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Li Y, Ye Y, Tao X, Liang X, Qiu X, Zhao J. Prognostic Features and Predictive Model for Mixed Invasive Ductal and Lobular Breast Carcinoma in Early-Stage Patients. Clin Breast Cancer 2025:S1526-8209(25)00087-4. [PMID: 40263095 DOI: 10.1016/j.clbc.2025.03.019] [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: 01/20/2025] [Revised: 03/17/2025] [Accepted: 03/25/2025] [Indexed: 04/24/2025]
Abstract
INTRODUCTION Mixed invasive ductal and lobular breast carcinoma (IDLC) is a rare and understudied subtype of breast cancer with unique prognostic characteristics. METHODS This study analyzed data from the SEER database and the METABRIC database. Survival outcomes of IDLC were compared with those of IDC and ILC using Kaplan-Meier survival curves and Cox regression analyses. Based on these findings, a prognostic model tailored for IDLC patients was developed using the SEER cohort, which was divided into a training set (70%) and an internal validation set (30%). The model incorporated clinical and molecular features and was externally validated using the METABRIC cohort. Its performance was assessed via C-index, AUC, calibration curves, and decision curve analysis (DCA). RESULTS A total of 26,138 early-stage IDLC patients were included, along with 391,888 IDC and 47,571 ILC patients. In unadjusted analyses, IDLC showed better overall survival (OS) and breast cancer-specific survival (BCSS) compared to both IDC and ILC. However, after multivariate adjustment, the differences in survival outcomes varied. IDLC demonstrated better OS than IDC and better BCSS than ILC. Additionally, a prognostic model for early-stage IDLC that incorporates clinical and molecular features was developed. CONCLUSION This study found that early-stage IDLC had superior BCSS and OS in unadjusted analyses. However, after multivariate adjustment, there was no difference in BCSS between IDLC and IDC, and no difference in OS between IDLC and ILC. A prognostic model was developed and validated, offering precise predictions of OS and BCSS.
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Affiliation(s)
- Yongxin Li
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Yinyin Ye
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Xinlong Tao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Xiao Liang
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Xingchang Qiu
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Jiuda Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China.
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Uçar M, Yılmaz M, Erdiş E, Yücel B. Comparison of Invasive Ductolobular Carcinoma and Lobular Carcinoma: An Observational Study. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:310. [PMID: 40005427 PMCID: PMC11857455 DOI: 10.3390/medicina61020310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/06/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025]
Abstract
Background and Objectives: Mixed ductolobular carcinomas (mDLCs) are tumors that contain both ductal and lobular components. The clinicopathological characteristics and impacts on survival of the two components, which have distinct biological behaviors, are still not clearly understood. This study aimed to compare the clinicopathological characteristics, recurrence/metastasis patterns, and survival outcomes of mDLC and invasive lobular carcinoma (ILC), as well as to investigate the prognostic significance of both histopathologies. Materials and Methods: The outcomes of 132 patients who were followed and treated between 2010 and 2021 were analyzed. Patients were examined in two groups, ILC and mDLC. Chi-square tests were performed to compare the baseline clinicopathological characteristics and treatments. Survival rates were subsequently analyzed using the Kaplan-Meier method and compared using the Cox proportional hazards model. Results: In this study, 80 (61%) patients had ILC histopathology, while 52 (39%) had mDLC histopathology. Differences between the groups were observed in median age (p = 0.038), N stage (p = 0.046), estrogen receptor (ER) status (p = 0.005), lymphovascular invasion (p = 0.007), median tumor diameter (p = 0.050), and frequency of distant metastasis (p = 0.029). The treatments, relapse patterns, and metastasis patterns were similar (p > 0.05). No differences in overall survival (OS) and disease-free survival (DFS) were observed. In the multivariate analysis, mDLC histopathology was identified as a poor prognostic factor (HR: 2.95, CI 95%: 1.10-7.88, p = 0.030). Histopathology (ILC vs. mDCL) was not identified as a prognostic factor in the Cox regression analysis for DFS. Conclusion: Although mDLC has poor clinicopathological features (younger age, more advanced N stage, more ER negativity, more lymphovascular invasion, and more frequency of metastases) and appears more aggressive than ILC, these changes do not affect survival in this study. However, mDLC histopathology seems to be associated with poor prognosis for OS.
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Affiliation(s)
- Mahmut Uçar
- Department of Medical Oncology, Sivas Cumhuriyet University, 58140 Sivas, Turkey;
| | - Mukaddes Yılmaz
- Department of Medical Oncology, Sivas Cumhuriyet University, 58140 Sivas, Turkey;
| | - Eda Erdiş
- Department of Radiation Oncology, Sivas Cumhuriyet University, 58140 Sivas, Turkey; (E.E.); (B.Y.)
| | - Birsen Yücel
- Department of Radiation Oncology, Sivas Cumhuriyet University, 58140 Sivas, Turkey; (E.E.); (B.Y.)
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Melvin Z, Lim D, Jacques A, Falkner NM, Lo G. Is staging breast magnetic resonance imaging for invasive lobular carcinoma worthwhile? ANZ J Surg 2024; 94:1545-1550. [PMID: 38949091 DOI: 10.1111/ans.19140] [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: 02/20/2024] [Revised: 05/24/2024] [Accepted: 06/10/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND Invasive lobular carcinoma (ILC) is challenging to stage accurately using mammography (MG) and ultrasound (US) with undiagnosed ipsilateral and contralateral cancer resulting in poor patient outcomes including return to surgery. Our institution employs routine staging breast MRI in ILC for this reason. However, increased time for further imaging/biopsies contributes to patient anxiety and potentially delays definite management. We aimed to quantify the frequency of staging MRI-detected additional lesions requiring biopsy or follow-up, the added cancer detection rate and MRI prompted change in surgical management. METHODS An observational study on staging breast MRI for newly diagnosed ILC at a tertiary Western Australian hospital from January 2019 to August 2022. Standardized 3T MRI protocol was performed, double read by unblinded fellowship-trained radiologists. Histopathology from biopsy, surgery, or first annual surveillance was the reference standard for additional MRI-detected lesions. RESULTS One hundred ten MRI studies demonstrated 49 (45%) patients had at least one additional clinically significant MRI-detected lesion. Thirty-one patients had an additional ipsilateral lesion detected, of which 18 (58%) proved malignant; 14 (45%) multifocal and 4 (13%) multicentric ILC. Additional work-up of MRI-detected lesions averaged a 9-day delay to definitive surgery compared to patients with a negative or definitively benign MRI. MRI changed surgical planning in 11 of 110 cases from breast conservation surgery (BCS) to mastectomy and there were two contralateral cancers diagnosed. BCS reoperation rate was 11%. CONCLUSION Staging MRI for ILC identifies clinically significant lesions in nearly half of patients, predominantly ipsilateral multifocal disease, without significant delay to definitive surgery.
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Affiliation(s)
- Zebadiah Melvin
- Diagnostic Imaging, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - David Lim
- Surgery, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Angela Jacques
- Institute for Health Research, The University of Notre Dame, Fremantle, Western Australia, Australia
- Department of Research, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Nathalie M Falkner
- Diagnostic Imaging, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Glen Lo
- Diagnostic Imaging, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
- Curtin Medical School, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, Australia
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Shah OS, Nasrazadani A, Foldi J, Atkinson JM, Kleer CG, McAuliffe PF, Johnston TJ, Stallaert W, da Silva EM, Selenica P, Dopeso H, Pareja F, Mandelker D, Weigelt B, Reis-Filho JS, Bhargava R, Lucas PC, Lee AV, Oesterreich S. Spatial molecular profiling of mixed invasive ductal and lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations. Proc Natl Acad Sci U S A 2024; 121:e2322068121. [PMID: 39042692 PMCID: PMC11295029 DOI: 10.1073/pnas.2322068121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 06/13/2024] [Indexed: 07/25/2024] Open
Abstract
Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity - e.g., MDLC with triple-negative breast cancer (TNBC) or basal ductal and estrogen receptor positive (ER+) luminal lobular regions, distinct enrichment of cell cycle arrest/senescence and oncogenic (ER and MYC) signatures, genetic and epigenetic CDH1 inactivation in lobular but not ductal regions, and single-cell ductal and lobular subpopulations with unique oncogenic signatures further highlighting intraregional heterogeneity. Altogether, we demonstrated that the intratumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma.
