients, providing increased opportunities for cost savings in the health care system, and for clinical risk-assessment and risk-stratification in less-developed geographies where multigene testing might not be available.
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Affiliation(s)
- Bradley M. Turner
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
- Correspondence: ; Tel.: +1-(585)-275-2228; Fax: +1-(585)-341-6725
| | - Brian S. Finkelman
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
| | - David G. Hicks
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
| | - Numbere Numbereye
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
| | - Ioana Moisini
- M. Health Fairview Ridges, Burnsville, MN 55337, USA
| | - Ajay Dhakal
- Department of Medical Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Kristin Skinner
- Department of Surgical Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Mary Ann G. Sanders
- Norton Healthcare, University of Louisville Department of Pathology, Louisville, KY 40292, USA
| | - Xi Wang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
| | - Michelle Shayne
- Department of Medical Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Linda Schiffhauer
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
| | - Hani Katerji
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
| | - Huina Zhang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14620, USA
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Hassan S, Younan R, Patocskai E, Provencher L, Poirier B, Sideris L, Dubé P, Mihalcioiu C, Chabot-Blanchet M, Guertin MC, Boileau JF, Robidoux A. Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec. Oncologist 2022; 27:822-831. [PMID: 35830543 PMCID: PMC9526502 DOI: 10.1093/oncolo/oyac123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 05/26/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The 21-gene Breast Recurrence Score (RS) assay, "the assay", has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada. PATIENTS AND METHODS We conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician's recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician's expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results. RESULTS For the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up. CONCLUSION Altogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer.
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Affiliation(s)
- Saima Hassan
- McPeak Sirois Group, Montreal, QC, Canada
- Division of Surgical Oncology, Department of Surgery, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montreal, QC, Canada
- Centre de Recherche de CHUM (CRCHUM), Institut de Cancer de Montréal, Montreal, QC, Canada
| | - Rami Younan
- McPeak Sirois Group, Montreal, QC, Canada
- Division of Surgical Oncology, Department of Surgery, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montreal, QC, Canada
| | - Erica Patocskai
- McPeak Sirois Group, Montreal, QC, Canada
- Division of Surgical Oncology, Department of Surgery, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montreal, QC, Canada
| | - Louise Provencher
- McPeak Sirois Group, Montreal, QC, Canada
- Centre Hospitalier Universitaire de Quebec, Université Laval, Quebec, QC, Canada
| | - Brigitte Poirier
- McPeak Sirois Group, Montreal, QC, Canada
- Centre Hospitalier Universitaire de Quebec, Université Laval, Quebec, QC, Canada
| | - Luca Sideris
- McPeak Sirois Group, Montreal, QC, Canada
- Hôpital Maisonneuve-Rosemont, Université de Montréal, Montreal, QC, Canada
| | - Pierre Dubé
- McPeak Sirois Group, Montreal, QC, Canada
- Hôpital Maisonneuve-Rosemont, Université de Montréal, Montreal, QC, Canada
| | - Catalin Mihalcioiu
- McPeak Sirois Group, Montreal, QC, Canada
- McGill University Health Centre, Montreal, QC, Canada
| | | | | | - Jean-François Boileau
- McPeak Sirois Group, Montreal, QC, Canada
- Jewish General Hospital, Segal Cancer Centre, McGill University, Montreal, QC, Canada
| | - André Robidoux
- McPeak Sirois Group, Montreal, QC, Canada
- Division of Surgical Oncology, Department of Surgery, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montreal, QC, Canada
- Centre de Recherche de CHUM (CRCHUM), Institut de Cancer de Montréal, Montreal, QC, Canada
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11
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Shen K, Yao L, Zhu J, Gu X, Wang J, Qian W, Zheng Z, Fu D, Wu S. Impact of adjuvant chemotherapy on T1N0M0 breast cancer patients: a propensity score matching study based on SEER database and external cohort. BMC Cancer 2022; 22:863. [PMID: 35941565 PMCID: PMC9358893 DOI: 10.1186/s12885-022-09952-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 07/25/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND There is no clear consensus on the benefits of adjuvant chemotherapy for tumor-node-metastasis (TNM) stage T1 (T1N0M0) breast cancer (BC). Our study investigated the effects of adjuvant chemotherapy on T1N0M0 BC patients. METHODS Seventy-five thousand one hundred thirty-nine patients diagnosed with T1N0M0 BC were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of adjuvant chemotherapy on T1a, T1b, and T1cN0M0 BC, including various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further compare the results between adjuvant chemotherapy and no adjuvant chemotherapy. Additionally, 545 T1N0M0 BC patients treated at the Northern Jiangsu People's Hospital were included as an independent external validation cohort. Univariate and multivariate Cox analyses were used to confirm the effects of adjuvant chemotherapy in T1a, T1b, and T1cN0M0 BC. Survival curves for the different tumor grades and molecular subtypes were plotted using the Kaplan-Meier method. RESULTS Adjuvant chemotherapy demonstrated a statistically significant improvement in overall survival (OS) in T1b and T1c BC, but not in T1a BC. Within T1b BC, adjuvant chemotherapy was found to have effects on grade III, and hormone receptor + (HoR +)/human epidermal growth factor receptor 2 + (HER2 +), HoR-/HER2 + , and HoR-/HER2- molecular subtypes, respectively. Adjuvant chemotherapy was beneficial to OS for grade II/III and T1c BC. Identical results were obtained after PSM. We also obtained similar results with external validation cohort, except that adjuvant chemotherapy made a difference in grade II and T1b BC of the external validation dataset. CONCLUSIONS Partial T1N0M0 BC patients with grade III T1bN0M0, patients with tumor grade II and III T1cN0M0, and excluding those with HoR + /HER2- subtype tumors, could obtain OS benefits from adjuvant chemotherapy.
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Affiliation(s)
- Kaiwen Shen
- Department of General Surgery, Traditional Chinese Medicine Hospital of Kunshan, Suzhou, 215000, Jiangsu, China
| | - Longdi Yao
- Department of General Surgery, Changxing Hospital of Traditional Chinese Medicine, Huzhou, 313100, Zhejiang, China
| | - Jingyuan Zhu
- Department of General Surgery, Traditional Chinese Medicine Hospital of Kunshan, Suzhou, 215000, Jiangsu, China
| | - Ximing Gu
- Department of General Surgery, Traditional Chinese Medicine Hospital of Kunshan, Suzhou, 215000, Jiangsu, China
| | - Jie Wang
- Department of General Surgery, Traditional Chinese Medicine Hospital of Kunshan, Suzhou, 215000, Jiangsu, China
| | - Wei Qian
- Nanjing Medical University, Nanjing, 211166, Jiangsu, China
| | - Zhijian Zheng
- Department of General Surgery, The First People's Hospital of Wenling, Wenling, 317500, Zhejiang, China
| | - Deyuan Fu
- Department of Thyroid and Breast Surgery, Northern Jiangsu People's Hospital, Yangzhou University Medical Academy, Guangling District, Nantong Xi Road, Yangzhou, 225001, Jiangsu, China.
| | - Song Wu
- Department of Thyroid and Breast Surgery, The First People's Hospital of Wenling, Chuanan Nan Road, Chengxi Street, Wenling, 317500, Zhejiang, China.
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12
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Utility of genomic platforms in treatment decisions in axilla-positive breast cancer. Clin Breast Cancer 2022; 22:634-641. [DOI: 10.1016/j.clbc.2022.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 07/12/2022] [Accepted: 07/24/2022] [Indexed: 11/19/2022]
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13
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Tailoring the Omission of Radiotherapy for Early-Stage Breast Cancer Based on Tumor Biology. Semin Radiat Oncol 2022; 32:198-206. [DOI: 10.1016/j.semradonc.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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14
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Triulzi T, Bianchini G, Di Cosimo S, Pienkowski T, Im Y, Bianchi GV, Galbardi B, Dugo M, De Cecco L, Tseng L, Liu M, Bermejo B, Semiglazov V, Viale G, de la Haba‐Rodriguez J, Oh D, Poirier B, Valagussa P, Gianni L, Tagliabue E. The TRAR gene classifier to predict response to neoadjuvant therapy in HER2-positive and ER-positive breast cancer patients: an explorative analysis from the NeoSphere trial. Mol Oncol 2022; 16:2355-2366. [PMID: 34816585 PMCID: PMC9208076 DOI: 10.1002/1878-0261.13141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 10/13/2021] [Accepted: 11/22/2021] [Indexed: 11/07/2022] Open
Abstract
As most erb-b2 receptor tyrosine kinase 2 (HER2)-positive breast cancer (BC) patients currently receive dual HER2-targeting added to neoadjuvant chemotherapy, improved methods for identifying individual response, and assisting postsurgical salvage therapy, are needed. Herein, we evaluated the 41-gene classifier trastuzumab advantage risk model (TRAR) as a predictive marker for patients enrolled in the NeoSphere trial. TRAR scores were computed from RNA of 350 pre- and 166 post-treatment tumor specimens. Overall, TRAR score was significantly associated with pathological complete response (pCR) rate independently of other predictive clinico-pathological variables. Separate analyses according to estrogen receptor (ER) status showed a significant association between TRAR score and pCR in ER-positive specimens but not in ER-negative counterparts. Among ER-positive BC patients not achieving a pCR, those with TRAR-low scores in surgical specimens showed a trend for lower distant event-free survival. In conclusion, in HER2-positive/ER-positive BC, TRAR is an independent predictor of pCR and represents a promising tool to select patients responsive to anti-HER2-based neoadjuvant therapy and to assist treatment escalation and de-escalation strategies in this setting.
