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Voutsadakis IA. Breast Cancers With Intermediate Estrogen Receptor Expression: Characteristics, Prognosis and Treatment. Clin Breast Cancer 2025; 25:214-222. [PMID: 39710525 DOI: 10.1016/j.clbc.2024.11.020] [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: 06/21/2024] [Revised: 11/27/2024] [Accepted: 11/28/2024] [Indexed: 12/24/2024]
Abstract
In the era of personalized oncology biomarkers that identify subgroups of specific cancers and help predict response to specific therapies are critical tools for prognosis determination and therapeutic decisions. The Estrogen Receptor (ER) had been one of the first biomarkers used in breast cancer and has helped advance the field of breast oncology by contributing to the success of hormonal therapies for the ER positive subgroup of the disease. Expression of the receptor in 1% or more of tumor cells in immunohistochemical sections define currently the ER positive subgroup of breast cancers, which may be treated with regimens that include hormonal inhibitors. The highest sensitivity and benefit of hormonal therapies is observed in cancers with robust ER expression (in 90% to 100% of tumor cells). However, it has become clear that the subgroup of breast cancers with low ER expression (in 1% to 10% of tumor cells) behaves similarly to ER negative breast cancers and has an inferior response to hormonal therapies. The behavior of the rest of ER positive breast cancers with an intermediate ER expression between these 2 extremes (ER expression between 10% and 90%) is less well described and their response to estrogen targeting therapies is less clear. Breast cancers with intermediate ER expression represent a small subgroup of ER positive breast cancers and the wide range of expressions suggests heterogeneity. This review will discuss this subgroup of ER positive breast cancers and examine their genomic landscape and therapeutic repercussions.
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Affiliation(s)
- Ioannis A Voutsadakis
- Algoma District Cancer Program, Sault Area Hospital, Sault Ste Marie, Ontario, Canada; Division of Clinical Sciences, Section of Internal Medicine, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
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Vila J, Farante G, Ripoll-Orts F, Lissidini G, Nicosia L, Lazzeroni M, Frassoni S, Bagnardi V, Rodríguez Del Busto B, Bonanni B, Cassano E, Veronesi P. A retrospective study evaluating surgical upstaging rates in low-risk DCIS patients meeting the eligibility criteria for active surveillance trials. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109716. [PMID: 40101683 DOI: 10.1016/j.ejso.2025.109716] [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: 11/01/2024] [Revised: 02/03/2025] [Accepted: 02/19/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND The management of small low-to-medium grade ductal carcinoma in situ (DCIS) on core biopsy remains controversial. Four international studies are currently recruiting highly selected low-risk DCIS patients to compare active surveillance ( ± hormonal treatment) versus conventional treatment. In this study, we aim to determine the upstaging rate at a tertiary center among low-risk DCIS patients meeting eligibility criteria for active surveillance trials. METHODS A retrospective study was undertaken of all patients diagnosed with small (<2 cm) low-medium grade DCIS patients at the European Institute of Oncology, Milan, from 2009 to 2019. All cases were classified as eligible based on the COMET, LORIS, LORD and LORETTA DCIS studies, according to their respective inclusion criteria. RESULTS We identified 351 patients from a prospectively maintained database who were diagnosed with G1-G2 DCIS on core biopsy, with a median age of 55 years (range 45-82). The overall upstage/upgrade rate was 23.6 %. Of the 351 patients, sixty-four (18.2 %) were upstaged to invasive disease and nine-teen (5.4 %) were upgraded to grade 3 DCIS. It is worth noting a rate of 7.9 % of patients with >pT1c and 2.3 % of patients with nodal involvement at the time of surgery. On both univariable and multivariable analysis, no specific variable was found to be a statistically significant predictor for upstaging. CONCLUSION Over 23 % of patients with low-risk DCIS may be upgraded or upstaged at resection, especially towards invasive carcinoma (18.2 % of cases were staged to invasive cancer at surgical resection). These data suggest that active surveillance is not warranted in this highly selected group of low-risk DCIS patients. Stricter selection criteria must be considered to ensure appropriate treatment of such patients.
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Affiliation(s)
- Jose Vila
- Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy; Breast Surgery Department, La Fe University Hospital, Valencia, Spain
| | - Gabriel Farante
- Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy
| | | | - Germana Lissidini
- Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy
| | - Luca Nicosia
- Breast Imaging Division, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Matteo Lazzeroni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Samuele Frassoni
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
| | | | - Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Enrico Cassano
- Breast Imaging Division, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Paolo Veronesi
- Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, Faculty of Medicine, University of Milan, Milan, Italy
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DiGregorio N, Munter-Young R. Developing & Validating a Clinical Decision Support Tool for ER-Targeted PET Imaging With 16α-18F-Fluoro-17β-Fluoroestradiol. Clin Breast Cancer 2025; 25:133-140.e1. [PMID: 39613672 DOI: 10.1016/j.clbc.2024.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 10/09/2024] [Accepted: 10/19/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND Estrogen receptor (ER) status in breast cancer (BC) is routinely determined by immunohistochemistry (IHC); however, this technique is not without limitations, including false results. Imaging of CeriannaTM (fluoroestradiol F18) injection provides high diagnostic accuracy of ER expression, supplementing information from biopsy. A Clinical Decision Support (CDS) tool was developed to better assess its clinical usefulness in metastatic and recurrent breast cancer management. This study evaluated a conceptual tool that reflects clinical practice variables. METHODS Individual patient characteristics - candidacy for therapeutic treatment and rate of recurrence - determined initial eligibility. The CDS tool uses rules (IF-THEN statements) to produce an output on the diagnostic accuracy of ER status based on tumor burden, anatomical location(s) of metastasis, heterogeneity, and confidence in sample collection & pathology accuracy (CSC & PA). An Excel-based probability decision tree calculates the accuracy of ER expression. RESULTS 360 oncologists in the United States participated in the survey study. 223 respondents identified as medical oncologists (62%), 77 as clinical oncologists (21%), and 60 as hematologic oncologists (17%). 93% of respondents found the CDS tool intuitive and easy to follow with medical and clinical oncologists favoring the tool more than hematologic oncologists. Individual CDS attributes - clinical criteria, diagnostic comparator, true positive and true negative, patient inclusion and exclusion, and clinical patient level inputs - were tested with overall positive feedback. CONCLUSIONS Based on respondent feedback, further development of CDS tools are warranted for potential use in patients' diagnostic workup.
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Mais DD, Nazarullah AN, Guidi AJ, Dintzis S, Blond BJ, Long TA, Coulter SN, Brown RW. Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Expression Rates in Invasive Breast Carcinoma: A Study of 21 Institutions. Arch Pathol Lab Med 2025; 149:8-13. [PMID: 38631690 DOI: 10.5858/arpa.2022-0384-cp] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2024] [Indexed: 04/19/2024]
Abstract
CONTEXT.— Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks. OBJECTIVE.— To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories. DESIGN.— Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates. RESULTS.— A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 3+) rate was 9.0%. The aggregate HER2 equivocal (score 2+) rate was 14.5%. Of 81 equivocal (score 2+) cases, 70 (86.4%) were nonamplified. CONCLUSIONS.— The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.
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Affiliation(s)
- Daniel D Mais
- From the Department of Pathology, University of Louisville School of Medicine, Louisville, Kentucky (Mais)
| | - Alia N Nazarullah
- the Department of Pathology, University of Texas Long School of Medicine, San Antonio (Nazarullah)
| | - Anthony J Guidi
- the Department of Pathology, Brigham and Women's Faulkner Hospital, Boston, Massachusetts (Guidi)
| | - Suzanne Dintzis
- the Department of Pathology, University of Washington, Seattle (Dintzis)
| | - Barbara J Blond
- the Department of Biostatistics, College of American Pathologists, Northfield, Illinois (Blond, Long, Coulter)
| | - Thomas A Long
- the Department of Biostatistics, College of American Pathologists, Northfield, Illinois (Blond, Long, Coulter)
| | - Suzanne N Coulter
- the Department of Biostatistics, College of American Pathologists, Northfield, Illinois (Blond, Long, Coulter)
| | - Richard W Brown
- the Department of Pathology, Memorial Hermann Hospital, Houston, Texas (Brown)
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Das S, Pattnaik G, Pattanaik S, Jena BR, Satapathy BS, Pradhan A. Envisioning Clinical Management of Breast Cancer: a Comprehensive Review. Curr Drug Discov Technol 2025; 22:e290424229495. [PMID: 38685777 DOI: 10.2174/0115701638300812240417055802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 02/29/2024] [Accepted: 03/12/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Background: Coming to the edge of disease manufacturing in the twenty-- first-century, breast cancer occupies a terrifying scenario in the globe, especially in adult women. Its curiosity endeavours remarkable advances made during the past decennaries for cancer treatment and diagnosis. OBJECTIVE It accounts for the fifth leading cause of transience, killing approximately 570,000 people per annum. To reduce the prognosis of clinical oncological development with the application of a new chemical entity, some of the critical challenges, like active pharmaceutical ingredients with high chemical resistance, extreme side effects, and high treatment costs are some of the limitations in the curbing aspects of breast melanoma. METHODS In cancer research, hence, the development of drugs that are safe, efficient, and cost-effective remains a 'Holy Grail' that may be considered as a boon to target the malignant tissues with novel therapeutics devices. RESULTS Through the findings on overcoming the drawbacks of traditional methods, researchers have given special attention to cancer-preventive and theranostic approaches based on some novel drug delivery systems. CONCLUSION The present study forecasts the wide-ranging modern applications, and on developing some novel liposomal drug delivery therapy against breast cancer.
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Affiliation(s)
- Shubhashree Das
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Jatani, 752050, Odisha, India
| | - Gurudutta Pattnaik
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Jatani, 752050, Odisha, India
| | - Sovan Pattanaik
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan Deemed to be University, Bhubaneswar, Jatani, 752050, Odisha, India
| | - Bikash Ranjan Jena
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Jatani, 752050, Odisha, India
| | - Bhabani Sankar Satapathy
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan Deemed to be University, Bhubaneswar, Jatani, 752050, Odisha, India
| | - Ayushi Pradhan
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Jatani, 752050, Odisha, India
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Fohlin H, Nordenskjöld A, Rosell J, Fernö M, Fornander T, Rydén L, Skoog L, Nordenskjöld B, Stål O. Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up. Acta Oncol 2024; 63:535-541. [PMID: 38967128 PMCID: PMC11332493 DOI: 10.2340/1651-226x.2024.40493] [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: 04/05/2024] [Accepted: 06/21/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. PATIENTS AND METHODS Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. RESULTS After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.