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MESH Headings
- Humans
- Female
- Carcinoma, Lobular/genetics
- Carcinoma, Lobular/pathology
- Carcinoma, Lobular/metabolism
- Carcinoma, Ductal, Breast/genetics
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Ductal, Breast/metabolism
- Mutation
- Breast Neoplasms/genetics
- Breast Neoplasms/pathology
- Breast Neoplasms/metabolism
- Breast Neoplasms/classification
- Cadherins/genetics
- Cadherins/metabolism
- Gene Expression Regulation, Neoplastic
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Triple Negative Breast Neoplasms/genetics
- Triple Negative Breast Neoplasms/pathology
- Triple Negative Breast Neoplasms/metabolism
- Transcriptome
- Gene Expression Profiling/methods
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Affiliation(s)
- Osama Shiraz Shah
- Womens Cancer Research Center at University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center and Magee Women’s Research Institute, Pittsburgh, PA15213
- Integrative Systems Biology Program, University of Pittsburgh School of Medicine, PittsburghPA15260
| | - Azadeh Nasrazadani
- Womens Cancer Research Center at University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center and Magee Women’s Research Institute, Pittsburgh, PA15213
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA15213
| | - Julia Foldi
- Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA15260
| | - Jennifer M. Atkinson
- Womens Cancer Research Center at University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center and Magee Women’s Research Institute, Pittsburgh, PA15213
- Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA15260
| | - Celina G. Kleer
- Department of Pathology and Rogel Cancer Center, University of Michigan, Ann Arbor, MI48109
| | - Priscilla F. McAuliffe
- Womens Cancer Research Center at University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center and Magee Women’s Research Institute, Pittsburgh, PA15213
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA15232
| | - Tyler J. Johnston
- Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA15213
| | - Wayne Stallaert
- Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA15213
| | - Edaise M. da Silva
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY10065
| | - Pier Selenica
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY10065
| | - Higinio Dopeso
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY10065
| | - Fresia Pareja
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY10065
| | - Diana Mandelker
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY10065
| | - Britta Weigelt
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY10065
| | - Jorge S. Reis-Filho
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY10065
| | - Rohit Bhargava
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA15213
| | - Peter C. Lucas
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, MN55902
| | - Adrian V. Lee
- Womens Cancer Research Center at University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center and Magee Women’s Research Institute, Pittsburgh, PA15213
- Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA15260
| | - Steffi Oesterreich
- Womens Cancer Research Center at University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center and Magee Women’s Research Institute, Pittsburgh, PA15213
- Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA15260
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Shah OS, Nasrazadani A, Foldi J, Atkinson JM, Kleer CG, McAuliffe PF, Johnston TJ, Stallaert W, da Silva EM, Selenica P, Dopeso H, Pareja F, Mandelker D, Weigelt B, Reis-Filho JS, Bhargava R, Lucas PC, Lee AV, Oesterreich S. Spatial molecular profiling of mixed invasive ductal-lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.09.09.557013. [PMID: 38915645 PMCID: PMC11195088 DOI: 10.1101/2023.09.09.557013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially-resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity (e.g., MDLC with TNBC/basal ductal and ER+/luminal lobular regions), distinct enrichment of senescence/dormancy and oncogenic (ER and MYC) signatures, genetic and epigenetic CDH1 inactivation in lobular, but not ductal regions, and single-cell ductal and lobular sub-populations with unique oncogenic signatures further highlighting intra-regional heterogeneity. Altogether, we demonstrated that the intra-tumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma. Significance MDLC displays both ductal and lobular tumor regions. Our multi-omic profiling approach revealed that these morphologically distinct tumor regions harbor distinct intrinsic subtypes and oncogenic features that may cause prognostic uncertainty and therapeutic dilemma. Thus histopathological/molecular profiling of individual tumor regions may guide clinical decision making and benefit patients with MDLC, particularly in the advanced setting where there is increased reliance on next generation sequencing.
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Liu C, Ma G, Xu X, Song S, Yang Z. Can 18F-FES PET Improve the Evaluation of 18F-FDG PET in Patients With Metastatic Invasive Lobular Carcinoma? Clin Nucl Med 2024; 49:301-307. [PMID: 38427956 DOI: 10.1097/rlu.0000000000005085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2024]
Abstract
PURPOSE Invasive lobular carcinoma (ILC) exhibits a low affinity for 18F-FDG. The estrogen receptor (ER) is commonly expressed in ILCs, suggesting a potential benefit of targeting with the ER probe 18F-FES in this patient population. The objective of this study was to evaluate the diagnostic performance of 18F-FES imaging in patients with metastatic ILC and compare it with that of 18F-FDG. METHODS We conducted a retrospective analysis of 20 ILC patients who underwent concurrent 18F-FES and 18F-FDG PET/CT examinations in our center. 18F-FES and 18F-FDG imaging were analyzed to determine the total count of tracer-avid lesions in nonbone sites and their corresponding organ systems, assess the extent of anatomical regions involved in bone metastases, and measure the SUVmax values for both tracers. RESULTS Among 20 ILC patients, 65 nonbone lesions were found to be distributed in 13 patients, and 16 patients were diagnosed with bone metastasis, which was distributed in 54 skeletal anatomical regions. The detection rate of 18F-FDG in nonbone lesions was higher than that of 18F-FES (57 vs 37, P < 0.001). 18F-FES demonstrated a superior ability to detect nonbone lesions in 4 patients, whereas 18F-FDG was superior in 5 patients (P > 0.05). Among 9/16 patients with bone metastasis, 18F-FES demonstrated a significant advantage in the detection of bone lesions compared with 18F-FDG (P = 0.05). Furthermore, patients with only 18F-FES-positive lesions (12/12) were administered endocrine regimens, whereas patients lacking 18F-FES uptake (2/3) predominantly received chemotherapy. CONCLUSIONS 18F-FES is more effective than 18F-FDG in detecting bone metastasis in ILC, but it does not demonstrate a significant advantage in nonbone lesions. Additionally, the results of examination with 18F-FES have the potential to guide patient treatment plans.
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Lohani KR, Hoskin TL, Day CN, Yasir S, Boughey JC, Degnim AC. Lobular-Like Features and Outcomes of Mixed Invasive Ductolobular Breast Cancer (MIDLC): Insights from 54,403 Stage I-III MIDLC Patients. Ann Surg Oncol 2024; 31:936-946. [PMID: 37872454 DOI: 10.1245/s10434-023-14455-7] [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: 07/03/2023] [Accepted: 10/03/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized. METHOD The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis. RESULTS We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p < 0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p < 0.001) and ILC (hazard ratio 0.91, p < 0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC). CONCLUSIONS MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery.
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Affiliation(s)
- Kush R Lohani
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Tanya L Hoskin
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Courtney N Day
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Saba Yasir
- Department of Pathology, Mayo Clinic, Rochester, MN, USA
| | - Judy C Boughey
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Amy C Degnim
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
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Göker M, Denys H, Hendrix A, De Wever O, Van de Vijver K, Braems G. Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer. Breast Cancer Res 2023; 25:146. [PMID: 37993928 PMCID: PMC10664297 DOI: 10.1186/s13058-023-01745-x] [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: 06/20/2022] [Accepted: 11/12/2023] [Indexed: 11/24/2023] Open
Abstract
PURPOSE The aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC). METHODS Data of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001-2015, were analyzed. RESULTS ILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan-Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08-2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78-0.91), LVSI (hazard ratio 1.75, 95% CI 1.12-2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03-5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02-1.07), LVSI (hazard ratio 3.62, 95% CI 1.92-6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73-0.89). CONCLUSION The histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.
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Affiliation(s)
- Menekse Göker
- Department of Gynaecology, Ghent University Hospital, Ghent, Belgium.
| | - Hannelore Denys
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
| | - An Hendrix
- Laboratory for Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium
| | - Olivier De Wever
- Laboratory for Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium
| | | | - Geert Braems
- Department of Gynaecology, Ghent University Hospital, Ghent, Belgium
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Danzinger S, Pöckl K, Kronawetter G, Pfeifer C, Behrendt S, Gscheidlinger P, Harrasser L, Mühlböck H, Dirschlmayer W, Schauer C, Reitsamer R, Uher H, Schönau K, Delmarko I, Singer CF. Axillary lymph node status and invasive lobular breast cancer : Analysis of the Clinical Tumor Register of the AGO Austria. Wien Klin Wochenschr 2023; 135:463-471. [PMID: 37010596 PMCID: PMC10497662 DOI: 10.1007/s00508-023-02162-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 02/10/2023] [Indexed: 04/04/2023]
Abstract
BACKGROUND Invasive lobular carcinoma (ILC) represents the second most common type of invasive breast cancer (BC). Although ILC generally have good prognostic properties (positive estrogen receptor, ER, low tumor grade), they are generally diagnosed at a more advanced stage. The data on the axillary lymph node status in ILC compared to invasive ductal carcinoma (IDC) are considered controversial. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register. METHODS Data of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO) were retrospectively analyzed. Patients with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were included. A total of 2127 tumors were evaluated and compared in 2 groups, ILC n = 303, IDC n = 1824. RESULTS A total of 2095 patients were analyzed in the study. In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (odds ratio, OR 1.93; 95% confidence interval, CI 1.19-3.14; p = 0.008 and OR 3.22; 95% CI: 1.47-7.03; p = 0.003; respectively). Other factors associated with ILC were tumor grades 2 and 3, positive ER, and pathological tumor stage (pT) 2 and pT3. In contrast, concomitant ductal carcinoma in situ, overexpression of the human epidermal growth factor receptor 2 (HER2), and a moderate and high proliferation rate (Ki67) were found less frequently in ILC. CONCLUSION The data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.
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Affiliation(s)
- Sabine Danzinger
- Department of Obstetrics and Gynecology, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria
| | - Karin Pöckl
- Department of Obstetrics and Gynecology, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria
| | - Gerit Kronawetter
- Department of Obstetrics and Gynecology, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria
| | - Christian Pfeifer
- Department of Statistics, University of Innsbruck, Innsbruck, Austria
| | - Sandra Behrendt
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Patricia Gscheidlinger
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Lois Harrasser
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Helmut Mühlböck
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Walter Dirschlmayer
- Department of Obstetrics and Gynecology, Hospital Barmherzige Schwestern Ried, Ried im Innkreis, Austria
| | - Christian Schauer
- Department of Gynecology, Hospital Barmherzige Brüder Graz, Graz, Austria
| | - Roland Reitsamer
- Department of Gynecology, Paracelsus Medical University, University Hospital Salzburg, Landeskrankenhaus Salzburg, Salzburg, Austria
| | - Heidemarie Uher
- Department of Surgery, Breast Health Center, Hospital Landstraße, Vienna, Austria
| | - Kristina Schönau
- Department of General, Visceral and Tumor Surgery, Breast Health Center, Hospital Ottakring, Vienna, Austria
| | - Irmgard Delmarko
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Christian F. Singer
- Department of Obstetrics and Gynecology, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria
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Yu J, da Silva EM, La HS, Clark BZ, Fine JL, Carter GJ, Villatoro TM, Soong TR, Lee AV, Oesterreich S, Basili T, Blanco-Heredia J, Selenica P, Ye Q, Da Cruz Paula A, Dopeso H, Gazzo A, Marra A, Pareja F, Reis-Filho JS, Bhargava R. Clinicopathologic and genomic features of lobular like invasive mammary carcinoma: is it a distinct entity? NPJ Breast Cancer 2023; 9:60. [PMID: 37443169 DOI: 10.1038/s41523-023-00566-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
This study describes "lobular-like invasive mammary carcinomas" (LLIMCas), a group of low- to intermediate-grade invasive mammary carcinomas with discohesive, diffusely infiltrative cells showing retained circumferential membranous immunoreactivity for both E-cadherin and p120. We analyzed the clinical-pathologic features of 166 LLIMCas compared to 104 classical invasive lobular carcinomas (ILCs) and 100 grade 1 and 2 invasive ductal carcinomas (IDCs). Tumor size and pT stage of LLIMCas were intermediate between IDCs and ILCs, and yet often underestimated on imaging and showed frequent positive margins on the first resection. Despite histomorphologic similarities to classical ILC, the discohesion in LLIMCa was independent of E-cadherin/p120 immunophenotypic alteration. An exploratory, hypothesis-generating analysis of the genomic features of 14 randomly selected LLIMCas and classical ILCs (7 from each category) was performed utilizing an FDA-authorized targeted capture sequencing assay (MSK-IMPACT). None of the seven LLIMCas harbored CDH1 loss-of-function mutations, and none of the CDH1 alterations detected in two of the LLIMCas was pathogenic. In contrast, all seven ILCs harbored CDH1 loss-of-function mutations coupled with the loss of heterozygosity of the CDH1 wild-type allele. Four of the six evaluable LLIMCas were positive for CDH1 promoter methylation, which may partially explain the single-cell infiltrative morphology seen in LLIMCa. Further studies are warranted to better define the molecular basis of the discohesive cellular morphology in LLIMCa. Until more data becomes available, identifying LLIMCas and distinguishing them from typical IDCs and ILCs would be justified. In patients with LLIMCas, preoperative MRI should be entertained to guide surgical management.