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Affiliation(s)
- Tiziana Triulzi
- Department of ResearchFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
| | | | | | - Tadeusz Pienkowski
- Oncology and Breast Diseases DepartmentPostgraduate Medical Education CenterWarsawPoland
| | - Young‐Hyuck Im
- Department of MedicineSamsung Medical CenterSeoulRepublic of Korea
| | | | - Barbara Galbardi
- Department of Medical OncologyIRCCS Ospedale San RaffaeleMilanItaly
| | - Matteo Dugo
- Department of Medical OncologyIRCCS Ospedale San RaffaeleMilanItaly
| | - Loris De Cecco
- DRASTFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
| | - Ling‐Ming Tseng
- Taipei‐Veterans General HospitalNational Yang‐Ming UniversityTaiwan
| | - Mei‐Ching Liu
- Koo Foundation Sun Yat‐Sen Cancer CenterTaipeiTaiwan
| | - Begoña Bermejo
- Hospital Clínico UniversitarioINCLIVA Biomedical Research InstituteValenciaSpain
| | | | - Giulia Viale
- Department of Medical OncologyIRCCS Ospedale San RaffaeleMilanItaly
| | | | - Do‐Youn Oh
- Division of Medical OncologySeoul National University Hospital Cancer Research InstituteSeoul National University College of MedicineRepublic of Korea
| | - Brigitte Poirier
- Centre des Maladies du seinHôpital du Saint‐SacrementCHU de QuébecCanada
| | | | - Luca Gianni
- Fondazione MichelangeloMilanItaly
- Fondazione Gianni BonadonnaMilanItaly
| | - Elda Tagliabue
- Department of ResearchFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
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15
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Yordanova M, Hassan S. The Role of the 21-Gene Recurrence Score ® Assay in Hormone Receptor-Positive, Node-Positive Breast Cancer: The Canadian Experience. Curr Oncol 2022; 29:2008-2020. [PMID: 35323363 PMCID: PMC8947241 DOI: 10.3390/curroncol29030163] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/02/2022] [Accepted: 03/04/2022] [Indexed: 01/02/2023] Open
Abstract
The management of patients with hormone receptor-positive breast cancer has changed dramatically with use of the 21-gene Recurrence Score® (RS) Assay. While the utility of the assay was initially demonstrated among node-negative patients, recent studies have also demonstrated the assay's prognostic and predictive value in node-positive patients. In Canada, the RS assay is reimbursed by provincial health insurance plans, but not all provinces have approved the use of the assay for patients with node-positive disease. Here, we provide an overview of the clinical factors that influence physician recommendation of the RS assay and, alternatively, the impact of the RS assay on patient treatment decisions in Canada. We performed a comprehensive review of the impact of the assay upon physician treatment decisions and cost in node-positive breast cancer patients within Canada and other countries. Furthermore, we evaluated biomarkers that can predict the RS result, in addition to other genomic assays that predict recurrence risk among node-positive patients. Overall, the 21-gene RS assay was shown to be a cost-effective tool that significantly reduced the use of chemotherapy in node-positive breast cancer patients in Canada.
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Affiliation(s)
- Mariya Yordanova
- Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada;
| | - Saima Hassan
- Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3T5, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), l’Institut de Cancer de Montréal, Montréal, QC H2X 0A9, Canada
- Division of Surgical Oncology, Department of Surgery, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC H2X 0C1, Canada
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16
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Zhang S, Fitzsimmons KC, Hurvitz SA. Oncotype DX Recurrence Score in premenopausal women. Ther Adv Med Oncol 2022; 14:17588359221081077. [PMID: 35295864 PMCID: PMC8918761 DOI: 10.1177/17588359221081077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/31/2022] [Indexed: 12/19/2022] Open
Abstract
In the past 20 years, clinicians have shifted away from relying solely on clinicopathologic indicators toward increasing use of multigene expression assays in guiding treatment decisions regarding adjuvant chemotherapy for early-stage hormone receptor (HR)-positive, HER2-negative breast cancer. Oncotype DX Recurrence Score (RS) is one of the most widely used multigene assays when considering indications for adjuvant chemotherapy, and guidelines have recently incorporated its use in women with early HR-positive HER2-negative breast cancer and up to three positive lymph nodes. While multiple retrospective and prospective clinical studies have demonstrated that most women with a low- to mid-range RS (0-25) can safely forgo chemotherapy, premenopausal women remain an important subgroup for which recommendations based on RS are ill-defined. The majority of patients included in clinical trials and retrospective analyses validating the use of RS have been postmenopausal women. In the subgroup of premenopausal women with HR-positive HER2-negative breast cancer, studies indicate that traditional clinicopathologic methods for assessing risk continue to be powerful tools when combined with RS to predict benefit from chemotherapy. This suggests that there is an element of uncaptured risk inherent to the premenopausal state that evades characterization by RS alone. This review describes the evidence that has supported the recommendation of RS in clinical guidelines, specifically focusing on data for its current use in premenopausal women. We review available data regarding the impact of the menstrual cycle on hormonally regulated gene expression, which may drive variations in the RS. Further research on the reliability and interpretation of the RS in the premenopausal subgroup is necessary and represents a gap in knowledge of how the RS should be applied in premenopausal women.
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Affiliation(s)
- Shiliang Zhang
- Department of Internal Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Kasey C. Fitzsimmons
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Sara A. Hurvitz
- Division of Hematology and Oncology, Department of Internal Medicine, University of California Los Angeles, Los Angeles, CA, USA 90095
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17
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Chen K, Wu J, Fang Z, Shao X, Wang X. The Clinical Research and Latest Application of Genomic Assays in Early-Stage Breast Cancer. Technol Cancer Res Treat 2022; 21:15330338221117402. [PMID: 36976899 PMCID: PMC9486269 DOI: 10.1177/15330338221117402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Breast cancer is a kind of malignant tumor that seriously endangers women's life
and health. Once diagnosed, most patients will receive a combination of
treatments to achieve a cure. However, breast cancer is a heterogeneous disease.
Even with the same clinical stage and pathological features, its response to
treatment and postoperative recurrence risk may still be completely different.
With the advent of genomic assay, some patients with early-stage breast cancer
who originally needed treatment can still achieve long-term disease-free
survival without adjuvant chemotherapy, so as to achieve personalized and
accurate treatment mode to a certain extent. In this paper, we reviewed the 5
most widely used and studied genomic panel technologies in breast cancer, namely
Oncotype DX, MammaPrint,
RecurIndex, PAM50, and
EndoPredict, according to accessibility and availability.
Based on the results of the completed or ongoing clinical studies, we summarized
the origin, applicable population, and clinical efficacy of each detection
method, and discussed the potential development prospect of detection technology
in the future.
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Affiliation(s)
- Keyu Chen
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Jiayi Wu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Ziru Fang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Xiying Shao
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Xiaojia Wang
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
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18
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Liu B, Su Q, Xiao B, Zheng G, Zhang L, Yin J, Wang L, Che F, Heng X. RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway. Front Oncol 2021; 11:657029. [PMID: 34912698 PMCID: PMC8666624 DOI: 10.3389/fonc.2021.657029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 11/08/2021] [Indexed: 01/22/2023] Open
Abstract
Angiogenesis plays an important role in tumor initiation and progression of glioma. Seeking for biomarkers associated with angiogenesis is important in enhancing our understanding of glioma biologically and identifying its new drug targets. RNA-sequencing (RNA-seq) data and matched clinical data were downloaded from the CGGA database. A series of filtering analyses were performed to screen for reliable genes: survival, multivariate Cox, ROC curve filtration, and clinical correlation analyses. After immunohistochemical verification, RAB42 was identified as a reliable gene for further single gene analysis. Afterwards, we performed gene set enrichment analysis (GSEA) and co-expression analysis to establish the related molecular mechanisms and signal pathways in glioma. Finally, the gene functions and the mechanisms were investigated in vitro experiments. A total of 23270 mRNA expression and 1018 glioma samples were included in this study. After the three filtering analyses, we selected ten genes for immunohistochemical verification: KLHDC8A, IKIP, HIST1H2BK, HIST1H2BJ, GNG5, FAM114A1, TMEM71, RAB42, CCDC18, and GAS2L3. Immunostaining demonstrated that RAB42 was significantly expressed on the membrane of glioma tissues but not in normal tissues. These results were verified and validated in GEPIA datasets, and the association between RAB42 with clinical features was also evaluated. Analysis of gene functions indicated that RAB42 activated VEGF signaling pathways and the mechanism was associated with natural killer cell mediated cytotoxicity, JAK-STAT signaling pathway and apoptosis pathways by PI3K/AKT in gliomas. Experiments in vitro suggested that the proliferation and invasion of glioma cells might be inhibited after downregulating of RAB42. And the tumorigenesis promotion of RAB42 may relate to the activation of VEGF signaling pathway. Taken together, this study shows that the overexpression of RAB42 is an independent prognostic factor of adverse prognosis. Its pro-oncogenic mechanism may be associated with the activation of VEGF signaling pathways.
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Affiliation(s)
- Baoling Liu
- Central Laboratory, Key Laboratory of Tumor Biology, Key Laboratory of Neurophysiology, Linyi People's Hospital, Linyi, China
| | - Quanping Su
- Central Laboratory, Key Laboratory of Tumor Biology, Key Laboratory of Neurophysiology, Linyi People's Hospital, Linyi, China
| | - Bolian Xiao
- Central Laboratory, Key Laboratory of Tumor Biology, Key Laboratory of Neurophysiology, Linyi People's Hospital, Linyi, China
| | - Guodong Zheng
- Department of Neurosurgery, Linyi People's Hospital, Linyi, China
| | - Lizhong Zhang
- Neuropathological laboratory, Linyi People's Hospital, Linyi, China
| | - Jiawei Yin
- Central Laboratory, Key Laboratory of Tumor Biology, Key Laboratory of Neurophysiology, Linyi People's Hospital, Linyi, China
| | - Lijuan Wang
- Central Laboratory, Key Laboratory of Tumor Biology, Key Laboratory of Neurophysiology, Linyi People's Hospital, Linyi, China.,Department of Hematology, Linyi People's Hospital, Linyi, China
| | - Fengyuan Che
- Central Laboratory, Key Laboratory of Tumor Biology, Key Laboratory of Neurophysiology, Linyi People's Hospital, Linyi, China.,Department of Neurology, Linyi People's Hospital, Linyi, China
| | - Xueyuan Heng
- Department of Neurosurgery, Linyi People's Hospital, Linyi, China
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19
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Xi G, Qiu L, Xu S, Guo W, Fu F, Kang D, Zheng L, He J, Zhang Q, Li L, Wang C, Chen J. Computer-assisted quantification of tumor-associated collagen signatures to improve the prognosis prediction of breast cancer. BMC Med 2021; 19:273. [PMID: 34789257 PMCID: PMC8600902 DOI: 10.1186/s12916-021-02146-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 09/28/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Collagen fibers play an important role in tumor initiation, progression, and invasion. Our previous research has already shown that large-scale tumor-associated collagen signatures (TACS) are powerful prognostic biomarkers independent of clinicopathological factors in invasive breast cancer. However, they are observed on a macroscale and are more suitable for identifying high-risk patients. It is necessary to investigate the effect of the corresponding microscopic features of TACS so as to more accurately and comprehensively predict the prognosis of breast cancer patients. METHODS In this retrospective and multicenter study, we included 942 invasive breast cancer patients in both a training cohort (n = 355) and an internal validation cohort (n = 334) from one clinical center and in an external validation cohort (n = 253) from a different clinical center. TACS corresponding microscopic features (TCMFs) were firstly extracted from multiphoton images for each patient, and then least absolute shrinkage and selection operator (LASSO) regression was applied to select the most robust features to build a TCMF-score. Finally, the Cox proportional hazard regression analysis was used to evaluate the association of TCMF-score with disease-free survival (DFS). RESULTS TCMF-score is significantly associated with DFS in univariate Cox proportional hazard regression analysis. After adjusting for clinical variables by multivariate Cox regression analysis, the TCMF-score remains an independent prognostic indicator. Remarkably, the TCMF model performs better than the clinical (CLI) model in the three cohorts and is particularly outstanding in the ER-positive and lower-risk subgroups. By contrast, the TACS model is more suitable for the ER-negative and higher-risk subgroups. When the TACS and TCMF are combined, they could complement each other and perform well in all patients. As expected, the full model (CLI+TCMF+TACS) achieves the best performance (AUC 0.905, [0.873-0.938]; 0.896, [0.860-0.931]; 0.882, [0.840-0.925] in the three cohorts). CONCLUSION These results demonstrate that the TCMF-score is an independent prognostic factor for breast cancer, and the increased prognostic performance (TCMF+TACS-score) may help us develop more appropriate treatment protocols.