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Affiliation(s)
- Helena Fohlin
- Regional Cancer Center South-East Sweden and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
| | - Anna Nordenskjöld
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg Sweden
| | - Johan Rosell
- Regional Cancer Center South-East Sweden and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Mårten Fernö
- Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Tommy Fornander
- Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
| | - Lisa Rydén
- Department of Clinical Sciences Lund, Division of Surgery, Lund University, Lund, Sweden
| | - Lambert Skoog
- Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
| | - Bo Nordenskjöld
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Olle Stål
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Li BC, Hammond S, Parwani AV, Shen R. Artificial intelligence algorithm accurately assesses oestrogen receptor immunohistochemistry in metastatic breast cancer cytology specimens: A pilot study. Cytopathology 2024; 35:464-472. [PMID: 38519745 DOI: 10.1111/cyt.13373] [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: 12/24/2023] [Revised: 02/09/2024] [Accepted: 03/02/2024] [Indexed: 03/25/2024]
Abstract
OBJECTIVE The Visiopharm artificial intelligence (AI) algorithm for oestrogen receptor (ER) immunohistochemistry (IHC) in whole slide images (WSIs) has been successfully validated in surgical pathology. This study aimed to assess its efficacy in cytology specimens. METHODS The study cohort comprised 105 consecutive cytology specimens with metastatic breast carcinoma. ER IHC WSIs were seamlessly integrated into the Visiopharm platform from the Image Management System (IMS) during our routine digital workflow, and an AI algorithm was employed for analysis. ER AI scores were compared with pathologists' manual consensus scores. Optimization steps were implemented and evaluated to reduce discordance. RESULTS The overall concordance between pathologists' scores and AI scores was excellent (99/105, 94.3%). Six cases exhibited discordant results, including two false-negative (FN) cases due to abundant histiocytes incorrectly counted as negatively stained tumour cells by AI, two FN cases owing to weak staining, and two false-positive (FP) cases where pigmented macrophages were erroneously counted as positively stained tumour cells by AI. The Pearson correlation coefficient of ER-positive percentages between pathologists' and AI scores was 0.8483. Optimization steps, such as lowering the cut-off threshold and additional training using higher input magnification, significantly improved accuracy. CONCLUSIONS The automated ER AI algorithm demonstrated excellent concordance with pathologists' assessments and accurately differentiated ER-positive from ER-negative metastatic breast carcinoma cytology cases. However, precision in identifying tumour cells in cytology specimens requires further enhancement.
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Affiliation(s)
- Brenna C Li
- Dublin Jerome High School, Dublin, Ohio, USA
| | - Scott Hammond
- Department of Pathology, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA
| | - Anil V Parwani
- Department of Pathology, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA
| | - Rulong Shen
- Department of Pathology, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA
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Schandiz H, Farkas L, Park D, Liu Y, Andersen SN, Geisler J, Sauer T. Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components. Front Oncol 2024; 14:1347166. [PMID: 39011488 PMCID: PMC11247389 DOI: 10.3389/fonc.2024.1347166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 06/04/2024] [Indexed: 07/17/2024] Open
Abstract
Objective In this study, we investigated pivotal molecular markers in human high-grade breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) was measured among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched and triple-negative). Methods In total, 357 DCIS cases were classified into respective subtypes, according to the 2013 St. Gallen guidelines. Each subtype was categorized into three subcategories: "Pure" (those without an invasive component), "W/invasive" (those with an invasive component), and "All" (the entire group of the given subtype). ER and PR expression were registered as intervals. Equivocal HER2 immunohistochemistry (IHC) cases (2+) were further investigated using dual-color in situ hybridization. Results The majority of patients (71%) were over the age of 50. We discovered no significant differences in the proportion of age between the "Pure" and "W/invasive" groups. There was no significant difference in ER/PR expression between "Pure" luminal subtypes of DCIS and "W/invasive" cases. We compared the HER2 IHC scores of "0", "1+", and "2+" among LumA and LumB HER2 subtypes and identified no statistically significant differences between "Pure" and "W/invasive" (p = 0.603). ER and PR expression ≥ 50% cutoff value was present in > 90% of all LumA cases. The incidences of cases with ER expression at cutoff values of < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). The proportion of cases with PR expression < 20% showed significant differences in the various luminal subtypes. In luminal B subtypes, low PR expression (< 20%) was significantly associated with both strong HER2 expression (3+) and the presence of an invasive component (p = 0.0001 and p = 0.0365, respectively). Conclusions ER and PR expression at ≥ 50% cutoff values were found in more than 90% of LumA cases. Samples with ER < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). Low PR expression in high-grade DCIS was strongly associated with HER2 overexpression (3+) and an invasive component (p = 0.0001 and p = 0.0365, respectively).
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Affiliation(s)
- Hossein Schandiz
- Department of Oncology, Akershus University Hospital (AHUS), Lorenskog, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Lorant Farkas
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - Daehoon Park
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - Yan Liu
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital (AHUS), Lorenskog, Norway
| | - Solveig N Andersen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Jürgen Geisler
- Department of Oncology, Akershus University Hospital (AHUS), Lorenskog, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Torill Sauer
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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You YH, Kim MK, Lee JY. Prognosis and Adjusting Factors in Elderly Patients With Triple-Negative Breast Cancer: Comparing With Young and Middle Age Groups. Clin Breast Cancer 2024; 24:e258-e265. [PMID: 38413338 DOI: 10.1016/j.clbc.2024.01.016] [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: 08/27/2023] [Revised: 11/28/2023] [Accepted: 01/25/2024] [Indexed: 02/29/2024]
Abstract
PURPOSE Proper breast cancer screening and treatment should be considered in the elderly population; however, some tend to be less proactive. Our study aimed to investigate the impact of old age on treatment and prognosis in triple-negative breast cancer (TNBC). METHOD The study included patients with primary TNBC stage I-III diagnosed from 2002 to 2019 in single institution and retrospectively analyzed. We defined young (< 40 years), middle and old (> 70 years) groups. Clinicopathological factors, treatment, and prognosis were analyzed according to age group of TNBC patients. RESULT TNBC patients aged 70 and above were 3.3 times more likely (P = .019) to have lymph node metastasis at the time of diagnosis compared to younger patients, but were found to be 0.24 times less likely to receive chemotherapy. (P = .003) Old TNBC patients have an expected likelihood 2.2 times higher of undergoing mastectomy rather than breast-conserving surgery. (P = .042) The 5-year prognosis is poorer in young and old group. (61%, 86%, and 65% in young, middle, and old groups). (P < .001). In subanalysis, old group of stages I and II received fewer chemotherapy compared to youngers (P < .05), but not in stage III. In Cox regression analysis, age and stage had significant impact on prognosis (hazard ratio 2-3), but treatment factors did not. However, in stratified analysis of adjuvant therapy and stage, prognosis of Old TNBC patients in stage II was improved when they underwent neo or adjuvant chemotherapy. CONCLUSION TNBC presents challenges in older patients, who receive less aggressive treatment and have poorer outcomes. The primary cause of poor prognosis in old TNBC patients is the high disease stage at diagnosis, underscoring the need for promotion and education on early screening. Additionally, it is suggested that a more proactive approach to adjuvant chemotherapy is necessary for stage II old TNBC patients.
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Affiliation(s)
- Yong Ho You
- Department of Surgery, Chung-Ang University College of Medicine, Dongjak-gu, Seoul, Republic of Korea
| | - Min Kyoon Kim
- Department of Surgery, Chung-Ang University College of Medicine, Dongjak-gu, Seoul, Republic of Korea.
| | - Joo Yun Lee
- College of Nursing, Gachon University, Yeonsu-gu, Incheon, Republic of Korea.
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Makhlouf S, Quinn C, Toss M, Alsaleem M, Atallah NM, Ibrahim A, Rutland CS, Mongan NP, Rakha EA. Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance. Eur J Cancer 2024; 197:113473. [PMID: 38103327 DOI: 10.1016/j.ejca.2023.113473] [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: 09/16/2023] [Revised: 12/04/2023] [Accepted: 12/04/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND Oestrogen receptor (ER) positive breast cancer (BC) patients are eligible for endocrine therapy (ET), regardless of ER immunohistochemical expression level. There is a wide spectrum of ER expression and the response to ET is not uniform. This study aimed to assess the clinical and molecular consequences of ER heterogeneity with respect to ET-response. METHODS ER expression, categorised by percentage and staining intensity in a large BC cohort (n = 7559) was correlated with clinicopathological parameters and patient ET response. The Cancer Genome Atlas Data BC cohort (n = 1047) was stratified by ER expression and transcriptomic analysis completed to better understand the molecular basis of ER heterogeneity. RESULTS The quantitative proportional increase in ER expression was positively associated with favourable prognostic parameters. Tumours with 1-9% ER expression were characteristically similar to ER-negative (<1%) tumours. Maximum ET-response was observed in tumours with 100% ER expression, with responses significantly different to tumours exhibiting ER at < 100% and significantly decreased survival rates were observed in tumours with 50% and 10% of ER expression. The Histochemical-score (H-score), which considers both staining intensity and percentage, added significant prognostic value over ER percentage alone with significant outcome differences observed at H-scores of 30, 100 and 200. There was a positive correlation between ER expression and ESR1 mRNA expression and expression of ER-regulated genes. Pathway analysis identified differential expression in key cancer-related pathways in different ER-positive groups. CONCLUSION ET-response is statistically proportionally related to ER expression with significant differences observed at 10%, 50% and 100%. The H-score adds prognostic and predictive information.
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Affiliation(s)
- Shorouk Makhlouf
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Cecily Quinn
- Irish National Breast Screening Programme and Department of Histopathology, St. Vincent's University Hospital, Dublin, Ireland
| | - Michael Toss
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; Department of Histopathology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
| | - Mansour Alsaleem
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; Unit of Scientific Research, Applied College, Qassim University, Saudi Arabia
| | - Nehal M Atallah
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Asmaa Ibrahim
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | - Catrin S Rutland
- School of Veterinary Medicine and Sciences, University of Nottingham, Sutton Bonington, UK
| | - Nigel P Mongan
- Biodiscovery Institute, School of Veterinary Medicine and Sciences, University of Nottingham, Nottingham, UK; Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA
| | - Emad A Rakha
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, UK; Department of Pathology, Hamad Medical Corporation, Doha, Qatar.
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Curigliano G, Burstein HJ, Gnant M, Loibl S, Cameron D, Regan MM, Denkert C, Poortmans P, Weber WP, Thürlimann B. Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023. Ann Oncol 2023; 34:970-986. [PMID: 37683978 DOI: 10.1016/j.annonc.2023.08.017] [Citation(s) in RCA: 91] [Impact Index Per Article: 45.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
The 18th St Gallen International Breast Cancer Conference held in March 2023, in Vienna, Austria, assessed significant new findings for local and systemic therapies for early breast cancer with a focus on the evaluation of multimodal treatment options. The emergence of more effective, innovative agents in both the preoperative (primary or neoadjuvant) and post-operative (adjuvant) settings has underscored the pivotal role of a multidisciplinary approach in treatment decision making, particularly when selecting systemic therapy for an individual patient. The importance of multidisciplinary discussions regarding the clinical benefits of interventions was explicitly emphasized by the consensus panel as an integral part of developing an optimal treatment plan with the 'right' degree of intensity and duration. The panelists focused on controversies surrounding the management of common ductal/no special type and lobular breast cancer histology, which account for the vast majority of breast tumors. The expert opinion of the panelists was based on interpretations of available data, as well as current practices in their professional environments, personal and socioeconomic factors affecting patients, and cognizant of varying reimbursement and accessibility constraints around the world. The panelists strongly advocated patient participation in well-designed clinical studies whenever feasible. With these considerations in mind, the St Gallen Consensus Conference aims to offer guidance to clinicians regarding appropriate treatments for early-stage breast cancer and assist in balancing the realistic trade-offs between treatment benefit and toxicity, enabling patients and clinicians to make well-informed choices through a shared decision-making process.