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Affiliation(s)
- Jing Yu
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA.
| | - Edaise M da Silva
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hae-Sun La
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Beth Z Clark
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Jeffrey L Fine
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Gloria J Carter
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Tatiana M Villatoro
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA
| | - T Rinda Soong
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Adrian V Lee
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA, USA
| | - Steffi Oesterreich
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA, USA
| | - Thais Basili
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Juan Blanco-Heredia
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Pier Selenica
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Qiqi Ye
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Arnaud Da Cruz Paula
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Higinio Dopeso
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Gazzo
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Antonio Marra
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Fresia Pareja
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jorge S Reis-Filho
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Rohit Bhargava
- Department of Pathology, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA.
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11
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Kuba MG, Brogi E. Update on lobular lesions of the breast. Histopathology 2023; 82:36-52. [PMID: 36482279 PMCID: PMC9752180 DOI: 10.1111/his.14829] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/09/2022] [Accepted: 10/12/2022] [Indexed: 12/13/2022]
Abstract
The current histological classification of in-situ and invasive lobular carcinomas (ILCs) includes different morphological variants, some of which have been recently described. In this review, we will focus upon: (i) the diagnostic criteria of non-invasive lobular neoplasia and treatment implications across different countries; (ii) utility and limitations of immunohistochemistry; (iii) recently described variants of ILC; and (iv) the significance of lobular differentiation in invasive carcinoma for clinical management.
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Affiliation(s)
- Maria Gabriela Kuba
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Edi Brogi
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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12
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Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies. NPJ Breast Cancer 2022; 8:131. [PMID: 36539444 PMCID: PMC9768132 DOI: 10.1038/s41523-022-00499-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022] Open
Abstract
The addition of targeted therapies (TT) to endocrine therapy (ET) has improved the outcomes of patients with HR-positive, HER2-negative metastatic breast cancer (mBC). However, it is unknown whether patients with invasive lobular carcinoma (ILC) or mixed invasive ductal and lobular carcinoma (mixed) histologies experience the same magnitude of benefit from this therapy as those with invasive ductal carcinoma (IDC). We aim to determine whether patients with IDC, ILC, and mixed HR+/HER2- mBC derive similar benefit from the addition of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is), mammalian target of rapamycin inhibitor (mTORi), and phosphoinositide 3-kinase inhibitor (PI3Ki) to ET in HR+/HER2- mBC. We conducted an observational, population-based investigation using data from the MD Anderson prospectively collected database. We conducted a histology-based analysis of progression-free survival (PFS) and overall survival (OS) durations in 3784 patients with HR+/HER2- mBC who were treated with TT plus ET between January 1, 2010, and December 31, 2021. Out of the 3784 patients, 2975 were included in the final analysis. Of these, 2249 received CDK4/6is (81% IDC, 15% ILC, and 4% mixed), 1027 received everolimus (82% IDC, 14% ILC, and 4% mixed) and 49 received alpelisib (81% IDC and 19% ILC). The addition of targeted therapy to ET did not result in statistically significant differences in PFS or OS duration among patients with IDC, ILC, and mixed HR+/HER2- mBC. We concluded that for patients with HR+/HER2- mBC, the addition of TT to ET leads to a similar magnitude of benefit, irrespective of histology.
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13
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Davey MG, Keelan S, Lowery AJ, Kerin MJ. The Impact of Chemotherapy Prescription on Long-Term Survival Outcomes in Early-Stage Invasive Lobular Carcinoma - A Systematic Review and Meta-Analysis. Clin Breast Cancer 2022; 22:e843-e849. [PMID: 36229335 DOI: 10.1016/j.clbc.2022.09.005] [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: 06/04/2022] [Revised: 09/06/2022] [Accepted: 09/14/2022] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Invasive lobular carcinoma (ILCs) are typically endocrine responsive breast cancers which respond poorly to chemotherapy. The long-term survival advantage of prescribing chemotherapy in such cases remains unclear. To perform a systematic review and meta-analysis assessing, the impact of prescribing chemotherapy in such patients on long-term disease-free (DFS) and overall (OS) survival outcomes. METHODS A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. Ten-year DFS and OS were pooled as odds ratios (ORs) with 95% confidence intervals (CI) using the Mantel-Haenszel method. Time-to-effect modelling was performed using the generic inverse variance method. RESULTS Overall, 9 studies including 28,218 patients were included. The mean follow-up was 74 months (range: 0-150 months) and mean age was 60 years (range: 22-90 years). Of these, 34.7% received chemotherapy (9,797/28,218) and 66.3% did not receive chemotherapy (18,421/28,218). Chemotherapy prescription failed to improve 10-year DFS (OR: 0.89, 95% CI: 0.65-1.23) and OS (OR: 0.92, 95% CI: 0.72-1.18). When using time-to-effect modelling, chemotherapy prescription failed to improve DFS (hazard ratio (HR): 1.01, 95% CI: 0.78-1.31) and OS (HR: 1.07, 95% CI: 0.89-1.27, I2= 67%). CONCLUSION This meta-analysis illustrates no long-term survival advantage associated with chemotherapy prescription in the setting of early-stage ILC. In the absence of well-designed, prospective clinical trials evaluating the impact of chemotherapy on long-term outcomes in ILC, these results should be considered by the multidisciplinary team when deciding on the value of systemic chemotherapy prescription in ILC.
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Affiliation(s)
- Matthew G Davey
- Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Republic of Ireland.
| | - Stephen Keelan
- Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Republic of Ireland
| | - Aoife J Lowery
- Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Republic of Ireland
| | - Michael J Kerin
- Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Republic of Ireland
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14
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Sadeghipour N, Tseng J, Anderson K, Ayalasomayajula S, Kozlov A, Ikeda D, DeMartini W, Hori SS. Tumor volume doubling time estimated from digital breast tomosynthesis mammograms distinguishes invasive breast cancers from benign lesions. Eur Radiol 2022; 33:429-439. [PMID: 35779088 DOI: 10.1007/s00330-022-08966-2] [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: 10/28/2021] [Revised: 06/09/2022] [Accepted: 06/13/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVES The aim of this study was to determine whether lesion size metrics on consecutive screening mammograms could predict malignant invasive carcinoma versus benign lesion outcome. METHODS We retrospectively reviewed suspicious screen-detected lesions confirmed by biopsy to be invasive breast cancers or benign that were visible on current and in-retrospect prior screening mammograms performed with digital breast tomosynthesis from 2017 to 2020. Four experienced radiologists recorded mammogram dates, breast density, lesion type, lesion diameter, and morphology on current and prior exams. We used logistic regression models to evaluate the association of invasive breast cancer outcome with lesion size metrics such as maximum dimension, average dimension, volume, and tumor volume doubling time (TVDT). RESULTS Twenty-eight patients with invasive ductal carcinoma or invasive lobular carcinoma and 40 patients with benign lesions were identified. The mean TVDT was significantly shorter for invasive breast cancers compared to benign lesions (0.84 vs. 2.5 years; p = 0.0025). Patients with a TVDT of less than 1 year were shown to have an odds ratio of invasive cancer of 6.33 (95% confidence interval, 2.18-18.43). Logistic regression adjusted for age, lesion maximum dimension, and lesion volume demonstrated that shorter TVDT was the size variable significantly associated with invasive cancer outcome. CONCLUSION Invasive breast cancers detected on current and in-retrospect prior screening mammograms are associated with shorter TVDT compared to benign lesions. If confirmed to be sufficiently predictive of benignity in larger studies, lesions visible on mammograms which in comparison to prior exams have longer TVDTs could potentially avoid additional imaging and/or biopsy. KEY POINTS • We propose tumor volume doubling time as a measure to distinguish benign from invasive breast cancer lesions. • Logistic regression results summarized the utility of the odds ratio in retrospective clinical mammography data.
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Affiliation(s)
- Negar Sadeghipour
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.,The Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA.,Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, USA
| | - Joseph Tseng
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
| | - Kristen Anderson
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.,The Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Shivani Ayalasomayajula
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.,The Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Andrew Kozlov
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.,The University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Debra Ikeda
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
| | - Wendy DeMartini
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
| | - Sharon S Hori
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA. .,The Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA. .,Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, USA.