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Affiliation(s)
- Gangqin Xi
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, 350007, China
| | - Lida Qiu
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, 350007, China.,College of Physics and Electronic Information Engineering, Minjiang University, Fuzhou, 350108, China
| | - Shuoyu Xu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Wenhui Guo
- Breast Surgery Ward, Department of Breast Surgery, Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Fangmeng Fu
- Breast Surgery Ward, Department of Breast Surgery, Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Deyong Kang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Liqin Zheng
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, 350007, China
| | - Jiajia He
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, 350007, China
| | - Qingyuan Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Lianhuang Li
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, 350007, China.
| | - Chuan Wang
- Breast Surgery Ward, Department of Breast Surgery, Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
| | - Jianxin Chen
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, 350007, China.
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Chen R, Wang Y, Li T, Lv J, Feng G, Tan N, Wang J, Cheng X. Oncotype DX 21-gene test has a low recurrence score in both pure and mixed mucinous breast carcinoma. Oncol Lett 2021; 22:771. [PMID: 34589150 PMCID: PMC8442227 DOI: 10.3892/ol.2021.13032] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 07/23/2021] [Indexed: 11/23/2022] Open
Abstract
The Oncotype DX 21-gene test can be used to predict chemotherapy efficacy in patients with estrogen receptor (ER)-positive and HER2-negative breast cancer; however, the data on the 21-gene recurrence score (RS) for mucinous breast carcinoma (MBC) are limited. The present study aimed to evaluate the distribution pattern and clinical value of the 21-gene RS in patients with MBC. A total of 38 pure MBC (PMBC) and 11 mixed MBC (MMBC) cases were retrospectively analyzed, and a total of 29 ER-positive and HER2-negative MBCs underwent the Oncotype DX 21-gene test. There were no statistically significant differences between the PMBCs and MMBCs in age, tumor size and molecular subtype; however, patients with MMBC showed a significantly higher incidence rate of nodal metastases compared with that in patients with PMBC (72.7 vs. 16.2%, respectively). Following surgery, 87.8 and 59.2% of the enrolled patients received endocrine therapy and chemotherapy, respectively. With a median follow-up of 65.6 months, the 5-year disease-free survival and overall survival rates were 97.0 and 100.0%, respectively. The 21-gene test revealed that the proportions of patients with MBC categorized into low (RS <18), intermediate (RS ≥18-30) and high (RS ≥30) risk groups were 51.7, 44.8 and 3.5%, respectively, and there was no statistically significant difference between the PMBC and MMBC cases. Notably, among the genes in the 21-gene RS testing, the expression levels of cathepsin V, progesterone receptor (PR) and CD68 were significantly higher in the PMBC group compared with that in the MMBC group. In conclusion, the current study demonstrated that patients with MBC had a favorable prognosis, and both PMBC and MMBC cases had a low- and intermediate-risk RS, which suggests that a considerable proportion of patients may be able to avoid chemotherapy. In addition, the high expression level of PR, based on the 21-gene test in PMBCs, indicated that they may have a more favorable response to endocrine therapy than MMBCs.
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Affiliation(s)
- Rui Chen
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Yun Wang
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Taolang Li
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Junyuan Lv
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Guoli Feng
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Na Tan
- Department of Pathology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Jinjing Wang
- Department of Pathology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Xiaoming Cheng
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
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21
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Impact of the 21-Gene Recurrence Score Assay on the Treatment of Estrogen Receptor-Positive, HER2-Negative, Breast Cancer Patients With 1-3 Positive Nodes: A Prospective Clinical Utility Study. Clin Breast Cancer 2021; 22:e74-e79. [PMID: 34690081 DOI: 10.1016/j.clbc.2021.09.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 09/01/2021] [Accepted: 09/11/2021] [Indexed: 12/23/2022]
Abstract
PURPOSE The use of the 21-gene Recurrence Score (RS) assay is emerging in node-positive estrogen receptor (ER)+ HER2-negative breast cancer (BC), particularly as initial data from the RxPONDER trial are now available. We investigated the impact of the RS result on adjuvant treatment decisions in such patients. PATIENTS AND METHODS This prospective, multi-center study enrolled patients with ER+, HER2-negative BC and 1 to 3 positive nodes (microscopic [N1mi] or macroscopic [N1]). Treating oncologists documented treatment recommendations/plan before and after knowing the RS result. Sample size was determined assuming an overall treatment change rate (from chemohormonal therapy [CHT] to hormone therapy [HT] and vice-versa) of ≥30%. RESULTS The study included 84 patients across 5 regional cancer centers, of whom 82 underwent 21-gene testing (77%, N1 disease; 63% grade 2 tumors). Of the RS-tested patients, 60%, 33%, and 7% had RS 0 to 17, 18 to 30, and 31 to 100, respectively. In 43 patients (52%), treatment changed post-RS: 40 patients (49%) from CHT to HT and 3 patients (4%) from HT to CHT. The net change was a 45% reduction in chemotherapy use. Treatment recommendation changes were consistent with the RS result. In RS 0 to 17 patients, the only documented change was from CHT to HT (27 patients). In RS 18-30 patients, change was noted in both directions (CHT-to-HT, 13 patients; HT-to-CHT, 3 patients). No treatment change was reported for the RS 31 to 100 patients, all of whom were recommended CHT pre-testing. CONCLUSION Our results support the clinical utility of the RS assay in ER+ HER2-negative BC with 1 to 3 positive nodes.
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22
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Davey MG, Hynes SO, Kerin MJ, Miller N, Lowery AJ. Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer. Cancers (Basel) 2021; 13:4455. [PMID: 34503265 PMCID: PMC8430879 DOI: 10.3390/cancers13174455] [Citation(s) in RCA: 128] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/12/2022] Open
Abstract
The advent of molecular medicine has transformed breast cancer management. Breast cancer is now recognised as a heterogenous disease with varied morphology, molecular features, tumour behaviour, and response to therapeutic strategies. These parameters are underpinned by a combination of genomic and immunohistochemical tumour factors, with estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, Ki-67 proliferation indices, and multigene panels all playing a contributive role in the substratification, prognostication and personalization of treatment modalities for each case. The expression of Ki-67 is strongly linked to tumour cell proliferation and growth and is routinely evaluated as a proliferation marker. This review will discuss the clinical utility, current pitfalls, and promising strategies to augment Ki-67 proliferation indices in future breast oncology.
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Affiliation(s)
- Matthew G. Davey
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
- Department of Surgery, Galway University Hospitals, H91 YR71 Galway, Ireland
| | - Sean O. Hynes
- Department of Histopathology, National University of Ireland, H91 YR71 Galway, Ireland;
| | - Michael J. Kerin
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
| | - Nicola Miller
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
| | - Aoife J. Lowery
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
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23
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Barbi M, Makower D, Sparano JA. The clinical utility of gene expression assays in breast cancer patients with 0-3 involved lymph nodes. Ther Adv Med Oncol 2021; 13:17588359211038467. [PMID: 34408795 PMCID: PMC8366126 DOI: 10.1177/17588359211038467] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 07/22/2021] [Indexed: 12/14/2022] Open
Abstract
Multigene expression assays are prognostic for recurrence in hormone-receptor positive 2 (HER-2) negative breast cancer, and, in some cases, predictive of benefit from chemotherapy or extended endocrine therapy. The results of these assays may be used to guide treatment recommendations for early HER-2 negative breast cancer. We review the results of trials establishing the clinical utility of several commercially available gene expression assays.
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Affiliation(s)
- Mali Barbi
- Montefiore Einstein Center for Cancer Care, Bronx, NY, USA
| | - Della Makower
- Department of Oncology, Montefiore Medical Center, 1695 Eastchester Rd, Bronx, NY 10461, USA
| | - Joseph A Sparano
- Division of Hematology/Oncology, Mt. Sinai School of Medicine, New York, NY, USA
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Schaafsma E, Zhang B, Schaafsma M, Tong CY, Zhang L, Cheng C. Impact of Oncotype DX testing on ER+ breast cancer treatment and survival in the first decade of use. Breast Cancer Res 2021; 23:74. [PMID: 34274003 PMCID: PMC8285794 DOI: 10.1186/s13058-021-01453-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 07/08/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The Oncotype DX breast recurrence score has been introduced more than a decade ago to aid physicians in determining the need for systemic adjuvant chemotherapy in patients with early-stage, estrogen receptor (ER)+, lymph node-negative breast cancer. METHODS In this study, we utilized data from The Surveillance, Epidemiology, and End Results (SEER) Program to investigate temporal trends in Oncotype DX usage among US breast cancer patients in the first decade after the introduction of the Oncotype DX assay. RESULTS We found that the use of Oncotype DX has steadily increased in the first decade of use and that this increase is associated with a decreased usage of chemotherapy. Patients who utilized the Oncotype DX test tended to have improved survival compared to patients who did not use the assay even after adjusting for clinical variables associated with prognosis. In addition, chemotherapy usage in patients with high-risk scores is associated with significantly longer overall and breast cancer-specific survival compared to high-risk patients who did not receive chemotherapy. On the contrary, patients with low-risk scores who were treated with chemotherapy tended to have shorter overall survival compared to low-risk patients who forwent chemotherapy. CONCLUSION We have provided a comprehensive temporal overview of the use of Oncotype DX in breast cancer patients in the first decade after Oncotype DX was introduced. Our results suggest that the use of Oncotype DX is increasing in ER+ breast cancer and that the Oncotype DX test results provide valuable information for patient treatment and prognosis.
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Affiliation(s)
- Evelien Schaafsma
- Department of Molecular and Systems Biology, Dartmouth College, Hanover, NH, 03755, USA
| | - Baoyi Zhang
- Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77030, USA
| | - Merit Schaafsma
- Faculty of Medical Sciences, University of Groningen, Groningen, The Netherlands
| | - Chun-Yip Tong
- Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Lanjing Zhang
- Department of Biological Sciences, Rutgers University Newark, Newark, NJ, USA
- Department of Pathology, Princeton Medical Center, Plainsboro, NJ, USA
| | - Chao Cheng
- Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
- Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.
- The Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, 77030, USA.