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Affiliation(s)
- G Curigliano
- Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
| | - H J Burstein
- Medical Oncology, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston, USA.
| | - M Gnant
- Comprehensive Cancer Center, Medical University of Vienna, Vienna; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria
| | - S Loibl
- Center for Hematology and Oncology Bethanien, Frankfurt; German Breast Group, Neu-Isenburg, Germany
| | - D Cameron
- Edinburgh Cancer Research Centre, University of Edinburgh and NHS Lothian, Edinburgh, UK
| | - M M Regan
- International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - C Denkert
- Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum Marburg, Marburg, Germany
| | - P Poortmans
- Department of Radiation Oncology, Iridium Netwerk, Wilrijk-Antwerp; University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium
| | - W P Weber
- Department of Surgery, University Hospital Basel, Basel, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland
| | - B Thürlimann
- SwissBreastCare, Bethanienspital, Zürich, Switzerland; SONK Foundation, St. Gallen, Switzerland
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12
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Moldoveanu D, Hoskin TL, Day CN, Schulze AK, Goetz MP, Boughey JC. Clinical Behavior, Management, and Treatment Response of Estrogen Receptor Low (1-10%) Breast Cancer. Ann Surg Oncol 2023; 30:6475-6483. [PMID: 37460743 DOI: 10.1245/s10434-023-13846-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 06/19/2023] [Indexed: 09/20/2023]
Abstract
INTRODUCTION Estrogen receptor (ER) and progesterone receptor (PR) guide management and impact outcomes of breast cancer (BC). This study compares ER-low (1-10%) with ER-negative (< 1%) and ER-positive (>10%) BC and investigates the significance of PR expression within ER-low disease. PATIENTS AND METHODS All patients with HER2-negative invasive BC were identified from the National Cancer Database 2018-2019. Treatment and outcomes were compared using chi-squared tests and multivariable logistic regression. RESULTS Of 232,762 patients, ER expression was: negative (13.8%), low (2.0%), and > 10% (84.2%). Chemotherapy was given in 83.9% of ER- disease, 82.4% of ER-low/PR- disease, 58.9% of ER-low/PR+ disease, and only in 22.9% of ER+ disease. Within the ER-low subgroup, adjuvant endocrine therapy, recurrence score, and Ki67 varied by PR status (all < 0.01). Patients with ER-low disease selected for neoadjuvant chemotherapy (NAC) were younger and had higher T and N category, tumor grade, and Ki67. With NAC, pathological complete response (pCR) rates were similar between ER-low/PR- and ER-low/PR+ (39.5% and 38.1%, respectively, p = 0.67), and were closer to the ER- group (39.7%) than the ER+ group (8.4%). On multivariable analysis, the adjusted effect of ER status (1-10% versus > 10%) on chemotherapy administration was odds ratio (OR) 8.2 (95% CI 7.3-9.2, p < 0.001) for PR-negative, and OR 3.3 (95% CI 7.3-9.2, p < 0.001) for PR-positive. CONCLUSIONS This study suggests that the tumor features and clinical management of ER-low tumors vary significantly by PR expression. Within ER-low tumors, PR- tumors more closely resemble ER- BC, while PR+ tumors exhibit less aggressive characteristics. In ER-low disease selected for treatment with NAC, response is similar to ER- regardless of PR status.
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Affiliation(s)
- Dan Moldoveanu
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Tanya L Hoskin
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Courtney N Day
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Amy K Schulze
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Judy C Boughey
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
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13
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Makhlouf S, Althobiti M, Toss M, Muftah AA, Mongan NP, Lee AHS, Green AR, Rakha EA. The Clinical and Biological Significance of Estrogen Receptor-Low Positive Breast Cancer. Mod Pathol 2023; 36:100284. [PMID: 37474005 DOI: 10.1016/j.modpat.2023.100284] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 06/05/2023] [Accepted: 07/13/2023] [Indexed: 07/22/2023]
Abstract
Estrogen receptor (ER) status in breast cancer (BC) is determined using immunohistochemistry (IHC) with nuclear expression in ≥1% of cells defined as ER-positive. BC with 1%-9% expression (ER-low-positive), is a clinically and biologically unique subgroup. In this study, we hypothesized that ER-low-positive BC represents a heterogeneous group with a mixture of ER-positive and ER-negative tumor, which may explain their divergent clinical behavior. A large BC cohort (n = 8171) was investigated and categorized into 3 groups: ER-low-positive (1%-9%), ER-positive (≥10%), and ER-negative (<1%) where clinicopathological and outcome characteristics were compared. A subset of ER-low-positive cases was further evaluated using IHC, RNAscope, and RT-qPCR. PAM50 subtyping and ESR1 mRNA expression levels were assessed in ER-low-positive cases within The Cancer Genome Atlas data set. The reliability of image analysis software in assessment of ER expression in the ER-low-positive category was also assessed. ER-low-positive tumors constituted <2% of BC cases examined and showed significant clinicopathological similarity to ER-negative tumors. Most of these tumors were nonluminal types showing low ESR1 mRNA expression. Further validation of ER status revealed that 45% of these tumors were ER-negative with repeated IHC staining and confirmed by RNAscope and RT-qPCR. ER-low-positive tumors diagnosed on needle core biopsy were enriched with false-positive ER staining. BCs with 10% ER behaved similar to ER-positive, rather than ER-negative or low-positive BCs. Moderate concordance was found in assessment of ER-low-positive tumors, and this was not improved by image analysis. Routinely diagnosed ER-low-positive BC includes a proportion of ER-negative cases. We recommend repeat testing of BC showing 1%-9% ER expression and using a cutoff ≥10% expression to define ER positivity to help better inform treatment decisions.
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Affiliation(s)
- Shorouk Makhlouf
- Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Maryam Althobiti
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia
| | - Michael Toss
- Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Histopathology, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom
| | - Abir A Muftah
- Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya
| | - Nigel P Mongan
- Biodiscovery Institute, School of Veterinary Medicine and Sciences, University of Nottingham, Nottingham, United Kingdom; Department of Pharmacology, Weill Cornell Medicine, New York, New York
| | - Andrew H S Lee
- Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | - Andrew R Green
- Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Emad A Rakha
- Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; Department of Pathology, Hamad Medical Corporation, Doha, Qatar.
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14
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Wei S. Hormone receptors in breast cancer: An update on the uncommon subtypes. Pathol Res Pract 2023; 250:154791. [PMID: 37672851 DOI: 10.1016/j.prp.2023.154791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 08/21/2023] [Accepted: 09/01/2023] [Indexed: 09/08/2023]
Abstract
Breast cancer is the most common cancer affecting women and is the second leading cause of cancer death among US women. Estrogen receptor (ER) signaling plays a crucial role in mammary gland development and carcinogenesis. Near 80 % of invasive breast cancers are ER-positive (ER+). Endocrine therapies targeting ER have significantly improved the prognostic outcomes in the patients with ER+ breast cancer, and the therapeutic effects are strongly correlated with the levels of the ER expression in tumor cells. Despite being an ER-dependent gene product, PR is not always overexpressed in ER+ tumors, and a small subset of breast cancers demonstrates an ER+/PR- phenotype, and a rare ER-/PR+ subtype also exists. There have been controversies on the biology of these tumor types and the predictive and prognostic power of PR status. Compelling data have shown the distinct biologic characteristics of ER+/PR- and ER-/PR+ tumors. Despite that ER-low breast cancers demonstrate more similarity to ER- tumors, at least a subset of ER-low carcinomas may have a functional ER signaling. Thus, adequate PR expression is essential as its absence indicates impaired ER pathway. Assessment of PR status may not only distinguish the ER+/PR- subset from the ER+ and ER-low tumors, but also differentiate the ER-/PR+ phenotype from the ER- carcinomas, both with therapeutic implications. This article was aimed to provide an up-to-date review focusing on the clinicopathologic characteristics of uncommon subtypes of breast cancer, including ER+/PR-, ER-/PR+, and ER-low breast cancers.
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Affiliation(s)
- Shi Wei
- Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, 4000 Cambridge Street, Kansas City, KS 66160, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35249, United States.
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15
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Chen HL, Huang FB, Chen Q, Deng YC. Impact of estrogen receptor expression level on response to neoadjuvant chemotherapy and prognosis in HER2-negative breast cancers. BMC Cancer 2023; 23:841. [PMID: 37684569 PMCID: PMC10485958 DOI: 10.1186/s12885-023-11368-2] [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: 11/16/2022] [Accepted: 09/04/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND Breast cancers with 1-10% cell staining for estrogen receptor (ER) present particular clinical features. The clinical data of estrogen receptor expression level and treatment effect are limited, particularly regarding chemotherapy benefit. We evaluated the pathologic response to neoadjuvant chemotherapy (NAC) in ER low positive tumors (ER staining 1-10%) and compared it with ER > 10% positive tumors (ER staining > 10%) and ER-negative tumors. We further explored the differences in recurrence and survival with respect to the ER expression level. METHOD Patients with stages II and III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery were categorized according to their ER percentages into three groups: ER-negative, ER low positive, and ER > 10% positive. Logistic regression models were used to assess the association between each variable and pathologic complete response (pCR). Kaplan‒Meier analysis was used to estimate survival outcomes. Cox models were used to adjust for patient and tumor characteristics. RESULTS A total of 241 patients were analyzed. Of all patients included, 22 (9.1%) had ER low positive tumors, 159 (66.0%) had ER > 10% positive tumors, and 60 (24.9%) were ER-negative. Low ER positivity was significantly associated with a higher pCR rate than ER > 10% positivity (OR, 0.249; 95% CI, 0.067-0.923; P = 0.038). After a median follow-up time of 32 months, the disease-free survival (DFS) and overall survival (OS) of the patients with ER low positive tumors were significantly worse than those of the patients with ER > 10% positive tumors but similar to those with ER-negative tumors. After adjustment for covariates, ER low positive tumors were significantly associated with worse DFS than ER > 10% positive tumors. CONCLUSION Our results indicated that ER low positive breast cancer presents a better response to neoadjuvant chemotherapy and significantly worse prognosis for patients than those with ER > 10% positive tumors, but similar to the ER-negative group. These data support that this category of patients behaves clinically like patients with ER-negative breast cancer and should be treated differently from patients with ER > 10% positive tumors. Further prospective study is needed.
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Affiliation(s)
- Hai-Long Chen
- Department of Breast Surgery, the Second Affiliated Hospital of Zhejiang, University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Feng-Bo Huang
- Department of Pathology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Qiang Chen
- Department of Breast Surgery, the Second Affiliated Hospital of Zhejiang, University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yong-Chuan Deng
- Department of Breast Surgery, the Second Affiliated Hospital of Zhejiang, University School of Medicine, Hangzhou, Zhejiang Province, China.