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15
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Kang B, Lee J, Park JY, Jeong JY. Efficacy of breast magnetic resonance for surgical decision with reflecting pathologic findings in mixed invasive ductal and lobular breast carcinoma. Asian J Surg 2022; 45:1326-1328. [DOI: 10.1016/j.asjsur.2022.01.072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/26/2022] [Indexed: 11/29/2022] Open
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16
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Mouabbi JA, Hassan A, Lim B, Hortobagyi GN, Tripathy D, Layman RM. Invasive lobular carcinoma: an understudied emergent subtype of breast cancer. Breast Cancer Res Treat 2022; 193:253-264. [DOI: 10.1007/s10549-022-06572-w] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/07/2022] [Indexed: 12/22/2022]
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17
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Dalenc F, Lusque A, De La Motte Rouge T, Pistilli B, Brain E, Pasquier D, Debled M, Thery JC, Gonçalves A, Desmoulins I, Levy C, Uwer L, Ferrero JM, Eymard JC, Mouret-Reynier MA, Patsouris A, Frenel JS, Petit T, Chevrot M, Bachelot T, Guiu S. Impact of lobular versus ductal histology on overall survival in metastatic breast cancer: a French retrospective multicentre cohort study. Eur J Cancer 2022; 164:70-79. [PMID: 35176614 DOI: 10.1016/j.ejca.2021.12.031] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/22/2021] [Accepted: 12/27/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND The impact of the histological lobular subtype on overall survival (OS) in metastatic breast cancer (MBC) is still under debate, with very few data available. PATIENTS AND METHODS Using the French national multicentre Epidemiological Strategy and Medico Economics [ESME]) data platform, the primary objective was to compare the OS of patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) MBC, with adjustment on the main prognostic factors using two approaches: multivariable analysis and matching with a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1) and describe patients and tumour characteristics. RESULTS Of the 16,703 patients with MBC in the ESME database, 13,111 met all inclusion criteria for the present analysis. One-thousand eight-hundred and four (13.8%) patients had ILC and 11.307 (86.2%) IDC. In the multivariable analysis, patients with ILC had a worse OS [hazard ratio (HR): 1.31; 95%CI 1.20-1.42; p < 0.0001] and a worse PFS1 (HR: 1.15; 95%CI 1.07-1.22; p < 0.0001) as compared with those with IDC, independently of hormone receptor and HER2 status. Interestingly, OS was better (HR 0.79; 95% confidence interval [CI] 0.64-0.98; p = 0.0302), worse (HR: 1.17; 95%CI 1.08-1.27; p = 0.0001) or similar (HR: 0.88; 95%CI 0.67-1.15; p = 0.3455) in patients with ILC with triple-negative, hormone receptor-positive/HER2-negative and HER2-positive MBC, respectively, compared with patients with IDC. CONCLUSION Lobular histology is an independent adverse prognostic factor among women with MBC. ILC MBC could be considered a specific entity. Dedicated prospective studies are needed to tailor the management of these patients.
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Affiliation(s)
- Florence Dalenc
- Department of Medical Oncology, Institut Claudius Regaud-IUCT Oncopole, Toulouse, France
| | - Amélie Lusque
- Department of Biostatistics, Institut Claudius Regaud-IUCT Oncopole, Toulouse, France
| | | | - Barbara Pistilli
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France
| | - Etienne Brain
- Department of Medical Oncology, Saint-Cloud and Paris, France
| | - David Pasquier
- Department of Radiation Oncology, Centre Oscar Lambret, Lille, France
| | - Marc Debled
- Department of Medical Oncology, Institut Bergonie, Bordeaux, France
| | | | - Anthony Gonçalves
- Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France
| | - Isabelle Desmoulins
- Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France
| | - Christelle Levy
- Department of Medical Oncology, Centre François Baclesse, Caen, France
| | - Lionel Uwer
- Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France
| | - Jean-Marc Ferrero
- Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France
| | | | | | - Anne Patsouris
- Department of MedicalOncology, Institut de Cancérologie de L'Ouest-Paul Papin, Angers, France
| | - Jean-Sébastien Frenel
- Department of MedicalOncology, Institut de Cancérologie de L'Ouest-René Gauducheau, Nantes, France
| | - Thierry Petit
- Department of Medical Oncology, Centre Paul Strauss, Strasbourg, France
| | - Michael Chevrot
- Department of Real Worl Data, Data Unit, Unicancer, Paris, France
| | - Thomas Bachelot
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France
| | - Séverine Guiu
- Department of Medical Oncology, Institut Du Cancer de Montpellier, Montpellier, France.
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18
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Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up. Breast 2021; 59:294-300. [PMID: 34388695 PMCID: PMC8361199 DOI: 10.1016/j.breast.2021.07.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/08/2021] [Accepted: 07/16/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. PURPOSE To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. MATERIAL AND METHODS From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. RESULTS ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. CONCLUSIONS During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small.
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Danzinger S, Hielscher N, Izsó M, Metzler J, Trinkl C, Pfeifer C, Tendl-Schulz K, Singer CF. Invasive lobular carcinoma: clinicopathological features and subtypes. J Int Med Res 2021; 49:3000605211017039. [PMID: 34187216 PMCID: PMC8258769 DOI: 10.1177/03000605211017039] [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] [Indexed: 11/16/2022] Open
Abstract
Objective To analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors. Methods We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC). Results Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (+), have a lower proliferation rate (Ki67 <14%), and a higher pathological T stage (pT2–4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ER+, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1–3) was significantly more frequent with ILC versus IDC. Conclusions Our data suggest that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.
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Affiliation(s)
- Sabine Danzinger
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
| | - Nora Hielscher
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
| | - Miriam Izsó
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
| | - Johanna Metzler
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
| | - Carmen Trinkl
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
| | - Christian Pfeifer
- Department of Statistics, University of Innsbruck, Innsbruck, Austria
| | | | - Christian F Singer
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
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20
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Ji L, Cheng L, Zhu X, Gao Y, Fan L, Wang Z. Risk and prognostic factors of breast cancer with liver metastases. BMC Cancer 2021; 21:238. [PMID: 33676449 PMCID: PMC7937288 DOI: 10.1186/s12885-021-07968-5] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 02/24/2021] [Indexed: 01/10/2023] Open
Abstract
Background Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM). Methods Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients. Results Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88–3.66; P < 0.001) and HR−/HER2+ (HR = 3.43; 95% CI = 2.28–5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58–0.95; P < 0.001). Conclusions Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-07968-5.
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Affiliation(s)
- Lei Ji
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lei Cheng
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiuzhi Zhu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yu Gao
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lei Fan
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. .,Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
| | - Zhonghua Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. .,Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
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Miklikova S, Trnkova L, Plava J, Bohac M, Kuniakova M, Cihova M. The Role of BRCA1/2-Mutated Tumor Microenvironment in Breast Cancer. Cancers (Basel) 2021; 13:575. [PMID: 33540843 PMCID: PMC7867315 DOI: 10.3390/cancers13030575] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/23/2021] [Accepted: 01/29/2021] [Indexed: 12/15/2022] Open
Abstract
Taking into account the factors of high incidence rate, prevalence and mortality, breast cancer represents a crucial social and economic burden. Most cases of breast cancer develop as a consequence of somatic mutations accumulating in mammary epithelial cells throughout lifetime and approximately 5-10% can be ascribed to monogenic predispositions. Even though the role of genetic predispositions in breast cancer is well described in the context of genetics, very little is known about the role of the microenvironment carrying the same aberrant cells impaired by the germline mutation in the breast cancer development and progression. Based on the clinical observations, carcinomas carrying mutations in hereditary tumor-suppressor genes involved in maintaining genome integrity such as BRCA1/2 have worse prognosis and aggressive behavior. One of the mechanisms clarifying the aggressive nature of BRCA-associated tumors implies alterations within the surrounding adipose tissue itself. The objective of this review is to look at the role of BRCA1/2 mutations in the context of breast tumor microenvironment and plausible mechanisms by which it contributes to the aggressive behavior of the tumor cells.
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Affiliation(s)
- Svetlana Miklikova
- Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (S.M.); (L.T.); (J.P.)
| | - Lenka Trnkova
- Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (S.M.); (L.T.); (J.P.)
| | - Jana Plava
- Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (S.M.); (L.T.); (J.P.)
| | - Martin Bohac
- 2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Klenova 1, 83310 Bratislava, Slovakia;
- Department of Oncosurgery, National Cancer Institute, Klenova 1, 83310 Bratislava, Slovakia
- Regenmed Ltd., Medena 29, 81108 Bratislava, Slovakia
| | - Marcela Kuniakova
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia;
| | - Marina Cihova
- Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (S.M.); (L.T.); (J.P.)
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Karatas M, Zengel B, Durusoy R, Tasli F, Adibelli Z, Simsek C, Uslu A. Clinicopathologic features of single bone metastasis in breast cancer. Medicine (Baltimore) 2021; 100:e24164. [PMID: 33429799 PMCID: PMC7793343 DOI: 10.1097/md.0000000000024164] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 12/09/2020] [Indexed: 01/05/2023] Open
Abstract
The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.
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Affiliation(s)
- Murat Karatas
- Department of General Surgery, The University of Health Sciences, Izmir Bozyaka Education and Training Hospital
| | - Baha Zengel
- Department of General Surgery, The University of Health Sciences, Izmir Bozyaka Education and Training Hospital
| | - Raika Durusoy
- Department of Public Health, Ege University, Medical Faculty
| | | | - Zehra Adibelli
- Department of Radiology, The University of Health Sciences, Izmir Bozyaka Education and Training Hospital
| | - Cenk Simsek
- Department of General Surgery, The University of Health Sciences, Izmir Bozyaka Education and Training Hospital
| | - Adam Uslu
- Department of General Surgery, The University of Health Sciences, Izmir Bozyaka Education and Training Hospital
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McCart Reed AE, Kalinowski L, Simpson PT, Lakhani SR. Invasive lobular carcinoma of the breast: the increasing importance of this special subtype. Breast Cancer Res 2021; 23:6. [PMID: 33413533 PMCID: PMC7792208 DOI: 10.1186/s13058-020-01384-6] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/15/2020] [Indexed: 12/15/2022] Open
Abstract
Invasive lobular carcinoma (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast cancer cases. ILCs are noted for their lack of E-cadherin function, which underpins their characteristic discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, tumours are luminal in molecular subtype, being oestrogen and progesterone receptor positive, and HER2 negative. Since last reviewing the lobular literature (McCart Reed et al., Breast Cancer Res 17:12, 2015), there has been a considerable increase in research output focused on this tumour type, including studies into the pathology and management of disease, a high-resolution definition of the genomic landscape of tumours as well as the evolution of several potential therapeutic avenues. There abounds a huge amount of new data, which we will review herein.