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25
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Yu J, Lin C, Huang J, Hong J, Gao W, Zhu S, Lin L, Chen X, Huang O, He J, Zhu L, Chen W, Li Y, Wu J, Shen K. Efficacy of adjuvant chemotherapy stratified by age and the 21-gene recurrence score in estrogen receptor-positive breast cancer. BMC Cancer 2021; 21:707. [PMID: 34130640 PMCID: PMC8207606 DOI: 10.1186/s12885-021-08461-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 06/08/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively. METHODS Patients diagnosed with pN0-1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models. RESULTS A total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%). CONCLUSIONS Old patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.
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Affiliation(s)
- Jing Yu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Caijin Lin
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Jiahui Huang
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Jin Hong
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Weiqi Gao
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Siji Zhu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Lin Lin
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Xiaosong Chen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Ou Huang
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Jianrong He
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Li Zhu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Weiguo Chen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Yafen Li
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Jiayi Wu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Kunwei Shen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
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26
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Li Y, Bondarenko I, Elliott MR, Hofer TP, Taylor JM. Using multiple imputation to classify potential outcomes subgroups. Stat Methods Med Res 2021; 30:1428-1444. [PMID: 33884937 DOI: 10.1177/09622802211002866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
With medical tests becoming increasingly available, concerns about over-testing, over-treatment and health care cost dramatically increase. Hence, it is important to understand the influence of testing on treatment selection in general practice. Most statistical methods focus on average effects of testing on treatment decisions. However, this may be ill-advised, particularly for patient subgroups that tend not to benefit from such tests. Furthermore, missing data are common, representing large and often unaddressed threats to the validity of most statistical methods. Finally, it is often desirable to conduct analyses that can be interpreted causally. Using the Rubin Causal Model framework, we propose to classify patients into four potential outcomes subgroups, defined by whether or not a patient's treatment selection is changed by the test result and by the direction of how the test result changes treatment selection. This subgroup classification naturally captures the differential influence of medical testing on treatment selections for different patients, which can suggest targets to improve the utilization of medical tests. We can then examine patient characteristics associated with patient potential outcomes subgroup memberships. We used multiple imputation methods to simultaneously impute the missing potential outcomes as well as regular missing values. This approach can also provide estimates of many traditional causal quantities of interest. We find that explicitly incorporating causal inference assumptions into the multiple imputation process can improve the precision for some causal estimates of interest. We also find that bias can occur when the potential outcomes conditional independence assumption is violated; sensitivity analyses are proposed to assess the impact of this violation. We applied the proposed methods to examine the influence of 21-gene assay, the most commonly used genomic test in the United States, on chemotherapy selection among breast cancer patients.
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Affiliation(s)
- Yun Li
- Division of Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.,Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.,Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
| | - Irina Bondarenko
- Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
| | - Michael R Elliott
- Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.,Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
| | - Timothy P Hofer
- Division of General Medicine, University of Michigan, Ann Arbor, MI, USA.,VA Health Service Research & Development Center for Clinical Management Research, Ann Arbor, MI, USA
| | - Jeremy Mg Taylor
- Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
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27
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Arana Echarri A, Beresford M, Campbell JP, Jones RH, Butler R, Gollob KJ, Brum PC, Thompson D, Turner JE. A Phenomic Perspective on Factors Influencing Breast Cancer Treatment: Integrating Aging and Lifestyle in Blood and Tissue Biomarker Profiling. Front Immunol 2021; 11:616188. [PMID: 33597950 PMCID: PMC7882710 DOI: 10.3389/fimmu.2020.616188] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 12/11/2020] [Indexed: 01/10/2023] Open
Abstract
Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management.
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Affiliation(s)
| | - Mark Beresford
- Department of Oncology and Haematology, Royal United Hospitals Bath NHS Trust, Bath, United Kingdom
| | | | - Robert H. Jones
- Department of Medical Oncology, Velindre Cancer Centre, Cardiff, United Kingdom
- Department of Cancer and Genetics, Cardiff University, Cardiff, United Kingdom
| | - Rachel Butler
- South West Genomics Laboratory Hub, North Bristol NHS Trust, Bristol, United Kingdom
| | - Kenneth J. Gollob
- International Center for Research, A.C.Camargo Cancer Center, São Paulo, Brazil
| | - Patricia C. Brum
- School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil
| | - Dylan Thompson
- Department for Health, University of Bath, Bath, United Kingdom
| | - James E. Turner
- Department for Health, University of Bath, Bath, United Kingdom
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28
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Cheng R, Wang Z, Kong X, Wang J, Fang Y, Qi L. Factors associated with chemotherapy benefit in breast cancer patients with midrange Oncotype DX breast recurrence scores. Cancer Lett 2021; 503:213-219. [PMID: 33485948 DOI: 10.1016/j.canlet.2021.01.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/20/2020] [Accepted: 01/16/2021] [Indexed: 10/22/2022]
Abstract
Chemotherapy for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer, and with midrange Oncotype DX breast recurrence scores (RS) still needs to be further individualized. To improve the treatment decision making, we aimed to develop a method that provides a single score based on multiple factors associated with chemotherapy benefit. We analyzed Surveillance, Epidemiology, and End Results registry data from 31,731 patients with hormone receptor-positive, HER2-negative, node-negative breast cancer and midrange RS characterized by sociodemographic (age and marital status) and clinicopathologic (tumor size, histologic grade, progesterone receptor status, broad histological classification, lesion laterality, and lesion overlap) features and stratified by RS ranges. For the entire sample and for each characteristic, overall survival was compared between patients who underwent chemotherapy and those who did not (or status unknown) within each RS stratum. There was no any association between chemotherapy and survival for patients with RS = 11-15. However, for patients with RS = 16-25, a chemotherapy benefit was associated with tumor size, histologic grade, progesterone receptor status, histological type, and lesion laterality. In addition, overlapping lesion of breast and married at diagnosis might provide additional predictive information of chemotherapy benefit when RS = 21-25. A simple and effective algorithm was designed by combining these factors to output a novel and personalized chemotherapy benefit score to effectively identify patients with RS = 16-25 who would most likely benefit from chemotherapy, which might facilitate improved treatment by providing individualized recommendations.
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Affiliation(s)
- Ran Cheng
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhongzhao Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiangyi Kong
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jing Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Yi Fang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Liqiang Qi
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Factors That Predict Biological Aggressiveness in Estrogen Receptor-Positive / Human Epidermal Growth Factor Receptor 2-Negative / Lymph Node-Negative Breast Cancer. Ochsner J 2020; 20:381-387. [PMID: 33408575 PMCID: PMC7755554 DOI: 10.31486/toj.20.0035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: Traditionally, breast cancer is staged using TNM criteria: tumor size (T), nodal status (N), and metastasis (M). The Oncotype DX assay provides a recurrence score (RS) based on genomics that predicts the likelihood of distant recurrence in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2–)/lymph node–negative (LN–) tumors. Methods: We retrospectively reviewed the medical records of patients with ER+/HER2–/LN– breast cancer tumors who were evaluated between 2007 and 2017 with Oncotype DX RS. We compared the RS to tumor size, patient age, progesterone receptor (PR) status, and LN immunohistochemistry to assess for factors that may independently predict recurrence risk. We also compared tumor size to tumor grade. Results: The data set included 296 tumors: 248 ER+/PR-positive (PR+)/HER2– and 48 ER+/PR-negative (PR–)/HER2–. RS ranged from 0 to 66, patient age ranged from 33 to 77 years, and tumor size ranged from 1 to 65 mm. No significant correlation was found between age and RS (r=–0.073, P=0.208). PR– tumors had a significantly higher RS regardless of size (PR– mean RS 30.8 ± 12.7; PR+ mean RS 16.3 ± 7.3; t(53)=7.6, P<0.0001). No significant correlation was seen between tumor size and RS for all tumors (r=–0.028, P=0.635), and this finding remained true for the PR+ tumor subgroup (r=0.114, P=0.072). However, a significant negative correlation was seen between tumor size and RS in the PR– subgroup (r=–0.343, P=0.017). Further analysis to ensure that differences in tumor grade did not account for this correlation showed equal distribution of well differentiated, moderately differentiated, and poorly differentiated tumors with no significant correlation between tumor size and grade. Conclusion: Increasing tumor size may not be associated with increasing biological aggressiveness. Traditionally, smaller tumors are thought to be lower risk and larger tumors higher risk, with a tendency to use chemotherapy with large tumors. However, our data showed a negative correlation between tumor size and RS in the PR– subgroup. A tumor with PR negativity that reaches a large size without metastasizing may suggest a favorable tumor biology. These tumors may not receive as much benefit from chemotherapy as previously thought. Also, the higher RS seen in smaller PR– tumors may demonstrate PR– status as a predictor for higher risk of distant recurrence. We propose that all tumors meeting the ER+/PR–/LN– criteria, regardless of size, should be considered for genotyping, with the RS used to guide chemotherapy benefit.
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30
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Wu J, Gao W, Chen X, Fei C, Lin L, Chen W, Huang O, Zhu S, He J, Li Y, Zhu L, Shen K. Prognostic value of the 21-gene recurrence score in ER-positive, HER2-negative, node-positive breast cancer was similar in node-negative diseases: a single-center study of 800 patients. Front Med 2020; 15:621-628. [PMID: 33367943 DOI: 10.1007/s11684-020-0738-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Accepted: 11/27/2019] [Indexed: 11/25/2022]
Abstract
Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Among 800 patients recruited between 2009 and 2016, the median RS was 24 (0-69), with 27.4%, 46.8%, and 25.9% patients classified into low-, intermediate-, and high-risk groups. Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) events compared with the low-risk category (IDFS: HR = 2.450, 95% CI 1.017-5.902, P = 0.046; DDFS: HR = 2.829, 95% CI 1.013-7.901, P = 0.047). No significant association between RS category and overall survival (OS) was found (intermediate vs. low: HR= 1.244, 95% CI 0.292-5.297, P = 0.768; high vs. low: HR = 2.933, 95% CI 0.759-11.327, P = 0.119). RS, as a continuous variable, was a highly significant predictor for IDFS (HR= 1.028, 95% CI 1.010-1.047, P = 0.002), DDFS (HR= 1.030, 95% CI 1.010-1.051, P = 0.003), and OS (HR= 1.034, 95% CI 1.007-1.063, P = 0.014). Our findings suggested that RS may predict IDFS in Chinese patients with ER+/HER2- breast cancer with N0 or N1 disease.