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16
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Liu Y, Han D, Parwani AV, Li Z. Applications of Artificial Intelligence in Breast Pathology. Arch Pathol Lab Med 2023; 147:1003-1013. [PMID: 36800539 DOI: 10.5858/arpa.2022-0457-ra] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/15/2022] [Indexed: 02/19/2023]
Abstract
CONTEXT.— Increasing implementation of whole slide imaging together with digital workflow and advances in computing capacity enable the use of artificial intelligence (AI) in pathology, including breast pathology. Breast pathologists often face a significant workload, with diagnosis complexity, tedious repetitive tasks, and semiquantitative evaluation of biomarkers. Recent advances in developing AI algorithms have provided promising approaches to meet the demand in breast pathology. OBJECTIVE.— To provide an updated review of AI in breast pathology. We examined the success and challenges of current and potential AI applications in diagnosing and grading breast carcinomas and other pathologic changes, detecting lymph node metastasis, quantifying breast cancer biomarkers, predicting prognosis and therapy response, and predicting potential molecular changes. DATA SOURCES.— We obtained data and information by searching and reviewing literature on AI in breast pathology from PubMed and based our own experience. CONCLUSIONS.— With the increasing application in breast pathology, AI not only assists in pathology diagnosis to improve accuracy and reduce pathologists' workload, but also provides new information in predicting prognosis and therapy response.
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Affiliation(s)
- Yueping Liu
- From the Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China (Liu, Han)
| | - Dandan Han
- From the Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China (Liu, Han)
| | - Anil V Parwani
- The Department of Pathology, The Ohio State University, Columbus (Parwani, Li)
| | - Zaibo Li
- From the Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China (Liu, Han)
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17
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Zhu Z, Jiang L, Ding X. Advancing Breast Cancer Heterogeneity Analysis: Insights from Genomics, Transcriptomics and Proteomics at Bulk and Single-Cell Levels. Cancers (Basel) 2023; 15:4164. [PMID: 37627192 PMCID: PMC10452610 DOI: 10.3390/cancers15164164] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/23/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Breast cancer continues to pose a significant healthcare challenge worldwide for its inherent molecular heterogeneity. This review offers an in-depth assessment of the molecular profiling undertaken to understand this heterogeneity, focusing on multi-omics strategies applied both in traditional bulk and single-cell levels. Genomic investigations have profoundly informed our comprehension of breast cancer, enabling its categorization into six intrinsic molecular subtypes. Beyond genomics, transcriptomics has rendered deeper insights into the gene expression landscape of breast cancer cells. It has also facilitated the formulation of more precise predictive and prognostic models, thereby enriching the field of personalized medicine in breast cancer. The comparison between traditional and single-cell transcriptomics has identified unique gene expression patterns and facilitated the understanding of cell-to-cell variability. Proteomics provides further insights into breast cancer subtypes by illuminating intricate protein expression patterns and their post-translational modifications. The adoption of single-cell proteomics has been instrumental in this regard, revealing the complex dynamics of protein regulation and interaction. Despite these advancements, this review underscores the need for a holistic integration of multiple 'omics' strategies to fully decipher breast cancer heterogeneity. Such integration not only ensures a comprehensive understanding of breast cancer's molecular complexities, but also promotes the development of personalized treatment strategies.
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Affiliation(s)
- Zijian Zhu
- State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China;
| | - Lai Jiang
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200025, China;
| | - Xianting Ding
- State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China;
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200025, China;
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18
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Fan Y, Zhong X, Wang Y, Wang Z, Luo T, Wang Y, Zheng H. A prospective cohort study of clinical characteristics and outcomes in Chinese patients with estrogen receptor-negative/progesterone receptor-positive early breast cancer. Breast Cancer Res Treat 2023:10.1007/s10549-023-06964-6. [PMID: 37199804 DOI: 10.1007/s10549-023-06964-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/19/2023] [Indexed: 05/19/2023]
Abstract
PURPOSE This study aimed to examine the clinical characteristics and outcomes of patients with estrogen receptor-negative (ER-)/progesterone receptor-positive (PR+) early breast cancer. We also aimed to investigate the benefits of adjuvant endocrine therapy (ET) in this patient population. METHODS Patients with early breast cancer diagnosed at West China Hospital were divided into the ER-/PR+, ER+, and ER-/PR- groups. The chi-square test was used to analyze differences in clinical and pathological features among the groups. Multivariable Cox and Fine-Gray regression models were used to compare mortality and locoregional recurrence (LRR)/distant recurrence (DR), respectively. We performed a subgroup analysis to determine which ER-/PR+ patients can benefit more from ET. RESULTS From 2008 to 2020, we enrolled 443, 7104, and 2892 patients into the ER-/PR+, ER+, and ER-/PR- groups, respectively. The ER-/PR+ group showed more unfavorable clinical features and aggressive pathological characteristics than the ER+ group. The mortality, LRR, and DR rates were higher in the ER-/PR+ than in the ER+ group. Most clinical features and pathological characteristics were similar between the ER-/PR+ and ER-/PR- group and their outcomes were comparable. In the ER-/PR+ group, patients who received ET showed significantly lower LRR and mortality rates than those who did not; however, no difference was observed in DR. Subgroup analysis suggested that ER-/PR+ patients age ≥ 55 years, and postmenopausal status can benefit from ET. CONCLUSION ER-/PR+ tumors have more aggressive pathological characteristics and more unfavorable clinical features than ER+ tumors. ET can reduce the LRR and mortality rates in ER-/PR+ patients. Postmenopausal and age ≥ 55 years ER-/PR+ patients can benefit from ET.
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Affiliation(s)
- Yu Fan
- Breast Center and Multi-omics Laboratory of Breast Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xiaorong Zhong
- Breast Center and Multi-omics Laboratory of Breast Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Yu Wang
- Breast Center and Multi-omics Laboratory of Breast Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Zhu Wang
- Breast Center and Multi-omics Laboratory of Breast Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Ting Luo
- Breast Center and Multi-omics Laboratory of Breast Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Yanping Wang
- Breast Center and Multi-omics Laboratory of Breast Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
| | - Hong Zheng
- Breast Center and Multi-omics Laboratory of Breast Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
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19
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Elayoubi J, Chi J, Mahmoud AA, Alloghbi A, Assad H, Shekhar M, Simon MS. A Review of Endocrine Therapy in Early-stage Breast Cancer: The Journey From Crudeness to Precision. Am J Clin Oncol 2023; 46:225-230. [PMID: 36856249 DOI: 10.1097/coc.0000000000000993] [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: 03/02/2023]
Abstract
Endocrine therapy (ET) is the standard of care for hormone receptor-positive early-stage breast cancer in the adjuvant setting. However, response to ET can vary across patient subgroups. Historically, hormone receptor expression and clinical stage are the main predictors of the benefit of ET. A "window of opportunity" trials has raised significant interest in recent years as a means of assessing the sensitivity of a patient's cancer to short-term neoadjuvant ET, which provides important prognostic information, and helps in decision-making regarding treatment options in a time-efficient and cost-efficient manner. In the era of genomics, molecular profiling has led to the discovery and evaluation of the prognostic and predictive abilities of new molecular profiles. To realize the goal of personalized medicine, we are in urgent need to explore reliable biomarkers or genomic signatures to accurately predict the clinical response and long-term outcomes associated with ET. Validation of these biomarkers as reliable surrogate endpoints can also lead to a revolution in the clinical trial designs, and potentially avoid the need for repeated tissue biopsies in the surveillance of disease response. The clinical potential of tumor genomic profiling marks the beginning of a new era of precision medicine in breast cancer treatment.
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Affiliation(s)
- Jailan Elayoubi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI
| | - Jie Chi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI
| | - Amr A Mahmoud
- Department of Clinical Oncology, Kafr Elshiekh University, Egypt
| | - Abdurahman Alloghbi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI
| | - Hadeel Assad
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI
| | - Malathy Shekhar
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI
| | - Michael S Simon
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI
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20
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Lashen AG, Toss MS, Mongan NP, Green AR, Rakha EA. The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up. Cancer 2023; 129:1183-1194. [PMID: 36653923 DOI: 10.1002/cncr.34655] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/23/2022] [Accepted: 12/28/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND The routine assessment of progesterone receptor (PR) expression in breast cancer (BC) remains controversial. This study aimed to evaluate the role of PR expression in luminal BC, with emphasis on the definition of positivity and its prognostic significance as compared to Ki67 expression. METHODS A large cohort (n = 1924) of estrogen receptor (ER)-positive/HER2-negative BC was included. PR was immunohistochemically (IHC) stained on full face sections and core needle biopsies (CNB) where the optimal scoring cutoff was evaluated. In addition, the association of PR with other clinicopathological factors, cellular proliferation, disease outcome, and response to adjuvant therapy were analyzed. RESULTS Although several cutoffs showed prognostic significance, the optimal cutoff to categorize PR expression into two clinically distinct prognostic groups on CNB was 10%. PR negativity showed a significant association with features of aggressive tumor behavior and poor outcome. Multivariate analyses indicated that the association between PR negativity and poor outcome was independent of tumor grade, size, node stage, and Ki67. PR negativity showed independent association with shorter survival in patients who received endocrine therapy whereas Ki67did not. CONCLUSION PR IHC expression provides independent prognostic value superior to Ki67. Routine assessment of PR expression in BC using 10% cutoff in the clinical setting is recommended. PLAIN LANGUAGE SUMMARY In this study, we have established an optimal approach to determine the prognostic value of progesterone receptor expression in estrogen receptor-positive breast cancer patients. To do this, the levels of progesterone receptor were measured in a large cohort of estrogen receptor-positive breast cancer patients. We have refined the definition of progesterone receptor positivity in estrogen receptor-positive breast cancer. We show that progesterone receptor expression adds prognostic and predictive value of endocrine therapy in estrogen receptor-positive breast cancer patients, and our results show that the absence of progesterone receptor is associated with poorer outcomes independent of tumor grade, size, node stage, and Ki67 expression.
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Affiliation(s)
- Ayat G Lashen
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt
| | - Michael S Toss
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Histopathology, Sheffield Teaching Hospitals Foundation NHS Trust, Sheffield, UK
| | - Nigel P Mongan
- School of Veterinary Medicine and Sciences, University of Nottingham, Nottingham, UK
- Department of Pharmacology, Weill Cornell Medicine, New York, New York, USA
| | - Andrew R Green
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
- Nottingham Breast Cancer Research Centre, University of Nottingham, Nottingham, UK
| | - Emad A Rakha
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt
- Department of Pathology, Hamad Medical Corporation, Doha, Qatar
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21
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Sgroi DC, Treuner K, Zhang Y, Piper T, Salunga R, Ahmed I, Doos L, Thornber S, Taylor KJ, Brachtel E, Pirrie S, Schnabel CA, Rea D, Bartlett JMS. Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study. Breast Cancer Res 2022; 24:90. [PMID: 36527133 PMCID: PMC9758861 DOI: 10.1186/s13058-022-01589-x] [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: 08/24/2022] [Accepted: 12/07/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. METHODS Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson's correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. RESULTS EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = - 0.18), PR (r = - 0.25), and AR (r = - 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). CONCLUSION These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.