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Affiliation(s)
- Amy E McCart Reed
- UQ Centre for Clinical Research, The University of Queensland, Herston, Brisbane, Australia.
- QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
| | - Lauren Kalinowski
- UQ Centre for Clinical Research, The University of Queensland, Herston, Brisbane, Australia
- Department of Histopathology, Sullivan Nicolaides Pathology, Bowen Hills, Brisbane, Australia
| | - Peter T Simpson
- UQ Centre for Clinical Research, The University of Queensland, Herston, Brisbane, Australia
- QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia
| | - Sunil R Lakhani
- UQ Centre for Clinical Research, The University of Queensland, Herston, Brisbane, Australia
- Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, Brisbane, Australia
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24
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The prognosis of invasive ductal carcinoma, lobular carcinoma and mixed ductal and lobular carcinoma according to molecular subtypes of the breast. Breast Cancer 2020; 28:187-195. [PMID: 32812198 DOI: 10.1007/s12282-020-01146-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 08/12/2020] [Indexed: 01/20/2023]
Abstract
BACKGROUND To investigate the prognosis of females with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) according to hormone receptor (HR) and HER2 status. METHODS Data of 171,881 patients from the SEER database were analyzed. Propensity score matching was used to balance the covariates. Breast cancer-specific survival (BCSS) and overall survival (OS) of IDC, ILC, and IDLC were investigated. RESULTS Patients with ILC were older, had lower tumor grade, higher tumor stage, larger tumor size, more nodal metastasis, higher estrogen receptor(+), lower HER2(-), and less likely to receive partial mastectomy and chemotherapy compared with IDC and IDLC. ILC and IDLC showed better prognosis than IDC after matching by Kaplan-Meier curves. Multivariate Cox regression showed better OS of ILC and IDLC compared with IDC with hazard ratio and a 95% confidence interval of 0.84 (0.77-0.90) and 0.91 (0.83-1.00), respectively. For HR(+)HER2(-) subgroup, ILC showed better OS than IDC; IDC showed worse BCSS and OS than IDLC. For HR(+)HER2(+); ILC showed better OS compared with IDLC; there were no survival differences of IDC, ILC, and IDLC for HER2(+). For HR(-)HER2(-), ILC and IDC showed better BCSS and OS compared with IDLC by multivariate analysis. CONCLUSIONS The prognoses of female patients with IDC, ILC or IDLC were associated with the molecular subtypes of breast carcinoma. Management decisions should be based on pathological types and molecular subtypes.
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Duraker N, Hot S, Akan A, Nayır PÖ. A Comparison of the Clinicopathological Features, Metastasis Sites and Survival Outcomes of Invasive Lobular, Invasive Ductal and Mixed Invasive Ductal and Lobular Breast Carcinoma. Eur J Breast Health 2020; 16:22-31. [PMID: 31912010 DOI: 10.5152/ejbh.2019.5004] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 10/25/2019] [Indexed: 11/22/2022]
Abstract
Objective We compared the breast cancer patients with invasive lobular carcinoma (ILC), invasive ductal carcinoma (IDC) and mixed invasive ductal and lobular carcinoma (IDLC) in terms of clinicopathological and treatment features, metastatic patterns and long-term survival. Materials and Methods In a 10 years patient cohort, 3412 patients with unilateral breast carcinoma were enrolled in the study. Tumors were classified histologically according to criteria described by World Health Organization classification. Results The highest rate of T3 tumors were found in IDLC patients, the lowest in IDC patients, and the difference between groups was significant only in comparison of IDC vs IDLC. Axillary positivity rate was highest in IDLC, lowest in ILC; differences were significant in comparisons of IDLC vs ILC and IDLC vs IDC. There was no significant difference between the patient groups in terms of surgical treatment, mastectomy and breast conserving surgery. Rate of bone metastasis was highest in IDLC, lowest in IDC, with significant difference between IDLC and IDC. Locoregional recurrence-free survival (LRFS) rate was 90.9% in ILC patients, 92.5% in IDC patients, 92.9% in IDLC patients, with no significant difference between the groups; in multivariate Cox analysis, histological type had no prognostic significance (p=0.599). Distant metastasis-free survival (DMFS) rate was 66.2% in ILC patients, 66.7% in IDC patients, 57.1% in IDLC patients; in multivariate Cox analysis, histological type had no prognostic significance (p=0.392). Conclusion Although these results suggest that IDLC may have a worse prognosis than IDC and ILC, in multivariate analysis LRFS and DMFS were not significantly different among the histological type groups.
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Affiliation(s)
- Nüvit Duraker
- Department of General Surgery, University of Health Sciences, Okmeydanı Training and Research Hospital, İstanbul, Turkey
| | - Semih Hot
- Department of General Surgery, University of Health Sciences, Okmeydanı Training and Research Hospital, İstanbul, Turkey
| | - Arzu Akan
- Department of General Surgery, University of Health Sciences, Okmeydanı Training and Research Hospital, İstanbul, Turkey
| | - Pınar Özay Nayır
- Department of Pathology, University of Health Sciences, Okmeydanı Training and Research Hospital, İstanbul, Turkey
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Lehrer S, Green S, Dembitzer FR, Rheinstein PH, Rosenzweig KE. Increased RNA Expression of von Willebrand Factor Gene Is Associated With Infiltrating Lobular Breast Cancer and Normal PAM50 Subtype. Cancer Genomics Proteomics 2019; 16:147-153. [PMID: 31018945 DOI: 10.21873/cgp.20120] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 02/27/2019] [Accepted: 03/12/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Infiltrating lobular carcinoma (ILC) is the second most common histologicaI subtype of breast cancer, accounting for 10% of all cases. ILC has a characteristic genomic profile. ILC shows a high frequency of cadherin 1 (CDH1) mutations, along with loss of phosphatase and tensin homolog (PTEN), activation of alpha serine/threonine kinase (AKT), and mutations in T-box transcription factor (TBX3) and forkhead box protein A1 (FOXA1). We suspected that another gene, von Willebrand factor (VWF), might also be part of the profile, since coagulation tests reveal significant differences in patients with breast cancer. MATERIALS AND METHODS For newly-diagnosed breast cancer, the association between VWF and histology in the GDC Breast Cancer dataset in The Cancer Genome Atlas (TCGA) was evaluated. The following were used to access and analyze the data: Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov/); Xena browser (https://xenabrowser.net); cBioportal (http://cbioportal.org); Oncomine (https://oncomine.org); and Prediction Analysis of Microarray 50 (PAM50). RESULTS Patients with ILC had higher VWF RNA expression than patients with infiltrating ductal carcinoma and other histology. The difference of expression was present to the same degree in both pre-menopausal and post-menopausal patients. Nine alterations in VWF and PTEN were significantly co-occurrent. Considering all histologies in 843 samples, Tukey's honest significant difference post hoc test showed that VWF RNA expression of the normal subtype was significantly greater than that of the other subtypes (p<0.001). CONCLUSION Our finding of significantly higher VWF RNA expression in the PAM50 normal (non-basal-like) breast cancer subtype suggests that VWF protein measurement might complement or corroborate PAM50 results. VWF and PAM50 results both suggesting a low risk of recurrence might make the decision whether to give chemotherapy easier, especially if VWF protein were an independent predictor.
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Affiliation(s)
- Steven Lehrer
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A
| | - Sheryl Green
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A
| | - Francine R Dembitzer
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A
| | | | - Kenneth E Rosenzweig
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A
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Flores-Díaz D, Arce C, Flores-Luna L, Reynoso-Noveron N, Lara-Medina F, Matus JA, Bargallo-Rocha E, Pérez V, Villarreal-Garza C, Cabrera-Galeana P, Mohar A. Impact of invasive lobular carcinoma on long-term outcomes in Mexican breast cancer patients. Breast Cancer Res Treat 2019; 176:243-249. [PMID: 30997623 DOI: 10.1007/s10549-019-05234-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 04/10/2019] [Indexed: 10/27/2022]
Abstract
PURPOSE The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC). METHODS We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis. RESULTS Median follow-up time was 42.13 months (IQ25 25.2-IQ75 72.06). The median age was 50.9 years (IQ25 43.5-IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36-5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08-1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28-2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09-2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15-6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69-3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27-2.92; p = 0.02). CONCLUSION Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.
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Affiliation(s)
- Diana Flores-Díaz
- Breast Medical Oncology, National Institute of Cancer (INCan), Mexico City, Mexico
| | - Claudia Arce
- Breast Medical Oncology, National Institute of Cancer (INCan), Mexico City, Mexico
| | - Lourdes Flores-Luna
- Research Center in Health Population, National Institute of Public Health, Cuernavaca, Morelos, Mexico
| | | | - Fernando Lara-Medina
- Breast Medical Oncology, National Institute of Cancer (INCan), Mexico City, Mexico
| | - Juan Antonio Matus
- Breast Medical Oncology, National Institute of Cancer (INCan), Mexico City, Mexico
| | | | - Víctor Pérez
- Breast Pathology Department, National Institute of Cancer (INCan), Mexico City, Mexico
| | | | | | - Alejandro Mohar
- Breast Epidemiology Unit, National Institute of Cancer (INCan), Mexico City, Mexico.