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Affiliation(s)
- Jiayi Wu
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Weiqi Gao
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Xiaosong Chen
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Chunxiao Fei
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Lin Lin
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Weiguo Chen
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Ou Huang
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Siji Zhu
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jianrong He
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yafen Li
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Li Zhu
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Kunwei Shen
- Comprehensive Breast Health Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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Harnan S, Tappenden P, Cooper K, Stevens J, Bessey A, Rafia R, Ward S, Wong R, Stein RC, Brown J. Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis. Health Technol Assess 2020; 23:1-328. [PMID: 31264581 DOI: 10.3310/hta23300] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Breast cancer and its treatment can have an impact on health-related quality of life and survival. Tumour profiling tests aim to identify whether or not women need chemotherapy owing to their risk of relapse. OBJECTIVES To conduct a systematic review of the effectiveness and cost-effectiveness of the tumour profiling tests oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA), MammaPrint® (Agendia, Inc., Amsterdam, the Netherlands), Prosigna® (NanoString Technologies, Inc., Seattle, WA, USA), EndoPredict® (Myriad Genetics Ltd, London, UK) and immunohistochemistry 4 (IHC4). To develop a health economic model to assess the cost-effectiveness of these tests compared with clinical tools to guide the use of adjuvant chemotherapy in early-stage breast cancer from the perspective of the NHS and Personal Social Services. DESIGN A systematic review and health economic analysis were conducted. REVIEW METHODS The systematic review was partially an update of a 2013 review. Nine databases were searched in February 2017. The review included studies assessing clinical effectiveness in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I or II cancer with zero to three positive lymph nodes. The economic analysis included a review of existing analyses and the development of a de novo model. RESULTS A total of 153 studies were identified. Only one completed randomised controlled trial (RCT) using a tumour profiling test in clinical practice was identified: Microarray In Node-negative Disease may Avoid ChemoTherapy (MINDACT) for MammaPrint. Other studies suggest that all the tests can provide information on the risk of relapse; however, results were more varied in lymph node-positive (LN+) patients than in lymph node-negative (LN0) patients. There is limited and varying evidence that oncotype DX and MammaPrint can predict benefit from chemotherapy. The net change in the percentage of patients with a chemotherapy recommendation or decision pre/post test ranged from an increase of 1% to a decrease of 23% among UK studies and a decrease of 0% to 64% across European studies. The health economic analysis suggests that the incremental cost-effectiveness ratios for the tests versus current practice are broadly favourable for the following scenarios: (1) oncotype DX, for the LN0 subgroup with a Nottingham Prognostic Index (NPI) of > 3.4 and the one to three positive lymph nodes (LN1-3) subgroup (if a predictive benefit is assumed); (2) IHC4 plus clinical factors (IHC4+C), for all patient subgroups; (3) Prosigna, for the LN0 subgroup with a NPI of > 3.4 and the LN1-3 subgroup; (4) EndoPredict Clinical, for the LN1-3 subgroup only; and (5) MammaPrint, for no subgroups. LIMITATIONS There was only one completed RCT using a tumour profiling test in clinical practice. Except for oncotype DX in the LN0 group with a NPI score of > 3.4 (clinical intermediate risk), evidence surrounding pre- and post-test chemotherapy probabilities is subject to considerable uncertainty. There is uncertainty regarding whether or not oncotype DX and MammaPrint are predictive of chemotherapy benefit. The MammaPrint analysis uses a different data source to the other four tests. The Translational substudy of the Arimidex, Tamoxifen, Alone or in Combination (TransATAC) study (used in the economic modelling) has a number of limitations. CONCLUSIONS The review suggests that all the tests can provide prognostic information on the risk of relapse; results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence that oncotype DX and MammaPrint are predictive of chemotherapy benefit. Health economic analyses indicate that some tests may have a favourable cost-effectiveness profile for certain patient subgroups; all estimates are subject to uncertainty. More evidence is needed on the prediction of chemotherapy benefit, long-term impacts and changes in UK pre-/post-chemotherapy decisions. STUDY REGISTRATION This study is registered as PROSPERO CRD42017059561. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Sue Harnan
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Paul Tappenden
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Katy Cooper
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - John Stevens
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Alice Bessey
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Rachid Rafia
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Sue Ward
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Ruth Wong
- Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Robert C Stein
- University College London Hospitals Biomedical Research Centre, London, UK.,Research Department of Oncology, University College London, London, UK
| | - Janet Brown
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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32
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Yu F, Quan F, Xu J, Zhang Y, Xie Y, Zhang J, Lan Y, Yuan H, Zhang H, Cheng S, Xiao Y, Li X. Breast cancer prognosis signature: linking risk stratification to disease subtypes. Brief Bioinform 2020; 20:2130-2140. [PMID: 30184043 DOI: 10.1093/bib/bby073] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Revised: 07/14/2018] [Accepted: 07/28/2018] [Indexed: 01/29/2023] Open
Abstract
Breast cancer is a very complex and heterogeneous disease with variable molecular mechanisms of carcinogenesis and clinical behaviors. The identification of prognostic risk factors may enable effective diagnosis and treatment of breast cancer. In particular, numerous gene-expression-based prognostic signatures were developed and some of them have already been applied into clinical trials and practice. In this study, we summarized several representative gene-expression-based signatures with significant prognostic value and separately assessed their ability of prognosis prediction in their originally targeted populations of breast cancer. Notably, many of the collected signatures were originally designed to predict the outcomes of estrogen receptor positive (ER+) patients or the whole breast cancer cohort; there are no typical signatures used for the prognostic prediction in a specific population of patients with the intrinsic subtype. We thus attempted to identify subtype-specific prognostic signatures via a computational framework for analyzing multi-omics profiles and patient survival. For both the discovery and an independent data set, we confirmed that subtype-specific signature is a strong and significant independent prognostic factor in the corresponding cohort. These results indicate that the subtype-specific prognostic signature has a much higher resolution in the risk stratification, which may lead to improved therapies and precision medicine for patients with breast cancer.
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Affiliation(s)
- Fulong Yu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Fei Quan
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Jinyuan Xu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Yan Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Yi Xie
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Jingyu Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Yujia Lan
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Huating Yuan
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Hongyi Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Shujun Cheng
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.,State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China
| | - Yun Xiao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Xia Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China
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Caputo R, Cianniello D, Giordano A, Piezzo M, Riemma M, Trovò M, Berretta M, De Laurentiis M. Gene Expression Assay in the Management of Early Breast Cancer. Curr Med Chem 2020; 27:2826-2839. [PMID: 31804159 DOI: 10.2174/0929867326666191205163329] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 11/14/2019] [Accepted: 11/22/2019] [Indexed: 01/21/2023]
Abstract
The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of the patients could be exposed to unnecessary treatment- related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician's decision-making process and to tailor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay).
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Affiliation(s)
- Roberta Caputo
- Division of Breast Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale", Napoli, Italy
| | - Daniela Cianniello
- Division of Breast Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale", Napoli, Italy
| | - Antonio Giordano
- Division of Hematology/Oncology, Medical University of South Carolina, Charleston, SC, United States
| | - Michela Piezzo
- Division of Breast Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale", Napoli, Italy
| | - Maria Riemma
- Division of Breast Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale", Napoli, Italy
| | - Marco Trovò
- Division of Radiation Oncology, Centro di Riferimento Oncologico - CRO, Aviano, Italy
| | | | - Michelino De Laurentiis
- Division of Breast Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale", Napoli, Italy
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34
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Yu J, Wu J, Huang O, He J, Zhu L, Chen W, Li Y, Chen X, Shen K. Clinicopathological characteristics, adjuvant chemotherapy decision and disease outcome in patients with breast cancer with a 21-gene recurrence score of 26-30. Oncol Lett 2020; 20:1545-1556. [PMID: 32724396 PMCID: PMC7377026 DOI: 10.3892/ol.2020.11734] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 03/26/2020] [Indexed: 12/19/2022] Open
Abstract
Recurrence score (RS) could be used to predict clinical outcomes and chemotherapy efficacy in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. However, the clinical features and management of patients with an RS of 26–30 are not completely understood. In the present study, 783 patients with HR+/HER2−, lymph node-negative early breast cancer and RS ≥18 were included and categorized into RS=18−25 (47.8%), 26–30 (25.5%) or ≥31 (26.7%) groups. Clinicopathological characteristics, adjuvant chemotherapy usage and disease outcomes were compared. Alterations in the adjuvant chemotherapy recommendation after 21-gene RS testing were also analyzed. The results indicated that patients with RS=26−30 had higher progesterone receptor (PR) expression [odds ratio (OR)=2.84; P<0.001] and lower Ki-67 index (OR, 1.88; P=0.032) compared with patients with RS ≥31. Multivariate analysis demonstrated that age ≤50 years (OR, 5.75; P=0.001) and luminal-B subtype (OR, 7.75; P<0.001) were factors that were independently associated with chemotherapy usage in the RS=26−30 group. Among 104 patients who were not recommended chemotherapy before 21-gene RS testing, the treatment decision for 52 patients was changed to recommend chemotherapy once an RS of 26–30 was identified. The patient adherence rate to the treatment recommendation was 95.0% (190/200). After a median follow-up of 21.5 months, 6 patients displayed disease recurrence in the RS=26−30 group, and there was no significant difference between patients receiving chemotherapy and patients not receiving chemotherapy. In conclusion, patients with RS=26−30 had tumors with higher PR expression and lower Ki-67 index compared with those of patients with RS ≥31. Age, luminal subtype and RS testing influenced chemotherapy usage in patients with RS=26−30; however, no significant benefit from adjuvant chemotherapy was observed in a short term of 2 years.