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Affiliation(s)
- Dennis C Sgroi
- Molecular Pathology Research Unit, Department of Pathology, Harvard Medical School, Massachusetts General Hospital East, 149 13th Street, Charlestown, MA, 02129, USA.
- Massachusetts General Hospital Center for Cancer Research, Harvard Medical School, Boston, MA, USA.
| | - Kai Treuner
- Biotheranostics, A Hologic Company, San Diego, CA, USA
| | - Yi Zhang
- Biotheranostics, A Hologic Company, San Diego, CA, USA
| | | | | | - Ikhlaaq Ahmed
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Lucy Doos
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Sarah Thornber
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | | | - Elena Brachtel
- Molecular Pathology Research Unit, Department of Pathology, Harvard Medical School, Massachusetts General Hospital East, 149 13th Street, Charlestown, MA, 02129, USA
- Massachusetts General Hospital Center for Cancer Research, Harvard Medical School, Boston, MA, USA
| | - Sarah Pirrie
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | | | - Daniel Rea
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - John M S Bartlett
- University of Edinburgh, Edinburgh, UK
- Ontario Institute for Cancer Research, Ontario, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
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22
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Woeste MR, Jacob K, Duff MB, Donaldson M, Sanders MAG, McMasters KM, Ajkay N. Impact of routine expert breast pathology consultation and factors predicting discordant diagnosis. Surg Oncol 2022; 45:101860. [DOI: 10.1016/j.suronc.2022.101860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 09/10/2022] [Accepted: 10/02/2022] [Indexed: 12/05/2022]
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23
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Gown AM. Commentary on "Application of Photoshop-based Image Analysis to Quantification of Hormone Receptor Expression in Breast Cancer". J Histochem Cytochem 2022; 70:767-768. [PMID: 36546603 PMCID: PMC9903209 DOI: 10.1369/00221554221145227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
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24
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Stettler S, Aebi S. [Endocrine Treatments in Breast Cancer]. PRAXIS 2022; 111:550-556. [PMID: 35920011 DOI: 10.1024/1661-8157/a003878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Endocrine Treatments in Breast Cancer Abstract. Breast cancer, the most common cancer in women, expresses estrogen and/or progesterone receptors in about 75% of patients. This allows for the use of endocrine treatments. Adjuvant therapy with tamoxifen for 5 years reduces the mortality by about 33%; the residual risk can be lowered by using aromatase inhibitors and by prolonging the treatment. In patients with advanced disease, the median duration of response to first-line therapy is about twelve months, and the median survival time is 20 to 40 months. The use of the various substances differs in terms of duration, sequence, and combinations, particularly with CDK4/6-inhibitors, depending on the clinical situation. Endocrine therapies are prescribed over a long period of time. Treatment adherence is improved by optimal control of side effects.
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Affiliation(s)
- Sonja Stettler
- Tumorzentrum LUKS, Medizinische Onkologie, Luzerner Kantonsspital, Luzern, Schweiz
| | - Stefan Aebi
- Tumorzentrum LUKS, Medizinische Onkologie, Luzerner Kantonsspital, Luzern, Schweiz
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25
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Moroni S, Casettari L, Lamprou DA. 3D and 4D Printing in the Fight against Breast Cancer. BIOSENSORS 2022; 12:568. [PMID: 35892465 PMCID: PMC9394292 DOI: 10.3390/bios12080568] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/22/2022] [Accepted: 07/25/2022] [Indexed: 06/15/2023]
Abstract
Breast cancer is the second most common cancer worldwide, characterized by a high incidence and mortality rate. Despite the advances achieved in cancer management, improvements in the quality of life of breast cancer survivors are urgent. Moreover, considering the heterogeneity that characterizes tumors and patients, focusing on individuality is fundamental. In this context, 3D printing (3DP) and 4D printing (4DP) techniques allow for a patient-centered approach. At present, 3DP applications against breast cancer are focused on three main aspects: treatment, tissue regeneration, and recovery of the physical appearance. Scaffolds, drug-loaded implants, and prosthetics have been successfully manufactured; however, some challenges must be overcome to shift to clinical practice. The introduction of the fourth dimension has led to an increase in the degree of complexity and customization possibilities. However, 4DP is still in the early stages; thus, research is needed to prove its feasibility in healthcare applications. This review article provides an overview of current approaches for breast cancer management, including standard treatments and breast reconstruction strategies. The benefits and limitations of 3DP and 4DP technologies are discussed, as well as their application in the fight against breast cancer. Future perspectives and challenges are outlined to encourage and promote AM technologies in real-world practice.
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Affiliation(s)
- Sofia Moroni
- School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UK;
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy;
| | - Luca Casettari
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy;
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26
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Ramin C, Gierach GL, Abubakar M, Veiga LHS, Vo JB, Curtis RE, Bowles EJA, Feigelson HS, Buist DSM, Berrington de Gonzalez A, Bodelon C. The influence of treatment on hormone receptor subgroups and breast cancer-specific mortality within US integrated healthcare systems. Cancer Causes Control 2022; 33:1019-1023. [PMID: 35583697 PMCID: PMC9701354 DOI: 10.1007/s10552-022-01589-4] [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: 10/28/2021] [Accepted: 05/02/2022] [Indexed: 11/12/2022]
Abstract
PURPOSE Estrogen receptor (ER) + /progesterone receptor (PR) - or ER-/PR + breast cancer prognosis has not been well-described outside of clinical trials. We evaluated the relationship between ER/PR (ER + /PR-, ER-/PR + , ER + /PR + , ER-/PR-) subgroups and breast cancer-specific mortality within a general community setting in the US. METHODS A Retrospective cohort of 11,737 women diagnosed with breast cancer between 1990 and 2016 within US integrated healthcare systems (median follow-up = 7 years; 1,104 breast cancer-specific deaths) were included in this analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for site, demographic and clinicopathological characteristics, and treatment (surgery/radiotherapy, chemotherapy, endocrine therapy). RESULTS Breast cancer-specific mortality was higher for those with ER + /PR- (n = 1,233) compared with ER + /PR + tumors (n = 8,439) before (HR = 1.43; 95% CI = 1.17-1.75) and after treatment adjustment (HR = 1.58; 95% CI = 1.27-1.97). ER + /PR- breast cancer-specific mortality remained higher than ER + /PR + tumors when stratified by treatment received. Breast cancer-specific mortality was similar in ER-/PR + (n = 161) compared with ER + /PR + tumors. CONCLUSION Our findings suggest that ER + /PR- tumors may have worse breast cancer-specific mortality than ER + /PR + tumors in a community setting.
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Affiliation(s)
- Cody Ramin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA
| | - Gretchen L Gierach
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA
| | - Mustapha Abubakar
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA
| | - Lene H S Veiga
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA
| | - Jacqueline B Vo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA
| | - Rochelle E Curtis
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA
| | - Erin J Aiello Bowles
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA
| | - Heather Spencer Feigelson
- Bernard J. Tyson Kaiser Permanente School of Medicine, Pasadena, CA, USA
- Institute for Health Research, Kaiser Permanente, Denver, CO, USA
| | - Diana S M Buist
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA
- Bernard J. Tyson Kaiser Permanente School of Medicine, Pasadena, CA, USA
| | - Amy Berrington de Gonzalez
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA
| | - Clara Bodelon
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 9609 Medical Center Drive, Bethesda, MD, USA.
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27
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Fei F, Siegal GP, Wei S. Characterizing Clinicopathologic Features of Estrogen Receptor-Positive/Progesterone Receptor-Negative Breast Cancers. Clin Breast Cancer 2022; 22:e788-e797. [DOI: 10.1016/j.clbc.2022.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 06/14/2022] [Accepted: 07/01/2022] [Indexed: 11/26/2022]
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28
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Hou Y, Peng Y, Li Z. Update on prognostic and predictive biomarkers of breast cancer. Semin Diagn Pathol 2022; 39:322-332. [PMID: 35752515 DOI: 10.1053/j.semdp.2022.06.015] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 06/10/2022] [Accepted: 06/15/2022] [Indexed: 11/11/2022]
Abstract
Breast cancer represents a heterogeneous group of human cancer at both histological and molecular levels. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are the most commonly used biomarkers in clinical practice for making treatment plans for breast cancer patients by oncologists. Recently, PD-L1 testing plays an important role for immunotherapy for triple-negative breast cancer. With the increased understanding of the molecular characterization of breast cancer and the emergence of novel targeted therapies, more potential biomarkers are needed for the development of more personalized treatments. In this review, we summarized several main prognostic and predictive biomarkers in breast cancer at genomic, transcriptomic and proteomic levels, including hormone receptors, HER2, Ki67, multiple gene expression assays, PD-L1 testing, mismatch repair deficiency/microsatellite instability, tumor mutational burden, PIK3CA, ESR1 andNTRK and briefly introduced the roles of digital imaging analysis in breast biomarker evaluation.
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Affiliation(s)
- Yanjun Hou
- Department of Pathology, Atrium Health Wake Forest Baptist Medical Center, Winston Salem, NC
| | - Yan Peng
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX
| | - Zaibo Li
- Department of pathology, The Ohio State University Wexner Medical Center, Columbus OH.
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29
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Krishnamurthy K, Deb A, Alghamdi S, Schwartz M, Cusnir M, Sriganeshan V, Poppiti R. ROS1 altered breast cancers - a distinctive molecular subtype of PR- metastatic breast cancers: Expanding the scope of targeted therapeutics. Breast Dis 2022; 41:295-301. [PMID: 35634843 DOI: 10.3233/bd-220001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Breast cancer, one of the leading causes of cancer-related mortality in women worldwide, exhibits wide-ranging histo-morphologic, clinical and molecular diversity. OBJECTIVE This study compares the genetic alterations of breast tumors with the histo-morphological, hormone receptor status and metastatic "organotropism". MATERIALS AND METHODS Twenty-two cases of primary invasive breast carcinoma with local/distant metastasis were retrieved from the pathology archives. The status of estrogen and progesterone receptors by immunohistochemistry was recorded along with other pertinent case data. Next generation sequencing was performed on formalin-fixed paraffin embedded blocks of tumor. RESULTS The mean age of the study subjects was 57.9 ± 13.3 years. TP53 mutation was the most common gene alteration in this study and was seen in 40.9% cases. ROS1 gene was mutated in 44.4% PR negative breast cancers while being wild type in the twelve PR positive tumors. (p = 0.021).STRING interaction network constructed with ROS1 and PR revealed a significantly higher number of interactions in this network than expected (p-value 0.000973). CONCLUSION This study highlights the significantly higher incidence of ROS1 gene alterations in metastatic PR- breast cancers, with STRING network analysis revealing higher nodal interaction in the nodal network comprised of PR and ROS1 exclusive of ER.