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Haque W, Teh BS. Reply to the letter “Pure or mixed type invasive lobular carcinoma; are they different from each other?”. Breast 2019; 43:151-152. [DOI: 10.1016/j.breast.2018.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 12/07/2018] [Indexed: 10/27/2022] Open
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Williams LA, Hoadley KA, Nichols HB, Geradts J, Perou CM, Love MI, Olshan AF, Troester MA. Differences in race, molecular and tumor characteristics among women diagnosed with invasive ductal and lobular breast carcinomas. Cancer Causes Control 2019; 30:31-39. [PMID: 30617775 PMCID: PMC6396692 DOI: 10.1007/s10552-018-1121-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 12/06/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The dominant invasive breast cancer histologic subtype, ductal carcinoma, shows intrinsic subtype diversity. However, lobular breast cancers are predominantly Luminal A. Both histologic subtypes show distinct relationships with patient and tumor characteristics, but it is unclear if these associations remain after accounting for intrinsic subtype. METHODS Generalized linear models were used to estimate relative frequency differences (RFDs) and 95% confidence intervals (95% CIs) for the associations between age, race, tumor characteristics, immunohistochemistry (IHC) and RNA-based intrinsic subtype, TP53 status, and histologic subtype in the Carolina Breast Cancer Study (CBCS, n = 3,182) and The Cancer Genome Atlas (TCGA, n = 808). RESULTS Relative to ductal tumors, lobular tumors were significantly more likely to be Luminal A [CBCS RNA RFD: 44.9%, 95% CI (39.6, 50.1); TCGA: RFD: 50.5%, 95% CI (43.9, 57.1)], were less frequent among young (≤ 50 years) and black women, were larger in size, low grade, less frequently had TP53 pathway defects, and were diagnosed at later stages. These associations persisted among Luminal A tumors (n = 242). CONCLUSIONS While histology is strongly associated with molecular characteristics, histologic associations with age, race, size, grade, and stage persisted after restricting to Luminal A subtype. Histology may continue to be clinically relevant among Luminal A breast cancers.
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Affiliation(s)
- Lindsay A Williams
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC, 27599, USA
| | - Katherine A Hoadley
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Hazel B Nichols
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC, 27599, USA
| | - Joseph Geradts
- Department of Population Sciences, City of Hope National Medical Center, Duarte, CA, 91010, USA
| | - Charles M Perou
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Michael I Love
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Andrew F Olshan
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC, 27599, USA
| | - Melissa A Troester
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC, 27599, USA.
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
- Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
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Metzger-Filho O, Ferreira AR, Jeselsohn R, Barry WT, Dillon DA, Brock JE, Vaz-Luis I, Hughes ME, Winer EP, Lin NU. Mixed Invasive Ductal and Lobular Carcinoma of the Breast: Prognosis and the Importance of Histologic Grade. Oncologist 2018; 24:e441-e449. [PMID: 30518616 DOI: 10.1634/theoncologist.2018-0363] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 08/31/2018] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The diagnosis of mixed invasive ductal and lobular carcinoma (IDC-L) in clinical practice is often associated with uncertainty related to its prognosis and response to systemic therapies. With the increasing recognition of invasive lobular carcinoma (ILC) as a distinct disease subtype, questions surrounding IDC-L become even more relevant. In this study, we took advantage of a detailed clinical database to compare IDC-L and ILC regarding clinicopathologic and treatment characteristics, prognostic power of histologic grade, and survival outcomes. MATERIALS AND METHODS In this retrospective cohort study, we identified 811 patients diagnosed with early-stage breast cancer with IDC-L or ILC. Descriptive statistics were performed to compare baseline clinicopathologic characteristics and treatments. Survival rates were subsequently analyzed using the Kaplan-Meier method and compared using the Cox proportional hazards model. RESULTS Patients with ILC had more commonly multifocal disease, low to intermediate histologic grade, and HER2-negative disease. Histologic grade was prognostic for patients with IDC-L but had no significant discriminatory power in patients with ILC. Among postmenopausal women, those with IDC-L had significantly better outcomes when compared with those with ILC: disease-free survival (DFS) and overall survival (OS; adjusted hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.31-0.95). Finally, postmenopausal women treated with an aromatase inhibitor had more favorable DFS and OS than those treated with tamoxifen only (OS adjusted HR, 0.50; 95% CI, 0.29-0.87), which was similar for both histologic types (p = .212). CONCLUSION IDC-L tumors have a better prognosis than ILC tumors, particularly among postmenopausal women. Histologic grade is an important prognostic factor in IDC-L but not in ILC. IMPLICATIONS FOR PRACTICE This study compared mixed invasive ductal and lobular carcinoma (IDC-L) with invasive lobular carcinomas (ILCs) to assess the overall prognosis, the prognostic role of histologic grade, and response to systemic therapy. It was found that patients with IDC-L tumors have a better prognosis than ILC, particularly among postmenopausal women, which may impact follow-up strategies. Moreover, although histologic grade failed to stratify the risk of ILC, it showed an important prognostic power in IDC-L, thus highlighting its clinical utility to guide treatment decisions of IDC-L. Finally, the disease-free survival advantage of adjuvant aromatase inhibitors over tamoxifen in ILC was consistent in IDC-L.
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Affiliation(s)
- Otto Metzger-Filho
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Arlindo R Ferreira
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Hospital de Santa Maria and Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Rinath Jeselsohn
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - William T Barry
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Deborah A Dillon
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jane E Brock
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Ines Vaz-Luis
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Melissa E Hughes
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Eric P Winer
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Nancy U Lin
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Wang K, Zhu GQ, Shi Y, Li ZY, Zhang X, Li HY. Long-Term Survival Differences Between T1-2 Invasive Lobular Breast Cancer and Corresponding Ductal Carcinoma After Breast-Conserving Surgery: A Propensity-Scored Matched Longitudinal Cohort Study. Clin Breast Cancer 2018; 19:e101-e115. [PMID: 30502219 DOI: 10.1016/j.clbc.2018.10.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 10/01/2018] [Accepted: 10/24/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND The role of histology subtype on the prognosis of T1-2 breast cancer patients receiving breast-conserving surgery (BCS) is not clear. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program was used to compare overall survival, second primary cancer-free survival (CFS), and local recurrence risk (LR) for patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), both receiving BCS. RESULTS The study enrolled 196,688 patients with T1-2 disease receiving BCS, including 12,906 with ILC and 183,782 with IDC. Patients with IDC showed higher unadjusted annual rates of BCS than ILC. Five- and 10-year estimated survival rates were, respectively, 92.06% and 86.14% in ILC, compared to 90.50% and 85.26% in IDC (P = .12). In multivariable Cox regression, ILC patients showed advantage over IDC in overall survival (hazard ratio [HR] = 0.93, P = .001), whereas no significant differences in CFS (HR = 1.03, P = .33) and LR (HR = 1.17, P = .06) were found, which were consistent with results from matched cohort. In subgroup analyses, patients with grade III ILC had poorer CFS (HR = 1.23, P = .009) and higher LR (HR = 1.59, P = .01) than IDC. CONCLUSION Histologic type is of prognostic importance in T1-2 patients receiving BCS, and surgeons should be cautious in performing BCS for individuals with grade III ILC.
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Affiliation(s)
- Kang Wang
- Department of Endocrine and Breast Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China, Fudan University, Shanghai, China
| | - Gui-Qi Zhu
- Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
| | - Yang Shi
- Division of Biostatistics and Data Science, Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA; Department of Epidemiology and Biostatistics, West China School of Public Health, West China Hospital, Sichuan University, Chengdu, China
| | - Zhu-Yue Li
- West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China; Institute of Hospital Management, West China Hospital, Sichuan University, Chengdu, China
| | - Xiang Zhang
- Department of Endocrine and Breast Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China, Fudan University, Shanghai, China.
| | - Hong-Yuan Li
- Department of Endocrine and Breast Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China, Fudan University, Shanghai, China.
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32
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Elzamly S, Badri N, Padilla O, Dwivedi AK, Alvarado LA, Hamilton M, Diab N, Rock C, Elfar A, Teleb M, Sanchez L, Nahleh Z. Epithelial-Mesenchymal Transition Markers in Breast Cancer and Pathological Responseafter Neoadjuvant Chemotherapy. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2018; 12:1178223418788074. [PMID: 30083055 PMCID: PMC6071152 DOI: 10.1177/1178223418788074] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 06/17/2018] [Indexed: 01/13/2023]
Abstract
The association between pathologic complete response (pCR) following to
neoadjuvant chemotherapy (NAC) and the improved survival in breast cancer has
been previously reported. The aim of this study was is to explore the expression
of several biomarkers described during epithelial-mesenchymal transition (EMT)
and the achievement of pCR in different molecular subtypes of breast cancer. We
identified archived pathology tissue from patients with breast cancer who
received NAC during the year 2014. We performed immunohistochemical analysis of
vimentin, nuclear factor κB (NF-κB), epidermal growth factor receptor (EGFR),
E-cadherin, estrogen receptor (ER), progesterone receptor, and Her2neu and
studied the association between the expression of these markers and pCR. A
Fisher exact test for categorical cofactors, an unpaired t test
and a nonparametric Wilcoxon test for continuous cofactors were used. The
results showed a significant expression of vimentin in triple-negative breast
cancer (TNBC; P = .023). An inverse correlation between
vimentin and the ER expression (P = .032) was observed. No
significant association was noted for vimentin, NF-κB, EGFR, and E-cadherin was
associated with pCR. This study suggests that the evaluated EMT related
biomarkers are not associated with pCR after NAC chemotherapy in an unselected
breast cancer population. Vimentin and NF-κB expressions were associated with
TNBC and could be further explored as potential therapeutic targets in this
subgroup. A prevalence of vimentin and NF-κB among Hispanic patients with breast
cancer warrants further investigation as a possibly contributing to the
prevalence of TNBC and adverse prognosis in this population.