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Affiliation(s)
- Jing Yu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Jiayi Wu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Ou Huang
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Jianrong He
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Li Zhu
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Weiguo Chen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Yafen Li
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Xiaosong Chen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Kunwei Shen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
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35
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Salvucci M, Rahman A, Resler AJ, Udupi GM, McNamara DA, Kay EW, Laurent-Puig P, Longley DB, Johnston PG, Lawler M, Wilson R, Salto-Tellez M, Van Schaeybroeck S, Rafferty M, Gallagher WM, Rehm M, Prehn JHM. A Machine Learning Platform to Optimize the Translation of Personalized Network Models to the Clinic. JCO Clin Cancer Inform 2020; 3:1-17. [PMID: 30995124 DOI: 10.1200/cci.18.00056] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Dynamic network models predict clinical prognosis and inform therapeutic intervention by elucidating disease-driven aberrations at the systems level. However, the personalization of model predictions requires the profiling of multiple model inputs, which hampers clinical translation. PATIENTS AND METHODS We applied APOPTO-CELL, a prognostic model of apoptosis signaling, to showcase the establishment of computational platforms that require a reduced set of inputs. We designed two distinct and complementary pipelines: a probabilistic approach to exploit a consistent subpanel of inputs across the whole cohort (Ensemble) and a machine learning approach to identify a reduced protein set tailored for individual patients (Tree). Development was performed on a virtual cohort of 3,200,000 patients, with inputs estimated from clinically relevant protein profiles. Validation was carried out in an in-house stage III colorectal cancer cohort, with inputs profiled in surgical resections by reverse phase protein array (n = 120) and/or immunohistochemistry (n = 117). RESULTS Ensemble and Tree reproduced APOPTO-CELL predictions in the virtual patient cohort with 92% and 99% accuracy while decreasing the number of inputs to a consistent subset of three proteins (40% reduction) or a personalized subset of 2.7 proteins on average (46% reduction), respectively. Ensemble and Tree retained prognostic utility in the in-house colorectal cancer cohort. The association between the Ensemble accuracy and prognostic value (Spearman ρ = 0.43; P = .02) provided a rationale to optimize the input composition for specific clinical settings. Comparison between profiling by reverse phase protein array (gold standard) and immunohistochemistry (clinical routine) revealed that the latter is a suitable technology to quantify model inputs. CONCLUSION This study provides a generalizable framework to optimize the development of network-based prognostic assays and, ultimately, to facilitate their integration in the routine clinical workflow.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Mark Lawler
- Queen's University Belfast, Belfast, United Kingdom
| | | | | | | | | | | | - Markus Rehm
- Royal College of Surgeons in Ireland, Dublin, Ireland.,University of Stuttgart, Stuttgart, Germany
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36
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Harmonizing gene signatures to predict benefit from adjuvant chemotherapy in early breast cancer. Curr Opin Oncol 2020; 31:472-479. [PMID: 31593974 DOI: 10.1097/cco.0000000000000570] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW Breast cancer is a heterogeneous disease, including different subtypes with their own biology, prognosis, clinical characteristics and treatment. To date, traditional clinical and pathological determinants remain the main factors guiding treatment decision-making; however, the development of multigene assays improved the ability to predict the risk of recurrence in patients with early-stage breast cancer. These tools underwent an extensive independent validation and have already been partly incorporated into clinical practice. RECENT FINDINGS The current article summarizes current evidence for the use of the different genomic assays in clinical practice, their characteristics and validation studies. A few studies comparing available genomic assays revealed that they provide different information with a modest correlation and that they are not interchangeable; other trials are currently ongoing in this setting. SUMMARY Variability across different gene signatures may be a challenge for the optimal management of the individual patient, hence each assay should be used for the clinical setting in which it has been validated.
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Hillyar C, Rizki H, Abbassi O, Miles-Dua S, Clayton G, Gandamihardja T, Smith S. Correlation Between Oncotype DX, PREDICT and the Nottingham Prognostic Index: Implications for the Management of Early Breast Cancer. Cureus 2020; 12:e7552. [PMID: 32382456 PMCID: PMC7202586 DOI: 10.7759/cureus.7552] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 04/05/2020] [Indexed: 12/28/2022] Open
Abstract
Introduction Breast cancer remains the most common cancer diagnosis in the UK. The current clinical practice utilises two different types of modalities to estimate the prognosis, risk of recurrence and benefit from adjuvant chemotherapy treatment in patients with early breast cancer. The first set of modalities includes risk calculators based on clinicopathological features, e.g. PREDICT or the Nottingham Prognostic Index (NPI); the second includes genetic profiling of tumour tissue using Oncotype DX (ODX; Genomic Health, Redwood City, CA) testing. PREDICT, NPI and ODX stratify breast cancers into high-, intermediate- and low-risk categories to help guide adjuvant chemotherapy treatment decisions. This study compares PREDICT, NPI and ODX Recurrence Scores (RS), with the aim of assessing 1) the correlation between the RS for PREDICT, NPI and ODX and 2) whether early breast cancer patients are stratified into similar risk categories by all three modalities. Methods This retrospective study included early breast cancer patients treated at a National Health Service (NHS) hospital over a 12-month period (October 1, 2017 to September 30, 2018). Inclusion criteria: consecutive patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. All patients were discussed at the local multidisciplinary team (MDT) meeting and underwent ODX testing. Exclusion criteria: patients without ODX test scores; patients with an in-breast recurrence; patients who did not undergo a sentinel lymph node biopsy (SLNB); and patients with ductal carcinoma in situ (DCIS) only. NPI and PREDICT scores were calculated for each patient using online tools, and ODX data was obtained through Genomic Health and MDT records. Patients were risk-stratified into high, intermediate and low risk of recurrence groups based on their PREDICT, NPI and ODX scores. The thresholds for risk stratification were based on current practice, which is evidence-based. Correlations between PREDICT, NPI and ODX scores were analysed using Spearman's correlation coefficient. Results Forty-six patients (mean age: 56 years), with a total of 57 early breast cancers, underwent ODX testing. Risk categories generated by PREDICT very strongly correlated with NPI for all patients (r=0.92; P<0.0001). However, the RS generated by ODX testing only strongly correlated for patients with low-risk PREDICT scores (r=0.51; P=0.0134), while no correlation between RS and PREDICT was observed for patients with intermediate- or high-risk PREDICT scores (r=-0.0064; P=0.9767). Similar results were seen between NPI and RS. Overall, only 19/46 (41.3%) patients had an RS which corresponded to PREDICT risk category, while 18/46 (39.1%) patients had an RS that indicated a higher risk of recurrence than PREDICT, and 9/46 (19.6%) patients had an RS indicating a lower risk of recurrence than PREDICT. Similar results were found when comparing RS and NPI. Conclusion The risk of recurrence estimated by ODX in patients deemed low risk by PREDICT or NPI highly correlated, while no such correlation existed in patients with an estimated intermediate- or high-risk breast cancer. In PREDICT- or NPI-estimated intermediate- and high-risk patients, ODX provided valuable additional prognostic information to guide adjuvant treatment, while the potential avoidance of ODX testing in low-risk patients presents significant cost-savings.
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Affiliation(s)
- Christopher Hillyar
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, GBR
| | - Hirah Rizki
- Chelmsford Breast Unit, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
| | - Omar Abbassi
- Surgery, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
| | - Sascha Miles-Dua
- Chelmsford Breast Unit, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
| | - Gillian Clayton
- Chelmsford Breast Unit, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
| | - Tasha Gandamihardja
- Chelmsford Breast Unit, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
| | - Simon Smith
- Chelmsford Breast Unit, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
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38
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Rizki H, Hillyar C, Abbassi O, Miles-Dua S. The Utility of Oncotype DX for Adjuvant Chemotherapy Treatment Decisions in Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative, Node-negative Breast Cancer. Cureus 2020; 12:e7269. [PMID: 32195072 PMCID: PMC7075474 DOI: 10.7759/cureus.7269] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 03/14/2020] [Indexed: 01/22/2023] Open
Abstract
Introduction Breast cancer is the most common cancer diagnosis in the UK. Recently, there has been a reduction in breast cancer-specific mortality and recurrence attributed, in part, to the delivery of adjuvant chemotherapy. The National Institute for Health and Care Excellence (NICE) recommends the use of genetic profiling with Oncotype DX (ODX) to guide decisions to offer adjuvant chemotherapy after surgery in intermediate-risk early breast cancer patients. This study aimed to evaluate the utility of ODX testing in routine clinical practice in a National Health Service (NHS) hospital. Methods Consecutive early breast cancer patients, identified through the multidisciplinary team (MDT) records, treated in our institution over 12 months (October 2017-September 2018) were included. PREDICT and Nottingham prognostic index (NPI) scores (from online clinicopathological recurrence risk tools) were calculated for each patient, and ODX data obtained through Genomic Health, Inc. (Redwood City, California). Patients were divided into two groups, those that underwent ODX testing (ODX group) and those that did not (non-ODX group). Descriptive statistics were used to analyse patient and tumour characteristics. The Gaussian distribution of each data set was assessed using the Anderson-Darling test. For comparisons between patient groups, the non-parametric equivalent of the two-tailed t-test (Mann-Whitney) was used. Dichotomous variables (e.g. chemotherapy decisions) were compared using chi-squared tests. Results One-hundred thirty-three patients (mean age 62 years) treated for 152 early breast cancers, were included in the final analysis. Breast cancers in the ODX group were of greater median tumour size (24 vs 16 mm; P<0.0001) and higher median tumour grade (3 vs 2; P<0.0001). PREDICT scores (3 vs 1, P<0.0001) and NPI scores (3.40 vs 2.30, P<0.0001) for the ODX group were also significantly higher than the non-ODX group. A greater proportion of patients were offered chemotherapy in the ODX group (39.9% vs 6.9%, P<0.001). However, for the PREDICT-calculated intermediate-risk patients, ODX testing resulted in a lower proportion of patients being offered chemotherapy compared to the intermediate-risk patients who were not genetically profiled (54.5% vs 83.3%, P=0.3547), although this result was not statistically significant. Conclusions Patients selected for ODX testing were younger, with significantly higher-grade and larger-sized tumours compared to patients not selected for genetic profiling. ODX testing significantly impacted the delivery of chemotherapy, as the recurrence score generated through ODX testing guided the final decision.
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Affiliation(s)
- Hirah Rizki
- Breast Surgery, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
| | | | - Omar Abbassi
- Surgery, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
| | - Sascha Miles-Dua
- Surgery, Mid Essex Hospitals National Health Service (NHS) Trust, Broomfield, GBR
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Advances in molecular mechanisms of drugs affecting abnormal glycosylation and metastasis of breast cancer. Pharmacol Res 2020; 155:104738. [PMID: 32151681 DOI: 10.1016/j.phrs.2020.104738] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/28/2020] [Accepted: 02/28/2020] [Indexed: 12/27/2022]
Abstract
Breast cancer remains the leading cause of cancer-related death among women worldwide, and its incidence is also increasing. High recurrence rate and metastasis rate are the key causes of poor prognosis and death. It is suggested that abnormal glycosylation plays an important role in the growth, invasion, metastasis and resistance to therapy of breast cancer cells. Meanwhile, it can be used as the biomarkers for the early detection and prognosis of breast cancer and the potential attractive targets for drug treatment. However, only a few attentions have been paid to the molecular mechanism of abnormal glycosylation in the epithelial-mesenchymal transition (EMT) of breast cancer cells and the related intervention of drugs. This manuscript thus investigated the relationship between abnormal glycosylation, the EMT, and breast cancer metastasis. Then, the process of abnormal glycosylation, the classification and their molecular regulatory mechanisms of breast cancer were analyzed in detail. Last, potential drugs are introduced in different categories, which are expected to reverse or intervene the abnormal glycosylation of breast cancer. This review is conducive to an in-depth understanding of the metastasis and drug resistance of breast cancer cells, which will provide new ideas for the clinical regulation of glycosylation and related drug treatments in breast cancer.