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Affiliation(s)
- Kritika Krishnamurthy
- A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA
| | - Arunima Deb
- A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA
| | - Sarah Alghamdi
- A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA.,Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Michael Schwartz
- Department of Medical Oncology, Mount Sinai Medical Center, Miami Beach, FL, USA
| | - Mike Cusnir
- Department of Medical Oncology, Mount Sinai Medical Center, Miami Beach, FL, USA
| | - Vathany Sriganeshan
- A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA.,Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Robert Poppiti
- A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA.,Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
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30
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Miglietta F, Griguolo G, Bottosso M, Giarratano T, Lo Mele M, Fassan M, Cacciatore M, Genovesi E, De Bartolo D, Vernaci G, Amato O, Porra F, Conte P, Guarneri V, Dieci MV. HER2-low-positive breast cancer: evolution from primary tumor to residual disease after neoadjuvant treatment. NPJ Breast Cancer 2022; 8:66. [PMID: 35595761 PMCID: PMC9122970 DOI: 10.1038/s41523-022-00434-w] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 04/14/2022] [Indexed: 11/09/2022] Open
Abstract
Approximately a half of breast tumors classified as HER2-negative exhibit HER2-low-positive expression. We recently described a high instability of HER2-low-positive expression from primary breast cancer (BC) to relapse. Previous studies reporting discordance in HER2 status between baseline biopsy and residual disease (RD) in patients undergoing neoadjuvant treatment did not include the HER2-low-positive category. The aim of this study is to track the evolution of HER2-low-positive expression from primary BC to RD after neoadjuvant treatment. Patients undergoing neoadjuvant treatment with available baseline tumor tissue and matched samples of RD (in case of no pCR) were included. HER2-negative cases were sub-classified as HER2-0 or HER2-low-positive (IHC 1+ or 2+ and ISH negative). Four-hundred forty-six patients were included. Primary BC phenotype was: HR-positive/HER2-negative 23.5%, triple-negative (TN) 35%, HER2-positive 41.5%. HER2-low-positive cases were 55.6% of the HER2-negative cohort and were significantly enriched in the HR-positive/HER2-negative vs. TN subgroup (68.6% vs. 46.8%, p = 0.001 χ2 test). In all, 35.3% of non-pCR patients (n = 291) had a HER2-low-positive expression on RD. The overall rate of HER2 expression discordance was 26.4%, mostly driven by HER2-negative cases converting either from (14.8%) or to (8.9%) HER2-low-positive phenotype. Among HR-positive/HER2-negative patients with HER2-low-positive expression on RD, 32.0% and 57.1% had an estimated high risk of relapse according to the residual proliferative cancer burden and CPS-EG score, respectively. In conclusion, HER2-low-positive expression showed high instability from primary BC to RD after neoadjuvant treatment. HER2-low-positive expression on RD may guide personalized adjuvant treatment for high-risk patients in the context of clinical trials with novel anti-HER2 antibody-drug conjugates.
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Affiliation(s)
- Federica Miglietta
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Gaia Griguolo
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Michele Bottosso
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Tommaso Giarratano
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Marcello Lo Mele
- Surgical Pathology Unit, University Hospital of Padua, 35121, Padua, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, 35121, Padua, Italy
- Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy
| | - Matilde Cacciatore
- Department of Pathology and Molecular Genetics, Treviso General Hospital, Treviso, Italy
| | - Elisa Genovesi
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Debora De Bartolo
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, 35121, Padua, Italy
| | - Grazia Vernaci
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Ottavia Amato
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Francesca Porra
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - PierFranco Conte
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
| | - Valentina Guarneri
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy.
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy.
| | - Maria Vittoria Dieci
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy
- Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy
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31
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Balma M, Liberini V, Racca M, Laudicella R, Bauckneht M, Buschiazzo A, Nicolotti DG, Peano S, Bianchi A, Albano G, Quartuccio N, Abgral R, Morbelli SD, D'Alessandria C, Terreno E, Huellner MW, Papaleo A, Deandreis D. Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review. Front Med (Lausanne) 2022; 9:881551. [PMID: 35492341 PMCID: PMC9039137 DOI: 10.3389/fmed.2022.881551] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 03/22/2022] [Indexed: 02/05/2023] Open
Abstract
Breast cancer is one of the most common malignancies in women, with high morbidity and mortality rates. In breast cancer, the use of novel radiopharmaceuticals in nuclear medicine can improve the accuracy of diagnosis and staging, refine surveillance strategies and accuracy in choosing personalized treatment approaches, including radioligand therapy. Nuclear medicine thus shows great promise for improving the quality of life of breast cancer patients by allowing non-invasive assessment of the diverse and complex biological processes underlying the development of breast cancer and its evolution under therapy. This review aims to describe molecular probes currently in clinical use as well as those under investigation holding great promise for personalized medicine and precision oncology in breast cancer.
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Affiliation(s)
- Michele Balma
- Nuclear Medicine Department, S. Croce e Carle Hospital, Cuneo, Italy
| | - Virginia Liberini
- Nuclear Medicine Department, S. Croce e Carle Hospital, Cuneo, Italy
- Division of Nuclear Medicine, Department of Medical Science, University of Turin, Turin, Italy
| | - Manuela Racca
- Nuclear Medicine Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
| | - Riccardo Laudicella
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, Messina, Italy
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- Nuclear Medicine Unit, Fondazione Istituto G. Giglio, Cefalù, Italy
| | - Matteo Bauckneht
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Department of Health Science (DISSAL), University of Genoa, Genoa, Italy
| | - Ambra Buschiazzo
- Nuclear Medicine Department, S. Croce e Carle Hospital, Cuneo, Italy
| | | | - Simona Peano
- Nuclear Medicine Department, S. Croce e Carle Hospital, Cuneo, Italy
| | - Andrea Bianchi
- Nuclear Medicine Department, S. Croce e Carle Hospital, Cuneo, Italy
| | - Giovanni Albano
- Nuclear Medicine Unit, Fondazione Istituto G. Giglio, Cefalù, Italy
| | - Natale Quartuccio
- Nuclear Medicine Unit, A.R.N.A.S. Civico di Cristina and Benfratelli Hospitals, Palermo, Italy
| | - Ronan Abgral
- Department of Nuclear Medicine, University Hospital of Brest, Brest, France
| | - Silvia Daniela Morbelli
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Department of Health Science (DISSAL), University of Genoa, Genoa, Italy
| | | | - Enzo Terreno
- Department of Molecular Biotechnology and Health Sciences, Molecular & Preclinical Imaging Centers, University of Turin, Turin, Italy
| | - Martin William Huellner
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Alberto Papaleo
- Nuclear Medicine Department, S. Croce e Carle Hospital, Cuneo, Italy
| | - Désirée Deandreis
- Division of Nuclear Medicine, Department of Medical Science, University of Turin, Turin, Italy
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32
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Garutti M, Griguolo G, Botticelli A, Buzzatti G, De Angelis C, Gerratana L, Molinelli C, Adamo V, Bianchini G, Biganzoli L, Curigliano G, De Laurentiis M, Fabi A, Frassoldati A, Gennari A, Marchiò C, Perrone F, Viale G, Zamagni C, Zambelli A, Del Mastro L, De Placido S, Guarneri V, Marchetti P, Puglisi F. Definition of High-Risk Early Hormone-Positive HER2−Negative Breast Cancer: A Consensus Review. Cancers (Basel) 2022; 14:cancers14081898. [PMID: 35454806 PMCID: PMC9029479 DOI: 10.3390/cancers14081898] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/06/2022] [Accepted: 04/06/2022] [Indexed: 11/16/2022] Open
Abstract
Breast cancer is one of the major causes of cancer-related morbidity and mortality in women worldwide. During the past three decades, several improvements in the adjuvant treatment of hormone receptor-positive/HER2−negative breast cancer have been achieved with the introduction of optimized adjuvant chemotherapy and endocrine treatment. However, estimating the risk of relapse of breast cancer on an individual basis is still challenging. The IRIDE (hIGh Risk DEfinition in breast cancer) working group was established with the aim of reviewing evidence from the literature to synthesize the current relevant features that predict hormone-positive/HER2−negative early breast cancer relapse. A panel of experts in breast cancer was involved in identifying clinical, pathological, morphological, and genetic factors. A RAND consensus method was used to define the relevance of each risk factor. Among the 21 features included, 12 were considered relevant risk factors for relapse. For each of these, we provided a consensus statement and relevant comments on the supporting scientific evidence. This work may guide clinicians in the practical management of hormone-positive/HER2−negative early breast cancers.
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Affiliation(s)
- Mattia Garutti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (L.G.); (F.P.)
- Correspondence: ; Tel.: +39-04-3465-9092
| | - Gaia Griguolo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (G.G.); (V.G.)
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, 35100 Padova, Italy
| | - Andrea Botticelli
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, 00100 Rome, Italy;
| | - Giulia Buzzatti
- Department of Medical Oncology, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy; (G.B.); (C.M.); (L.D.M.)
| | - Carmine De Angelis
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80100 Naples, Italy; (C.D.A.); (S.D.P.)
| | - Lorenzo Gerratana
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (L.G.); (F.P.)
| | - Chiara Molinelli
- Department of Medical Oncology, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy; (G.B.); (C.M.); (L.D.M.)
| | - Vincenzo Adamo
- Department of Human Pathology, Papardo Hospital, University of Messina, 89121 Messina, Italy;
| | - Giampaolo Bianchini
- Department of Medical Oncology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy;
- School of Medicine and Surgery, Università Vita-Salute San Raffaele, 20020 Milan, Italy
| | - Laura Biganzoli
- Ospedale Santo Stefano, Prato Sandro Pitigliani Medical Oncology Division, Hospital of Prato, 59100 Prato, Italy;
| | - Giuseppe Curigliano
- Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20100 Milan, Italy;
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy;
| | - Michelino De Laurentiis
- Department of Breast and Thoracic Oncology, IRCCS INT Fondazione G. Pascale, 80144 Napoli, Italy;
| | - Alessandra Fabi
- Precision Medicine in Breast Cancer Unit, Department of Woman and Child Health and Public Health, IRCCS, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, 00168 Rome, Italy;
| | - Antonio Frassoldati
- Department of Traslational Medicine and for Romagna, Clinical Oncology, S Anna University Hospital, Università degli Studi di Ferrara, 44121 Ferrara, Italy;
| | - Alessandra Gennari
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy;
- Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy
| | - Caterina Marchiò
- Candiolo Cancer Institute, FPO IRCCS, 10060 Candiolo, Italy;
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Francesco Perrone
- Clinical Trials Unit, Istituto Nazionale Tumori di Napoli, IRCCS Fondazione Pascale, 80144 Naples, Italy;
| | - Giuseppe Viale
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy;
- Department of Pathology, European Institute of Oncology IRCCS, 20122 Milan, Italy
| | - Claudio Zamagni
- Medical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, 40100 Bologna, Italy;
| | - Alberto Zambelli
- Breast Cancer Section Department of Biomedical Sciences, IRCCS Humanitas Research Hospital, Humanitas University, Rozzano, 20089 Milan, Italy;
| | - Lucia Del Mastro
- Department of Medical Oncology, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy; (G.B.); (C.M.); (L.D.M.)
- Dipartimento di Medicina Interna e Specialità Mediche, University of Genova, 16159 Genova, Italy
| | - Sabino De Placido
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80100 Naples, Italy; (C.D.A.); (S.D.P.)
| | - Valentina Guarneri
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (G.G.); (V.G.)