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Affiliation(s)
- Shaimaa Elzamly
- Department of Pathology, Texas Tech University Health Sciences Center, El Paso, TX, USA.,Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt
| | - Nabeel Badri
- Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Osvaldo Padilla
- Department of Pathology, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Alok Kumar Dwivedi
- Division of Biostatistics and Epidemiology, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Luis A Alvarado
- Division of Biostatistics and Epidemiology, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Matthew Hamilton
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Nabih Diab
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Crosby Rock
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Ahmed Elfar
- Department of Nephrology, UT Southwestern Medical Center and Parkland Memorial Hospital, Dallas, TX, USA
| | - Marwa Teleb
- Department of Internal Medicine VA Hospital of North Texas, Dallas, TX, USA
| | - Luis Sanchez
- Department of Internal Medicine VA Hospital of North Texas, Dallas, TX, USA
| | - Zeina Nahleh
- Department of Hematology-Oncology, Maroone Cancer Center, Cleveland Clinic Florida, Weston, FL, USA
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33
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Williams LA, Butler EN, Sun X, Allott EH, Cohen SM, Fuller AM, Hoadley KA, Perou CM, Geradts J, Olshan AF, Troester MA. TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases. NPJ Breast Cancer 2018; 4:13. [PMID: 29951581 PMCID: PMC6018637 DOI: 10.1038/s41523-018-0067-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 05/18/2018] [Accepted: 05/29/2018] [Indexed: 01/08/2023] Open
Abstract
Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-based pathway methods capture functional status and may aid in understanding the role of TP53 function in racial disparities of breast cancer. TP53 status was assessed among invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008–2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer Genome Atlas (TCGA)). Frequency of TP53 status (IHC, RNA-based) was estimated in association with tumor characteristics, PAM50 intrinsic subtype, age, and race using relative frequency differences (RFDs) and 95% confidence intervals (95% CI) as the measure of association. Approximately 60% of basal-like tumors were TP53 protein positive (IHC), while nearly 100% were TP53 mutant-like (RNA). Luminal A tumors had low frequency of TP53 positivity (IHC: 7.9%) and mutant-like status (RNA: 1.7%). Mutant-like TP53 (RNA) was strongly associated with age ≤50 years, high tumor grade, advanced stage of disease, large tumor size, and basal-like and HER2 intrinsic subtypes. Black race was strongly associated with TP53 mutant-like status (RNA) (RFD: 24.8%, 95% CI: 20.5, 29.0) even after adjusting for age, grade, stage (RFD: 11.3%; 95% CI: 7.6, 15.0). Associations were attenuated and non-significant when measured by IHC. IHC-based TP53 status is an insensitive measurement of TP53 functional status. RNA-based methods suggest a role for TP53 in tumor prognostic features and racial disparities. RNA-based assays offer a more sensitive and clinically informative measure of mutations in the tumor suppressor TP53 among women with invasive breast cancer than do immunohistochemistry techniques that can only detect altered proteins. Using tumor samples from more than 1000 women enrolled in the Carolina Breast Cancer Study (CBCS), Melissa Troester from the University of North Carolina at Chapel Hill, USA, and coworkers assessed the functional status of TP53 via both classical immunohistochemistry methods and an RNA-based test of expression levels among 52 TP53-dependent genes. The results of the RNA analysis were strongly associated with younger age-of-onset, higher grade tumors, more advanced stage disease, larger tumor size, aggressive cancer subtypes and race—with more black women harboring TP53 mutant-like tumors than white women. By comparison, these associations were weaker or non-significant when using immunohistochemistry-based tests.
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Affiliation(s)
- Lindsay A Williams
- 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Ebonee N Butler
- 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Xuezheng Sun
- 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Emma H Allott
- 2Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Stephanie M Cohen
- 3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Ashley M Fuller
- 4Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Katherine A Hoadley
- 3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA.,5Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Charles M Perou
- 5Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Joseph Geradts
- 6Department of Pathology, Dana-Farber Cancer Institute, Boston, MA 02115 USA
| | - Andrew F Olshan
- 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Melissa A Troester
- 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA.,3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA.,4Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
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34
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Da Ros L, Moretti A, Querzoli P, Pedriali M, Lupini L, Bassi C, Carcoforo P, Negrini M, Frassoldati A. HER2-Positive Lobular Versus Ductal Carcinoma of the Breast: Pattern of First Recurrence and Molecular Insights. Clin Breast Cancer 2018; 18:e1133-e1139. [PMID: 29759595 DOI: 10.1016/j.clbc.2018.04.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 12/29/2017] [Accepted: 04/08/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Infiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC). PATIENTS AND METHODS We retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies. A gene-mutation analysis was performed in a subset of patients. RESULTS Two hundred ninety-one patients (88.7%) had IDC and 37 patients (11.3%) ILC. ILC resulted more frequently in multicenter (24.3% vs. 6.5%, P < .0001) and node-positive (54.1% vs. 45%, P = .013) disease of lower proliferative activity (Mib1 < 20%: 51.4% vs. 22.3%, P < .0001) and lower histologic grade (grade 3: 32.4% vs. 57.4%, P = .038). Disease recurred in 57 patients (17.4%) and involved the bone in 40% of ILC patients (vs. 17% of IDC patients) and the viscera in 30% of ILC patients (vs. 59.6% of IDC patients). No difference in the recurrence rate between the 2 histologies was observed in patients treated with adjuvant trastuzumab (12.5% of ILC patients and 8.3% of IDC patients). Exploratory molecular analysis revealed a higher frequency of mutations in ILC, with more cases of multiple mutations. CONCLUSION HER2-positive ILC shows different biological behavior than IDC, with a possible higher mutation load. Despite lower proliferation activity and estrogen receptor expression in ILC breast cancer, trastuzumab is clearly an effective therapy for this histologic subtype.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents, Immunological/therapeutic use
- Breast Neoplasms/drug therapy
- Breast Neoplasms/genetics
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/drug therapy
- Carcinoma, Ductal, Breast/genetics
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Lobular/drug therapy
- Carcinoma, Lobular/genetics
- Carcinoma, Lobular/pathology
- Disease-Free Survival
- Female
- Humans
- Middle Aged
- Mutation
- Neoplasm Recurrence, Local/epidemiology
- Receptor, ErbB-2
- Retrospective Studies
- Trastuzumab/therapeutic use
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Affiliation(s)
- Lucia Da Ros
- Division of Clinical Oncology, St Anna University Hospital, Ferrara, Italy
| | - Anna Moretti
- Division of Clinical Oncology, St Anna University Hospital, Ferrara, Italy
| | | | | | - Laura Lupini
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Cristian Bassi
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Paolo Carcoforo
- Surgery Department, St Anna University Hospital, Ferrara, Italy
| | - Massimo Negrini
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
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35
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McCart Reed AE, Kutasovic JR, Nones K, Saunus JM, Da Silva L, Newell F, Kazakoff S, Melville L, Jayanthan J, Vargas AC, Reid LE, Beesley J, Chen XQ, Patch AM, Clouston D, Porter A, Evans E, Pearson JV, Chenevix-Trench G, Cummings MC, Waddell N, Lakhani SR, Simpson PT. Mixed ductal-lobular carcinomas: evidence for progression from ductal to lobular morphology. J Pathol 2018; 244:460-468. [PMID: 29344954 PMCID: PMC5873281 DOI: 10.1002/path.5040] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 01/07/2018] [Accepted: 01/09/2018] [Indexed: 12/15/2022]
Abstract
Mixed ductal–lobular carcinomas (MDLs) show both ductal and lobular morphology, and constitute an archetypal example of intratumoural morphological heterogeneity. The mechanisms underlying the coexistence of these different morphological entities are poorly understood, although theories include that these components either represent ‘collision’ of independent tumours or evolve from a common ancestor. We performed comprehensive clinicopathological analysis of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2) the E‐cadherin–catenin complex was normal in the ductal component in 77.6% of tumours; and (3) in the lobular component, E‐cadherin was almost always aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma (ILC), where E‐cadherin is typically absent. Comparative genomic hybridization and multiregion whole exome sequencing of four representative cases revealed that all morphologically distinct components within an individual case were clonally related. The mutations identified varied between cases; those associated with a common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated with clonal divergence included CDH1 and ESR1. Together, these data support a model in which separate morphological components of MDLs arise from a common ancestor, and lobular morphology can arise via a ductal pathway of tumour progression. In MDLs that present with LCIS and DCIS, the clonal divergence probably occurs early, and is frequently associated with complete loss of E‐cadherin expression, as in ILC, whereas, in the majority of MDLs, which present with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular phenotype occurs late in tumour evolution, and is associated with aberrant expression of E‐cadherin. The mechanisms driving the phenotypic change may involve E‐cadherin–catenin complex deregulation, but are yet to be fully elucidated, as there is significant intertumoural heterogeneity, and each case may have a unique molecular mechanism. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Amy E McCart Reed
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.,QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Jamie R Kutasovic
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.,QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Katia Nones
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Jodi M Saunus
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Leonard Da Silva
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Felicity Newell
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | | | - Lewis Melville
- Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Janani Jayanthan
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Ana Cristina Vargas
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Lynne E Reid
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | | | - Xiao Qing Chen
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | | | | | - Alan Porter
- The Wesley Breast Clinic, The Wesley Hospital, Brisbane, Australia
| | - Elizabeth Evans
- The Wesley Breast Clinic, The Wesley Hospital, Brisbane, Australia
| | - John V Pearson
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | | | - Margaret C Cummings
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.,Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Nicola Waddell
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Sunil R Lakhani
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.,Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Peter T Simpson
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.,QIMR Berghofer Medical Research Institute, Brisbane, Australia
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36
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Williams LA, Nichols HB, Hoadley KA, Tse CK, Geradts J, Bell ME, Perou CM, Love MI, Olshan AF, Troester MA. Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study. Cancer Causes Control 2018; 29:25-32. [PMID: 29124544 PMCID: PMC5903274 DOI: 10.1007/s10552-017-0977-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 10/30/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype. METHODS Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+). RESULTS In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype. CONCLUSIONS Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.