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Giardiello D, Steyerberg EW, Hauptmann M, Adank MA, Akdeniz D, Blomqvist C, Bojesen SE, Bolla MK, Brinkhuis M, Chang-Claude J, Czene K, Devilee P, Dunning AM, Easton DF, Eccles DM, Fasching PA, Figueroa J, Flyger H, García-Closas M, Haeberle L, Haiman CA, Hall P, Hamann U, Hopper JL, Jager A, Jakubowska A, Jung A, Keeman R, Kramer I, Lambrechts D, Le Marchand L, Lindblom A, Lubiński J, Manoochehri M, Mariani L, Nevanlinna H, Oldenburg HSA, Pelders S, Pharoah PDP, Shah M, Siesling S, Smit VTHBM, Southey MC, Tapper WJ, Tollenaar RAEM, van den Broek AJ, van Deurzen CHM, van Leeuwen FE, van Ongeval C, Van't Veer LJ, Wang Q, Wendt C, Westenend PJ, Hooning MJ, Schmidt MK. Prediction and clinical utility of a contralateral breast cancer risk model. Breast Cancer Res 2019; 21:144. [PMID: 31847907 PMCID: PMC6918633 DOI: 10.1186/s13058-019-1221-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 10/29/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. METHODS We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. RESULTS In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was -0.13 (95% PI: -1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS We developed a reasonably calibrated model to predict the risk of CBC in women of European-descent; however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision-making regarding contralateral preventive mastectomy, especially in the general breast cancer population where limited information of the mutation status in BRCA1/2 is available, remains challenging.
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Affiliation(s)
- Daniele Giardiello
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Ewout W Steyerberg
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
- Department of Public Health, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Michael Hauptmann
- Institute of Biometry and Registry Research, Brandenburg Medical School, Neuruppin, Germany
- Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Muriel A Adank
- The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Family Cancer Clinic, Amsterdam, The Netherlands
| | - Delal Akdeniz
- Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Carl Blomqvist
- Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- Department of Oncology, Örebro University Hospital, Örebro, Sweden
| | - Stig E Bojesen
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Manjeet K Bolla
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Mariël Brinkhuis
- East-Netherlands, Laboratory for Pathology, Hengelo, The Netherlands
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Peter Devilee
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
| | - Alison M Dunning
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Douglas F Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Diana M Eccles
- Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Peter A Fasching
- Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
| | - Jonine Figueroa
- Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK
- Cancer Research UK Edinburgh Centre, Edinburgh, UK
- Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Henrik Flyger
- Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
| | - Montserrat García-Closas
- Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK
| | - Lothar Haeberle
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
| | - Christopher A Haiman
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Per Hall
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- Department of Oncology, Södersjukhuset, Stockholm, Sweden
| | - Ute Hamann
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - John L Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Agnes Jager
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
- Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland
| | - Audrey Jung
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Renske Keeman
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Iris Kramer
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Diether Lambrechts
- VIB Center for Cancer Biology, VIB, Leuven, Belgium
- Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium
| | - Loic Le Marchand
- University of Hawaii Cancer Center, Epidemiology Program, Honolulu, HI, USA
| | - Annika Lindblom
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
| | - Jan Lubiński
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
| | - Mehdi Manoochehri
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Luigi Mariani
- Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Heli Nevanlinna
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Hester S A Oldenburg
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Saskia Pelders
- Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Paul D P Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Mitul Shah
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Sabine Siesling
- Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands
| | - Vincent T H B M Smit
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - Melissa C Southey
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
- Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
| | | | - Rob A E M Tollenaar
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Alexandra J van den Broek
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | | | - Flora E van Leeuwen
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands
| | - Chantal van Ongeval
- Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
| | - Laura J Van't Veer
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Qin Wang
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Camilla Wendt
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | | | - Maartje J Hooning
- Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Marjanka K Schmidt
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.
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Alexandre M, Maran-Gonzalez A, Viala M, Firmin N, D'Hondt V, Gutowski M, Bourgier C, Jacot W, Guiu S. Decision of Adjuvant Systemic Treatment in HR+ HER2- Early Invasive Breast Cancer: Which Biomarkers Could Help? Cancer Manag Res 2019; 11:10353-10373. [PMID: 31849525 PMCID: PMC6912012 DOI: 10.2147/cmar.s221676] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 09/21/2019] [Indexed: 11/23/2022] Open
Abstract
The decision to administer adjuvant chemotherapy in treatment of early invasive breast cancer (EBC) is often complex, particularly for hormone receptor-positive (HR+) diseases, and current guidelines often classify these patients in an intermediate-risk group. Several biomarkers are currently available in this indication, in order to obtain additional and more accurate prognostic information compared to classic clinicopathological characteristics and guide the indication of adjuvant chemotherapy, optimizing the efficacy/toxicity ratio. We conducted a systematic review to evaluate the clinical validity and clinical utility of five biomarkers (uPA/PAI-1, OncotypeDX®, MammaPrint®, PAM50, and EndoPredict®) in HR+/HER2- EBC, whatever the nodal status. A total of 89 studies met the inclusion criteria. Even though data currently available confirm the clinical validity of these biomarkers, there is a lack of data regarding clinical utility for most of them. Prospective studies in well-defined populations are needed to integrate these biomarkers in a decision strategy.
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Affiliation(s)
- Marie Alexandre
- Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France
| | - Aurélie Maran-Gonzalez
- Department of Pathology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France
| | - Marie Viala
- Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France
| | - Nelly Firmin
- Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France
| | - Véronique D'Hondt
- Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France.,INSERM U1194 - Institut de Recherche en Cancérologie de Montpellier (IRCM), Montpellier, France.,University of Montpellier, Montpellier,France
| | - Marian Gutowski
- Department of Surgery, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France
| | - Céline Bourgier
- INSERM U1194 - Institut de Recherche en Cancérologie de Montpellier (IRCM), Montpellier, France.,Department of Radiation Oncology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France
| | - William Jacot
- Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France.,INSERM U1194 - Institut de Recherche en Cancérologie de Montpellier (IRCM), Montpellier, France.,University of Montpellier, Montpellier,France
| | - Séverine Guiu
- Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Montpellier Cedex 5 34298, France.,INSERM U1194 - Institut de Recherche en Cancérologie de Montpellier (IRCM), Montpellier, France.,University of Montpellier, Montpellier,France
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Tong Y, Wu J, Huang O, He J, Zhu L, Chen W, Li Y, Chen X, Shen K. 21-Gene Recurrence Score and Adjuvant Chemotherapy Decision for Breast Cancer Patients with Positive Lymph Nodes. Sci Rep 2019; 9:13123. [PMID: 31511599 PMCID: PMC6739381 DOI: 10.1038/s41598-019-49644-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 08/27/2019] [Indexed: 01/04/2023] Open
Abstract
The 21-gene recurrence score (RS) assay is prognostic and predictive for hormone receptor (HR)+/HER2-/node- breast cancer (BC) patients. However, its clinical value in node + patients hasn’t been elucidated. HR+/HER2-/pN1 patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital from January 2014 to December 2018, with available RS results were retrospectively included. Clinico-pathological characteristics were compared. Adjuvant chemotherapy recommendations pre-/post- RS assay and actual usage were analyzed. A total of 303 patients were included, with 59, 178, 66 RS < 18, 18–30 and ≥ 31. Age (P < 0.001), comorbidity (P = 0.013), and RS category (P < 0.001) were independently associated with chemotherapy recommendation. Compared with low RS patients, those with intermediate (OR 6.58, 95% CI 2.37–18.31, P < 0.001) or high (OR 54.14, 95% CI 3.77–776.54, P = 0.003) RS were more likely to be recommended with chemotherapy. RS independently influence chemotherapy decision in postmenopausal population as well. Chemotherapy recommendation changed for 9.57% patients after RS assay. Patient adherence rate to chemotherapy recommendation was 94.72% (287/303). The 21-gene RS independently influenced chemotherapy recommendation in pN1 BC patients, which could provide additional information to guide chemotherapy decision with relatively good treatment adherence rate.
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Affiliation(s)
- Yiwei Tong
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiayi Wu
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ou Huang
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianrong He
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Zhu
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiguo Chen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yafen Li
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaosong Chen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Kunwei Shen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Scott DA, Drake RR. Glycosylation and its implications in breast cancer. Expert Rev Proteomics 2019; 16:665-680. [PMID: 31314995 PMCID: PMC6702063 DOI: 10.1080/14789450.2019.1645604] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 07/15/2019] [Indexed: 02/07/2023]
Abstract
Introduction: For decades, the role of glycans and glycoproteins in the progression of breast cancer and other cancers have been evaluated. Through extensive studies focused on elucidating the biological functions of glycosylation, researchers have been able to implicate alterations in these functions to tumor formation and metastasis. Areas covered: In this review, we summarize how changes in glycosylation are associated with tumorigenesis, with emphasis on breast cancers. An overview of the changes in N-linked and O-linked glycans associated with breast cancer tumors and biofluids are described. Recent advances in glycomics are emphasized in the context of continuing to decipher the glycosylation changes associated with breast cancer progression. Expert opinion: While changes in glycosylation have been studied in breast cancer for many years, the clinical relevance of these studies has been limited. This reflects the inherent biological and clinical heterogeneity of breast cancers. Glycomics analysis lags behind the advances in genomics and proteomics, but new approaches are emerging. A summary of known glycosylation changes associated with breast cancer is necessary to implement new findings in the context of clinical outcomes and therapeutic strategies. A better understanding of the dynamics of tumor and immune glycosylation is critical to improving emerging immunotherapeutic treatments.
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Affiliation(s)
- Danielle A Scott
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics and MUSC, Proteomics Center, Medical University of South Carolina , Charleston , SC , USA
| | - Richard R Drake
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics and MUSC, Proteomics Center, Medical University of South Carolina , Charleston , SC , USA
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Sparano JA, Gray R. TAILORx: Questions Answered, Lessons Learned, and Remaining Knowledge Gaps. J Clin Oncol 2019; 37:1841-1842. [PMID: 31173552 PMCID: PMC6881095 DOI: 10.1200/jco.19.00828] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Joseph A. Sparano
- Joseph A. Sparano, MD, Montefiore Hospital and Medical Center, Bronx, NY; and Robert Gray, PhD, Dana-Farber Cancer Institute, Boston, MA
| | - Robert Gray
- Joseph A. Sparano, MD, Montefiore Hospital and Medical Center, Bronx, NY; and Robert Gray, PhD, Dana-Farber Cancer Institute, Boston, MA
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Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE, Dees EC, Goetz MP, Olson JA, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med 2019; 380:2395-2405. [PMID: 31157962 PMCID: PMC6709671 DOI: 10.1056/nejmoa1904819] [Citation(s) in RCA: 350] [Impact Index Per Article: 58.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).
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Affiliation(s)
- Joseph A Sparano
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Robert J Gray
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Peter M Ravdin
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Della F Makower
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Kathleen I Pritchard
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Kathy S Albain
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Daniel F Hayes
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Charles E Geyer
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Elizabeth C Dees
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Matthew P Goetz
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - John A Olson
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Tracy Lively
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Sunil S Badve
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Thomas J Saphner
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Lynne I Wagner
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Timothy J Whelan
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Matthew J Ellis
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Soonmyung Paik
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - William C Wood
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Maccon M Keane
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Henry L Gomez Moreno
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Pavan S Reddy
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Timothy F Goggins
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Ingrid A Mayer
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Adam M Brufsky
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Deborah L Toppmeyer
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Virginia G Kaklamani
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Jeffrey L Berenberg
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - Jeffrey Abrams
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
| | - George W Sledge
- From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), and Duke University Medical Center, Durham (J.A.O., J.A.) - both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.)