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, 35100 Padova, Italy
| | - Paolo Marchetti
- IRCCS Istituto Dermopatico dell’Immacolata (IDI-IRCCS), 00167 Rome, Italy;
| | - Fabio Puglisi
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (L.G.); (F.P.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
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Whisnant RE. A Novel Data Analytics-derived Metric (Nearest Cluster Distance) Is Easily Implemented in Routine Practice and Correctly Identifies Breast Cancer Cases for Quality Review. J Pathol Inform 2022; 13:100005. [PMID: 35223134 PMCID: PMC8855323 DOI: 10.1016/j.jpi.2022.100005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 11/15/2021] [Indexed: 11/24/2022] Open
Abstract
Background Errors in breast cancer grading and predictive testing are clinically important and can be difficult to detect in routine practice. A quality metric able to identify a subset of breast cancer cases which are high yield on quality review would be of practical clinical benefit. Methods Data analytic techniques were used to generate consensus tumor signature centers from a dataset over 500 breast cancer cases from a single practice. Cases were assigned a novel metric, Nearest Cluster Distance, corresponding to their distances from the nearest tumor signature center. The subset of tumors exceeding a cutoff for this metric were flagged, and then reviewed and rescored in a blinded fashion together with matched controls. A simplified version of this metric was created using universally accessible methods. Results Flagged cases showed statistically significant movement toward consensus tumor signature centers compared with controls, consistent with identification of cases which could benefit from review and possible rescoring. The simplified metric performs identically. Conclusion This method can be readily applied in routine practice and is promising as a real time quality check for breast cancer diagnosis and reporting.
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Affiliation(s)
- Richard E Whisnant
- HCA Florida Healthcare, Fawcett Memorial Hospital, Department of Pathology, 21298 Olean Blvd, Port Charlotte, FL 33952, USA
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Cai Y, Shao Z, Yu K. De-escalation of five-year adjuvant endocrine therapy in patients with estrogen receptor-low positive (immunohistochemistry staining 1%-10%) breast cancer: Propensity-matched analysis from a prospectively maintained cohort. Cancer 2022; 128:1748-1756. [PMID: 35213037 PMCID: PMC9302976 DOI: 10.1002/cncr.34155] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 11/07/2021] [Accepted: 11/30/2021] [Indexed: 11/07/2022]
Abstract
BACKGROUND The standard 5 years of endocrine therapy has demonstrated additional benefits compared with short-term (2-3 years) treatment in patients with estrogen receptor (ER)-positive breast cancer; however, data specific to ER-low positive breast cancer (1%-10% by immunohistochemistry) are limited, and it is unclear whether long-term treatment is still necessary for this subgroup. METHODS The authors used the prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center for this propensity-matched analysis. The primary end point was disease-free survival. Multivariate Cox regression analysis and propensity score-matching methods were used to minimize bias. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistics were 2-sided. RESULTS From 2012 to 2017, 22,768 consecutive women had pathologically confirmed, early stage breast cancer, and 1013 (4.45%) were identified with ER-low positive disease. Among these, 634 patients met the inclusion criteria and were divided into 3 groups: those who received no endocrine therapy (n = 89), those who received 2 to 3 years of endocrine therapy (n = 185), and those who received approximately 5 years of endocrine therapy (n = 360). At a median follow-up of 65 months, there was no significant difference in disease-free survival between patients who received 2 to 3 years and 5 years of endocrine therapy (HR, 0.82; 95% CI, 0.51-1.33; P = .43). The findings were consistent after multivariate Cox analysis of the propensity score-matched samples (5 vs 2-3 years of treatment: HR, 0.74; 95% CI, 0.41-1.31; P = .30). CONCLUSIONS Short-term endocrine therapy for 2 to 3 years might be an alternative for patients who have ER-low positive breast cancer instead of the standard 5 years of treatment.
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Affiliation(s)
- Yu‐Wen Cai
- Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Shanghai Medical CollegeFudan UniversityShanghaiChina
| | - Zhi‐Ming Shao
- Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Shanghai Key Laboratory of Breast CancerShanghaiChina
| | - Ke‐Da Yu
- Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Shanghai Medical CollegeFudan UniversityShanghaiChina
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Vitale SR, Ruigrok-Ritstier K, Timmermans AM, Foekens R, Trapman-Jansen AMAC, Beaufort CM, Vigneri P, Sleijfer S, Martens JWM, Sieuwerts AM, Jansen MPHM. The prognostic and predictive value of ESR1 fusion gene transcripts in primary breast cancer. BMC Cancer 2022; 22:165. [PMID: 35151276 PMCID: PMC8840267 DOI: 10.1186/s12885-022-09265-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/02/2022] [Indexed: 11/10/2022] Open
Abstract
Background In breast cancer (BC), recurrent fusion genes of estrogen receptor alpha (ESR1) and AKAP12, ARMT1 and CCDC170 have been reported. In these gene fusions the ligand binding domain of ESR1 has been replaced by the transactivation domain of the fusion partner constitutively activating the receptor. As a result, these gene fusions can drive tumor growth hormone independently as been shown in preclinical models, but the clinical value of these fusions have not been reported. Here, we studied the prognostic and predictive value of different frequently reported ESR1 fusion transcripts in primary BC. Methods We evaluated 732 patients with primary BC (131 ESR1-negative and 601 ESR1-positive cases), including two ER-positive BC patient cohorts: one cohort of 322 patients with advanced disease who received first-line endocrine therapy (ET) (predictive cohort), and a second cohort of 279 patients with lymph node negative disease (LNN) who received no adjuvant systemic treatment (prognostic cohort). Fusion gene transcript levels were measured by reverse transcriptase quantitative PCR. The presence of the different fusion transcripts was associated, in uni- and multivariable Cox regression analysis taking along current clinico-pathological characteristics, to progression free survival (PFS) during first-line endocrine therapy in the predictive cohort, and disease- free survival (DFS) and overall survival (OS) in the prognostic cohort. Results The ESR1-CCDC170 fusion transcript was present in 27.6% of the ESR1-positive BC subjects and in 2.3% of the ESR1-negative cases. In the predictive cohort, none of the fusion transcripts were associated with response to first-line ET. In the prognostic cohort, the median DFS and OS were respectively 37 and 93 months for patients with an ESR1-CCDC170 exon 8 gene fusion transcript and respectively 91 and 212 months for patients without this fusion transcript. In a multivariable analysis, this ESR1-CCDC170 fusion transcript was an independent prognostic factor for DFS (HR) (95% confidence interval (CI): 1.8 (1.2–2.8), P = 0.005) and OS (HR (95% CI: 1.7 (1.1–2.7), P = 0.023). Conclusions Our study shows that in primary BC only ESR1-CCDC170 exon 8 gene fusion transcript carries prognostic value. None of the ESR1 fusion transcripts, which are considered to have constitutive ER activity, was predictive for outcome in BC with advanced disease treated with endocrine treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09265-1.
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Prognostic Factors Effective on Survival in Unifocal Borderline Luminal B HER2-Negative and Triple-Negative Breast Cancers: a Cross-Sectional Study. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03294-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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37
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Frankman ZD, Jiang L, Schroeder JA, Zohar Y. Application of Microfluidic Systems for Breast Cancer Research. MICROMACHINES 2022; 13:152. [PMID: 35208277 PMCID: PMC8877872 DOI: 10.3390/mi13020152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/11/2022] [Accepted: 01/17/2022] [Indexed: 02/06/2023]
Abstract
Cancer is a disease in which cells in the body grow out of control; breast cancer is the most common cancer in women in the United States. Due to early screening and advancements in therapeutic interventions, deaths from breast cancer have declined over time, although breast cancer remains the second leading cause of cancer death among women. Most deaths are due to metastasis, as cancer cells from the primary tumor in the breast form secondary tumors in remote sites in distant organs. Over many years, the basic biological mechanisms of breast cancer initiation and progression, as well as the subsequent metastatic cascade, have been studied using cell cultures and animal models. These models, although extremely useful for delineating cellular mechanisms, are poor predictors of physiological responses, primarily due to lack of proper microenvironments. In the last decade, microfluidics has emerged as a technology that could lead to a paradigm shift in breast cancer research. With the introduction of the organ-on-a-chip concept, microfluidic-based systems have been developed to reconstitute the dominant functions of several organs. These systems enable the construction of 3D cellular co-cultures mimicking in vivo tissue-level microenvironments, including that of breast cancer. Several reviews have been presented focusing on breast cancer formation, growth and metastasis, including invasion, intravasation, and extravasation. In this review, realizing that breast cancer can recur decades following post-treatment disease-free survival, we expand the discussion to account for microfluidic applications in the important areas of breast cancer detection, dormancy, and therapeutic development. It appears that, in the future, the role of microfluidics will only increase in the effort to eradicate breast cancer.
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Affiliation(s)
- Zachary D. Frankman
- Department of Biomedical Engineering, University of Arizona, Tucson, AZ 85721, USA;
| | - Linan Jiang
- Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA;
| | - Joyce A. Schroeder
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA;
| | - Yitshak Zohar
- Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA;
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Shafi S, Kellough DA, Lujan G, Satturwar S, Parwani AV, Li Z. Integrating and validating automated digital imaging analysis of estrogen receptor immunohistochemistry in a fully digital workflow for clinical use. J Pathol Inform 2022; 13:100122. [PMID: 36268080 PMCID: PMC9577060 DOI: 10.1016/j.jpi.2022.100122] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 06/22/2022] [Accepted: 06/24/2022] [Indexed: 11/01/2022] Open
Abstract
Background Design Results Conclusions
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Yoon KH, Park Y, Kang E, Kim EK, Kim JH, Kim SH, Suh KJ, Kim SM, Jang M, Yun BL, Park SY, Shin HC. Effect of Estrogen Receptor Expression Level and Hormonal Therapy on Prognosis of Early Breast Cancer. Cancer Res Treat 2021; 54:1081-1090. [PMID: 34793665 PMCID: PMC9582488 DOI: 10.4143/crt.2021.890] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Accepted: 11/15/2021] [Indexed: 11/21/2022] Open
Abstract
Purpose Estrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1%–10%) of ER expression have been separately defined as ER low positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh). Materials and Methods Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative [ER−]). Results A total of 2,162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1,654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER− patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2, negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER− tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (p=0.418). Conclusion ERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.