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Affiliation(s)
- Lindsay A Williams
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Hazel B Nichols
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Katherine A Hoadley
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Chiu Kit Tse
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Joseph Geradts
- Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA
| | - Mary Elizabeth Bell
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Charles M Perou
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Michael I Love
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Andrew F Olshan
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Melissa A Troester
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
- Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
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37
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Yang M, Bao W, Zhang X, Kang Y, Haffty B, Zhang L. Short-term and long-term clinical outcomes of uncommon types of invasive breast cancer. Histopathology 2017; 71:874-886. [DOI: 10.1111/his.13328] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 07/21/2017] [Accepted: 07/24/2017] [Indexed: 11/30/2022]
Affiliation(s)
- Mu Yang
- Department of Pathology; University Medical Center of Princeton; Plainsboro NJ UK
| | - Wei Bao
- Department of Epidemiology; College of Public Health; University of Iowa; Iowa City; IA USA
| | - Xinmin Zhang
- Department of Pathology; Cooper University Hospital; Camden NJ USA
| | - Yibin Kang
- Department of Molecular Biology; Princeton University; Princeton NJ USA
| | - Bruce Haffty
- Rutgers Cancer Institute of New Jersey; New Brunswick NJ USA
| | - Lanjing Zhang
- Department of Pathology; University Medical Center of Princeton; Plainsboro NJ UK
- Rutgers Cancer Institute of New Jersey; New Brunswick NJ USA
- Department of Biological Sciences; Rutgers University; Newark NJ USA
- Department of Chemical Biology; Ernest Mario School of Pharmacy, Rutgers University; Piscataway NJ USA
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38
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Fatty acid synthase affects expression of ErbB receptors in epithelial to mesenchymal transition of breast cancer cells and invasive ductal carcinoma. Oncol Lett 2017; 14:5934-5946. [PMID: 29113229 PMCID: PMC5661422 DOI: 10.3892/ol.2017.6954] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2015] [Accepted: 06/09/2017] [Indexed: 02/05/2023] Open
Abstract
The aim of the present study was to investigate changes in the expression of ErbBs during epithelial-mesenchymal transition (EMT) of breast cancer cells and its association with the expression of fatty acid synthase (FASN). MCF-7-MEK5 cells were used as the experimental model, while MCF-7 cells were used as a control. Tumor cells were implanted into nude mice for in vivo analysis. Cerulenin was used as a FASN inhibitor. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect expression levels of FASN and ErbB1-4. Immunohistochemistry was used to detect the expression of FASN and ErbB1-4 in 58 invasive ductal carcinomas (IDC), as well as their association with clinicopathological characteristics. The expression of FASN and ErbB1-4 in MCF-7-MEK5 cells and tumor tissues increased significantly compared with controls (P<0.001). Inhibition of FASN by cerulenin resulted in a significant decrease in expression of ErbB1, 2 and 4 (P<0.001), whereas there was no evident change in ErbB3. In IDC samples, the expression of FASN and ErbB1-4 increased considerably in lymph node metastases compared with non-lymph node metastases (P<0.05). ErbB2 expression increased in advanced clinical stages (II, III and IV) of IDC and in tumors with larger diameters (P<0.05). The expression of ErbB3 increased in ER-positive tumors (P<0.05). Additionally, a positive association between the expression of FASN and ErbB1, 2 and 4 was observed (P<0.05). FASN activates ErbB1, 2 and 4, and their dimers, which are polymerized via the microstructural domain of the cell membrane. This may initiate EMT and consequentlyincrease the invasion and migration of cancer cells. However, ErbB3 may also affect tumor progression via a FASN-independent pathway.
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39
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Xiao Y, Ma D, Ruan M, Zhao S, Liu XY, Jiang YZ, Shao ZM. Mixed invasive ductal and lobular carcinoma has distinct clinical features and predicts worse prognosis when stratified by estrogen receptor status. Sci Rep 2017; 7:10380. [PMID: 28871133 PMCID: PMC5583173 DOI: 10.1038/s41598-017-10789-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 08/14/2017] [Indexed: 12/15/2022] Open
Abstract
In order to investigate clinicopathological characteristics and prognosis of mixed invasive ductal and lobular carcinoma (IDC-L), 209,109 primary breast cancer patients diagnosed with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) or IDC-L were included. It was found that IDC-L patients had lower tumor grade and higher hormone receptor positive proportions than IDC patients. Moreover, IDC-L patients were younger and had a similar hormone receptor status compared with ILC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of IDC-L patients was significantly better than IDC patients (P < 0.001) and tended to be better than ILC patients (P = 0.166). However, after adjusting for clinicopathological factors, survival advantage of IDC-L disappeared. Subgroup analysis indicated that IDC-L had higher hazard ratios (HRs) than IDC in grade 1, grade 2, ER-positive and ER-negative subgroups. Survival analysis in ER-positive and ER-negative subgroups showed that IDC-L predicted a worse prognosis than IDC. In conclusion, IDC-L is a distinct histological subtype compared with IDC and ILC. Lower grade and higher ER-positive proportions mainly contribute to its better prognosis. In both ER-positive and ER-negative subgroups, IDC-L predicts worse prognosis than IDC, which suggested the inadequacy of IDC-based therapy and the need of escalated therapy.
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Affiliation(s)
- Yi Xiao
- Department of Breast Surgery, Fudan University Shanghai Cancer Center; Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong-an Road, Shanghai, 200032, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Ding Ma
- Department of Breast Surgery, Fudan University Shanghai Cancer Center; Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong-an Road, Shanghai, 200032, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Miao Ruan
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.,Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Shen Zhao
- Department of Breast Surgery, Fudan University Shanghai Cancer Center; Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong-an Road, Shanghai, 200032, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Xi-Yu Liu
- Department of Breast Surgery, Fudan University Shanghai Cancer Center; Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong-an Road, Shanghai, 200032, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Yi-Zhou Jiang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center; Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong-an Road, Shanghai, 200032, People's Republic of China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
| | - Zhi-Ming Shao
- Department of Breast Surgery, Fudan University Shanghai Cancer Center; Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong-an Road, Shanghai, 200032, People's Republic of China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. .,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
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40
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Orsini M, Trétarre B, Daurès JP, Bessaoud F. Individual socioeconomic status and breast cancer diagnostic stages: a French case–control study. Eur J Public Health 2016; 26:445-50. [DOI: 10.1093/eurpub/ckv233] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Chung A, Gangi A, Amersi F, Bose S, Zhang X, Giuliano A. Impact of Consensus Guidelines by the Society of Surgical Oncology and the American Society for Radiation Oncology on Margins for Breast-Conserving Surgery in Stages 1 and 2 Invasive Breast Cancer. Ann Surg Oncol 2015; 22 Suppl 3:S422-7. [PMID: 26310280 DOI: 10.1245/s10434-015-4829-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Indexed: 11/18/2022]
Abstract
BACKGROUND This study aimed to evaluate the impact that the release of consensus guidelines for margins in breast-conserving surgery (BCS) had on re-excision rates. METHODS A retrospective review examined a prospectively maintained database of patients who had operable invasive breast cancer treated with BCS at the authors' institution. The patients were divided into two groups: (1) those with a diagnosis determined from 1 July 2011 to 31 July 2013 (before release of the guidelines) and (2) those with a diagnosis determined from 1 February 2014 to 31 July 2014 (after release of the guidelines). The groups were evaluated with respect to patient and tumor characteristics, re-excision rates, and reasons for re-excision. RESULTS A total of 846 cases of BCS were managed: 597 in group 1 and 249 in group 2. Re-excision rates were significantly reduced after release of the consensus guidelines (p = 0.03). Re-excisions were performed for 115 (19 %) of 597 patients in group 1 and 32 (13 %) of 249 patients in group 2. After release of the guidelines, re-excisions were performed for positive margins, as defined by the consensus statement, in 25 (78 %) of 32 cases. The two groups did not differ significantly in terms of age, tumor size, grade, nodal status, estrogen receptor status, progesterone receptor status, or human epidermal growth factor receptor 2 status. Group 1 had more tumors of mixed ductal and lobular histology than group 2, and group 2 had more lobular tumors than group 1 (p = 0.02). CONCLUSIONS The consensus guidelines on margins for BCS were applied for 78 % of the patients who underwent re-excision and resulted in a significant reduction in re-excision rates.
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Affiliation(s)
- A Chung
- Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
| | - A Gangi
- Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - F Amersi
- Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - S Bose
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - X Zhang
- Department of Biostatistics, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - A Giuliano
- Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin. Breast Cancer Res Treat 2015; 149:555-64. [DOI: 10.1007/s10549-015-3273-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 01/08/2015] [Indexed: 10/24/2022]
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Kamdje AHN, Etet PFS, Vecchio L, Tagne RS, Amvene JM, Muller JM, Krampera M, Lukong KE. New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers. World J Clin Cases 2014; 2:769-786. [PMID: 25516852 PMCID: PMC4266825 DOI: 10.12998/wjcc.v2.i12.769] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Revised: 07/12/2014] [Accepted: 09/23/2014] [Indexed: 02/05/2023] Open
Abstract
Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy, including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin, Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.
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Wong H, Lau S, Cheung P, Wong TT, Parker A, Yau T, Epstein RJ. Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy. BMC Cancer 2014; 14:826. [PMID: 25385074 PMCID: PMC4236427 DOI: 10.1186/1471-2407-14-826] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Accepted: 10/23/2014] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity. METHODS The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed. RESULTS Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6). CONCLUSION These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.
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Affiliation(s)
| | | | | | | | | | - Thomas Yau
- Division of Hematology/Oncology, University Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
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New Therapeutic Approaches for Invasive Lobular Carcinoma. CURRENT BREAST CANCER REPORTS 2014. [DOI: 10.1007/s12609-014-0158-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Tajiri R, Inokuchi M, Sawada-Kitamura S, Kawashima H, Nakamura R, Oyama T, Dobashi Y, Ooi A. Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization. Pathol Int 2014; 64:231-6. [PMID: 24888777 DOI: 10.1111/pin.12158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2014] [Accepted: 03/25/2014] [Indexed: 11/29/2022]
Abstract
A needle biopsy of a mass in the right breast of a 36-year-old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E-cadherin-negative invasive lobular carcinoma (ILC), and the rest was ERBB2-positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analyses revealed that ILC and IDC shared high-level amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR-type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.
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Affiliation(s)
- Ryosuke Tajiri
- Department of Molecular and Cellular Pathology, Kanazawa University, Ishikawa
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