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Ding S, Wu J, Lin C, Andriani L, Goh C, Chen W, Li Y, Shen K, Zhu L. Evaluation of the Incorporation of Recurrence Score into the American Joint Committee on Cancer Eighth Edition Staging System in Patients with T1-2N0M0, Estrogen Receptor-Positive, Human Epidermal Growth Receptor 2-Negative Invasive Breast Cancer: A Population-Based Analysis. Oncologist 2019; 24:e1014-e1023. [PMID: 31019021 DOI: 10.1634/theoncologist.2018-0727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 04/02/2019] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND The current study aimed to evaluate the predictive performance of the American Joint Committee on Cancer eighth edition staging system in patients with invasive breast cancer based on the Surveillance, Epidemiology, and End Results database. SUBJECTS, MATERIALS, AND METHODS Patients diagnosed with T1-2N0M0, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer from 2010 to 2014 were retrospectively recruited in this analysis. Patients were reassigned to different stages according to the anatomic staging system (AS), prognostic staging system (PS), and prognostic and genomic staging criteria downstaging patients with recurrence score (RS) lower than 11 (PGS_RS11). Cox models were conducted for multivariate analyses, and likelihood ratio (LR) χ2, Akaike information criterion (AIC), and Harrell's concordance index (C-index) were calculated for the comparison of different staging systems. Additionally, adjustments were made to generate prognostic and genomic staging criteria downstaging patients with RS lower than 18 (PGS_RS18) and RS lower than 25 (PGS_RS25). RESULTS PGS_RS11 was an independent predictor for breast cancer-specific survival, as were PS and AS. Adjusted for age and ethnicity, PGS_RS11 (AIC = 2,322.763, C-index = 0.7482, LR χ2 = 113.17) showed superiority in predicting survival outcomes and discriminating patients compared with AS (AIC = 2,369.132, C-index = 0.6986, LR χ2 = 60.80) but didn't outperform PS (AIC = 2,320.992, C-index = 0.7487, LR χ2 = 114.94). The predictive and discriminative ability of PGS_RS18 was the best (AIC = 2297.434, C-index = 0.7828, LR χ2 = 138.50) when compared with PS and PGS_RS11. CONCLUSION PGS_RS11 was superior to AS but comparable with PS in predicting prognosis. Further validations and refinements are needed for the better incorporation of RS into staging systems. IMPLICATIONS FOR PRACTICE Staging systems are of critical importance in informing prognosis and guiding treatment. This study's objective was to evaluate the newly proposed staging system in the American Joint Committee on Cancer eighth edition staging manual, which combined biological and genomic information with the traditional TNM classification for the first time to determine tumor stages of breast cancer. The superiority of the prognostic and genomic staging system was validated in our cohort and possibly could encourage the utility of genomic assays in clinical practice for staging assessment and prognosis prediction.
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Affiliation(s)
- Shuning Ding
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Jiayi Wu
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Caijin Lin
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Lisa Andriani
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Chihwan Goh
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Weiguo Chen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yafen Li
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Kunwei Shen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Li Zhu
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
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Yu-Qing Y, Lei W, Mei-Ling H, Jing-Jing X, Mei-Chen W, Jiang W, Jun-Sheng H, Rui L, Nan-Lin L. Clinical significance of 21-gene recurrence score assay for hormone receptor-positive, lymph node-negative breast cancer in early stage. Exp Mol Pathol 2019; 108:150-155. [PMID: 31026440 DOI: 10.1016/j.yexmp.2019.04.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 04/12/2019] [Accepted: 04/19/2019] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To identify the relationship between clinical pathological characteristics and the recurrence score (RS) on a 21-gene expression assay in patients with hormone receptor-positive, node-negative breast cancer, as well as the effect of RS on adjuvant decision-making. METHODS The retrospective study was conducted among luminal breast cancer patients admitted to Xijing Hospital between October 10, 2016, and September 14, 2018. Real-time PCR was used for 21-genome detection. Based on the calculated RS, participants were classified into low-risk, moderate-risk, and high-risk groups. Single-factor analysis and multiple logistic regression analysis were performed to explore independent predictors of high RS. Moreover, the effect of RS on adjuvant decision-making was studied. RESULTS Two hundred twenty-two patients with luminal breast cancer, aged 48.3 ± 9.66, were enrolled. Among them, 33.8% had low (13 ± 3.34), 45.5% intermediate (23 ± 3.65), and 20.7% high (37 ± 3.44) RS. According to the single-factor analysis, age, tumor size, Ki-67, molecular subtype, CK5/6 expression, E-cadherin level, and histological grade were positively associated with high RS. Multiple logistic analyses showed that tumor size and histological grade were independent variables that might predict high RS in patients with hormone receptor-positive, node-negative breast cancer. For adjuvant decision-making, the proportion of adjuvant chemotherapy in the intermediate-/high-risk groups was higher than that in the low-risk group, P < 0.001. Compared with the data worldwide, the changes of treatment selection in the present study were similar to those in Japan (23.0% vs. 26%) and America (23.0% vs. 23.0%). Considering the pathology types, 14.3% of patients with invasive breast cancer with lower RS changed treatment recommendations, predominantly from chemo-endocrine to endocrine treatment alone, whereas the percentage in intermediate/high RS groups was 8.1%. CONCLUSIONS Tumor size and histological grade were independent variables, predicting high risk in patients with hormone receptor-positive, node-negative breast cancer; 21-gene RS assessment was potentially a critical tool in guiding adjuvant decision-making in China.
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Affiliation(s)
- Yang Yu-Qing
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China
| | - Wang Lei
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China
| | - Huang Mei-Ling
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China
| | - Xiao Jing-Jing
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China
| | - Wei Mei-Chen
- Department of Pathology, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China
| | - Wu Jiang
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China
| | - Hao Jun-Sheng
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China
| | - Ling Rui
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China.
| | - Li Nan-Lin
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China.
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Macharia LW, Wanjiru CM, Mureithi MW, Pereira CM, Ferrer VP, Moura-Neto V. MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer Aggressiveness. Front Genet 2019; 10:125. [PMID: 30842790 PMCID: PMC6391339 DOI: 10.3389/fgene.2019.00125] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 02/04/2019] [Indexed: 12/14/2022] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that play key regulatory roles in cancer acting as both oncogenes and tumor suppressors. Due to their potential roles in improving cancer prognostic, predictive, diagnostic and therapeutic approaches, they have become an area of intense research focus in recent years. Several studies have demonstrated an altered expression of several miRNAs under hypoxic condition and even shown that the hypoxic microenvironment drives the selection of a more aggressive cancer cell population through cellular adaptations referred as the cancer stem-like cell. These minor fractions of cells are characterized by their self-renewal abilities and their ability to maintain the tumor mass, suggesting their crucial roles in cancer development. This review aims to highlight the interconnected role between miRNAs, hypoxia and the stem-like state in contributing to the cancer aggressiveness as opposed to their independent contributions, and it is based in four aggressive tumors, namely glioblastoma, cervical, prostate, and breast cancers.
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Affiliation(s)
- Lucy Wanjiku Macharia
- Instituto Estadual do Cérebro Paulo Niemeyer - Secretaria de Estado de Saúde, Rio de Janeiro, Brazil.,Programa de Pós-Graduação em Anatomia Patológica, Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Caroline Muriithi Wanjiru
- Instituto Estadual do Cérebro Paulo Niemeyer - Secretaria de Estado de Saúde, Rio de Janeiro, Brazil.,Instituto de Ciências Biomédicas da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Valéria Pereira Ferrer
- Instituto Estadual do Cérebro Paulo Niemeyer - Secretaria de Estado de Saúde, Rio de Janeiro, Brazil.,Programa de Pós-Graduação em Anatomia Patológica, Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vivaldo Moura-Neto
- Instituto Estadual do Cérebro Paulo Niemeyer - Secretaria de Estado de Saúde, Rio de Janeiro, Brazil.,Programa de Pós-Graduação em Anatomia Patológica, Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Kalinowski L, Saunus JM, McCart Reed AE, Lakhani SR. Breast Cancer Heterogeneity in Primary and Metastatic Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1152:75-104. [DOI: 10.1007/978-3-030-20301-6_6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Ibraheem AF, Press DJ, Olopade OI, Huo D. Community clinical practice patterns and mortality in patients with intermediate oncotype DX recurrence scores: Who benefits from chemotherapy? Cancer 2018; 125:213-222. [PMID: 30387876 DOI: 10.1002/cncr.31818] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 08/16/2018] [Accepted: 08/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The Oncotype DX recurrence score (RS) is used as a tool for making decisions about chemotherapy for patients who have hormone receptor (estrogen receptor or progesterone receptor)-positive, HER2-negative breast cancer. There is no benefit from chemotherapy among patients aged ≥50 years who have lymph node-negative disease and an RS from 11 to 25, but the benefit of chemotherapy in the lymph node-positive group remains unknown. METHODS On the basis of data from the National Cancer Data Base between 2010 and 2014, a nationwide, retrospective cohort study included 73,185 women who had stage I through IIIA breast cancer and an RS between 11 and 30. RESULTS Receipt of chemotherapy was associated with a reduced risk of death among patients who had lymph node-positive breast cancer (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.45-0.74; P < .001) after adjusting for other prognostic factors in a multivariable Cox model. The 5-year survival gain ranged from 1.3% (RS 11-17 subgroup), to 3.3% (RS 18-25 subgroup), and to 6.7% (RS 26-30 subgroup). Among patients who had lymph node-negative disease, chemotherapy was associated with a reduced risk of death for those with an RS from 25 to 30 (HR, 0.68; 95% CI, 0.48-0.96; P = .03; 5-year survival gain, 1.8%), but there was no benefit from chemotherapy for patients who had an RS from 11 to 17 (HR, 0.97; 95% CI, 0.61-1.55; P = .90), and there was a marginally significant benefit for women who had an RS from 18 to 25 (HR, 0.79; 95% CI, 0.62-1.00; P = .05). Similar results were observed using propensity score-matching method. CONCLUSIONS The benefit of chemotherapy for patients with breast cancer who have an intermediate RS is driven in a nonlinear fashion by RS: the higher the RS, the larger the absolute benefit. Findings from this study underscore the utility of real-world data to inform joint decision making in practice.
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Affiliation(s)
- Abiola F Ibraheem
- Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - David J Press
- Department of Public Health Sciences, University of Chicago, Chicago, Illinois
| | - Olufunmilayo I Olopade
- Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Dezheng Huo
- Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.,Department of Public Health Sciences, University of Chicago, Chicago, Illinois
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