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Affiliation(s)
- Kyung-Hwak Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yeshong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eunyoung Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eun-Kyu Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jee Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Se Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Koung Jin Suh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sun Mi Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Mijung Jang
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Bo La Yun
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - So Yeon Park
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hee-Chul Shin
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Kolberg-Liedtke C, Wuerstlein R, Gluz O, Heitz F, Freudenberger M, Bensmann E, du Bois A, Nitz U, Pelz E, Warm M, Ortmann M, Sultova E, Brucker SY, Kates RE, Fehm T, Harbeck N. Phenotype Discordance between Primary Tumor and Metastasis Impacts Metastasis Site and Outcome: Results of WSG-DETECT-PriMet. Breast Care (Basel) 2021; 16:475-483. [PMID: 34720807 DOI: 10.1159/000512416] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 09/17/2020] [Indexed: 11/19/2022] Open
Abstract
Introduction Tumor biological factors of breast cancer (BC) such as hormone receptor (HR) status, HER2 status, and grade can differ in the metastatic cascade from primary to lymph node (LN) metastasis and to distant metastatic tissue. Systematic data regarding therapeutic consequences are yet limited. Methods We conducted a prospectively planned, retrospective cohort study comparing BC phenotype in tissue from primary tumors (PTs), locoregional LN metastases, and disease recurrence (DR). HR and HER2 as well as tumor grade in PTs and DR were obtained by a database search. No centralized biomarker testing was performed. The impact of changes in tumor biological factors on post-recurrence survival (PRS) and overall survival was analyzed. Results PriMet comprises 635 patients (LN tissue in 142 patients). Discrepancies for HR or HER2 status between PT and DR were observed in 18.7 and 21.6% of cases, respectively. For HR status, positivity of PT and negativity of DR was seen more often (13.2%) than vice versa (5.5%). For HER2 status, negativity of the primary and positivity of DR was seen more often (14.9%) than vice versa (6.7%). Discordance was more often observed between PT and LN metastasis compared to LN versus DR. However, numbers were small. Compared to concordant non-triple-negative (TN) disease, concordant TN disease showed significantly inferior PRS. Conclusion We demonstrate receptor discordance to occur relatively frequently between PT, LN metastasis, and DR and to impact patient prognosis. However, clinical consequences of receptor discordance need to be drawn with caution considering clinical aspects as well as tumor biology.
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Affiliation(s)
| | - Rachel Wuerstlein
- Breast Center, Department of Gynecology and Obstetrics, University of Munich and CCCLMU, Munich, Germany.,West German Study Group, Mönchengladbach, Germany
| | - Oleg Gluz
- West German Study Group, Mönchengladbach, Germany.,Evangelical Hospital Bethesda, Breast Center Niederrhein, Mönchengladbach, Germany
| | - Florian Heitz
- Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.,Horst-Schmidt-Klinik Wiesbaden, Wiesbaden, Germany
| | | | - Elena Bensmann
- Abteilung für Gynäkologie, Rotkreuzklinikum München, Munich, Germany
| | - Andreas du Bois
- Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.,Horst-Schmidt-Klinik Wiesbaden, Wiesbaden, Germany
| | - Ulrike Nitz
- West German Study Group, Mönchengladbach, Germany.,Evangelical Hospital Bethesda, Breast Center Niederrhein, Mönchengladbach, Germany
| | | | - Matthias Warm
- Brustzentrum, Krankenhaus Köln-Holweide, Cologne, Germany
| | - Monika Ortmann
- Institut für Pathologie, Universitätsklinikum Köln, Cologne, Germany
| | - Elena Sultova
- Institut für Pathologie, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Sara Y Brucker
- Departement für Frauengesundheit, Universitätsklinikum Tübingen, Tübingen, Germany
| | | | - Tanja Fehm
- Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | - Nadia Harbeck
- Breast Center, Department of Gynecology and Obstetrics, University of Munich and CCCLMU, Munich, Germany.,West German Study Group, Mönchengladbach, Germany
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Radionuclide-Based Imaging of Breast Cancer: State of the Art. Cancers (Basel) 2021; 13:cancers13215459. [PMID: 34771622 PMCID: PMC8582396 DOI: 10.3390/cancers13215459] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/14/2021] [Accepted: 10/14/2021] [Indexed: 12/21/2022] Open
Abstract
Simple Summary Breast cancer is one of the most commonly diagnosed malignant tumors, possessing high incidence and mortality rates that threaten women’s health. Thus, early and effective breast cancer diagnosis is crucial for enhancing the survival rate. Radionuclide molecular imaging displays its advantages for detecting breast cancer from a functional perspective. Noninvasive visualization of biological processes with radionuclide-labeled small metabolic compounds helps elucidate the metabolic state of breast cancer, while radionuclide-labeled ligands/antibodies for receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer. This review focuses on the most recent developments of novel radiotracers as promising tools for early breast cancer diagnosis. Abstract Breast cancer is a malignant tumor that can affect women worldwide and endanger their health and wellbeing. Early detection of breast cancer can significantly improve the prognosis and survival rate of patients, but with traditional anatomical imagine methods, it is difficult to detect lesions before morphological changes occur. Radionuclide-based molecular imaging based on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) displays its advantages for detecting breast cancer from a functional perspective. Radionuclide labeling of small metabolic compounds can be used for imaging biological processes, while radionuclide labeling of ligands/antibodies can be used for imaging receptors. Noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer, contributing to early diagnosis and better management of cancer patients. The rapid development of radionuclide probes aids the diagnosis of breast cancer in various aspects. These probes target metabolism, amino acid transporters, cell proliferation, hypoxia, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), gastrin-releasing peptide receptor (GRPR) and so on. This article provides an overview of the development of radionuclide molecular imaging techniques present in preclinical or clinical studies, which are used as tools for early breast cancer diagnosis.
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Kumar S, Freelander A, Lim E. Type 1 Nuclear Receptor Activity in Breast Cancer: Translating Preclinical Insights to the Clinic. Cancers (Basel) 2021; 13:4972. [PMID: 34638457 PMCID: PMC8507977 DOI: 10.3390/cancers13194972] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 12/30/2022] Open
Abstract
The nuclear receptor (NR) family of transcription factors is intimately associated with the development, progression and treatment of breast cancer. They are used diagnostically and prognostically, and crosstalk between nuclear receptor pathways and growth factor signalling has been demonstrated in all major subtypes of breast cancer. The majority of breast cancers are driven by estrogen receptor α (ER), and anti-estrogenic therapies remain the backbone of treatment, leading to clinically impactful improvements in patient outcomes. This serves as a blueprint for the development of therapies targeting other nuclear receptors. More recently, pivotal findings into modulating the progesterone (PR) and androgen receptors (AR), with accompanying mechanistic insights into NR crosstalk and interactions with other proliferative pathways, have led to clinical trials in all of the major breast cancer subtypes. A growing body of evidence now supports targeting other Type 1 nuclear receptors such as the glucocorticoid receptor (GR), as well as Type 2 NRs such as the vitamin D receptor (VDR). Here, we reviewed the existing preclinical insights into nuclear receptor activity in breast cancer, with a focus on Type 1 NRs. We also discussed the potential to translate these findings into improving patient outcomes.
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Affiliation(s)
- Sanjeev Kumar
- Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, Darlinghurst 2010, Australia; (A.F.); (E.L.)
- Garvan Institute of Medical Research, University of New South Wales, Darlinghurst 2010, Australia
| | - Allegra Freelander
- Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, Darlinghurst 2010, Australia; (A.F.); (E.L.)
- Garvan Institute of Medical Research, University of New South Wales, Darlinghurst 2010, Australia
| | - Elgene Lim
- Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, Darlinghurst 2010, Australia; (A.F.); (E.L.)
- Garvan Institute of Medical Research, University of New South Wales, Darlinghurst 2010, Australia
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Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM, Senn HJ, Winer EP, Gnant M. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol 2021; 32:1216-1235. [PMID: 34242744 PMCID: PMC9906308 DOI: 10.1016/j.annonc.2021.06.023] [Citation(s) in RCA: 481] [Impact Index Per Article: 120.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/22/2021] [Accepted: 06/27/2021] [Indexed: 12/12/2022] Open
Abstract
The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.
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Affiliation(s)
- H J Burstein
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
| | - G Curigliano
- European Institute of Oncology, University of Milan, Milan, Italy.
| | | | - W P Weber
- University of Basel, Basel, Switzerland
| | | | - M M Regan
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - H J Senn
- St. Gallen Oncology Conferences (Foundation SONK), St. Gallen, Switzerland
| | - E P Winer
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - M Gnant
- Medical University of Vienna, Vienna, Austria
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Kunc M, Popęda M, Biernat W, Senkus E. Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer. Cancers (Basel) 2021; 13:cancers13194755. [PMID: 34638241 PMCID: PMC8507533 DOI: 10.3390/cancers13194755] [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: 08/23/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 12/28/2022] Open
Abstract
Estrogen receptor α (ERα) and progesterone receptor (PgR) are crucial prognostic and predictive biomarkers that are usually co-expressed in breast cancer (BC). However, 12-24% of BCs present ERα(+)/PgR(-) phenotype at immunohistochemical evaluation. In fact, BC may either show primary PgR(-) status (in chemonaïve tumor sample), lose PgR expression during neoadjuvant treatment, or acquire PgR(-) phenotype in local relapse or metastasis. The loss of PgR expression in ERα(+) breast cancer may signify resistance to endocrine therapy and poorer outcomes. On the other hand, ERα(+)/PgR(-) BCs may have a better response to neoadjuvant chemotherapy than double-positive tumors. Loss of PgR expression may be a result of pre-transcriptional alterations (copy number loss, mutation, epigenetic modifications), decreased transcription of the PGR gene (e.g., by microRNAs), and post-translational modifications (e.g., phosphorylation, sumoylation). Various processes involved in the down-regulation of PgR have distinct consequences on the biology of cancer cells. Occasionally, negative PgR status detected by immunohistochemical analysis is paradoxically associated with enhanced transcriptional activity of PgR that might be inhibited by antiprogestin treatment. Identification of the mechanism of PgR loss in each patient seems challenging, yet it may provide important information on the biology of the tumor and predict its responsiveness to the therapy.
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Affiliation(s)
- Michał Kunc
- Department of Pathomorphology, Medical University of Gdańsk, 80-214 Gdańsk, Poland; (M.K.); (W.B.)
| | - Marta Popęda
- Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, 80-211 Gdańsk, Poland;
| | - Wojciech Biernat
- Department of Pathomorphology, Medical University of Gdańsk, 80-214 Gdańsk, Poland; (M.K.); (W.B.)
| | - Elżbieta Senkus
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, 80-214 Gdańsk, Poland
- Correspondence: ; Tel.: +48-58-584-4481
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Xie P, An R, Yu S, He J, Zhang H. A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape. J Transl Med 2021; 19:398. [PMID: 34544424 PMCID: PMC8454077 DOI: 10.1186/s12967-021-03076-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 09/10/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND The diversity and plasticity behind ER+/PR-/HER2- breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. METHODS Based on the immune-related gene expression profiles of 411 ER+/PR-/HER2- breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. RESULTS Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. CONCLUSION Overall, this study revealed five heterogeneous immune subtypes among ER+/PR-/HER2- breast cancer, also provided important implications for clinical translations.
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Affiliation(s)
- Peiling Xie
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, 710061, Xi'an, People's Republic of China
| | - Rui An
- Department of Hepatological Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, 710061, Xi'an, People's Republic of China
| | - Shibo Yu
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, 710061, Xi'an, People's Republic of China
| | - Jianjun He
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, 710061, Xi'an, People's Republic of China.
| | - Huimin Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, 710061, Xi'an, People's Republic of China.
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Park YH, Karantza V, Calhoun SR, Park S, Lee S, Kim JY, Yu JH, Kim SW, Lee JE, Nam SJ, Aktan G, Marsico M. Prevalence, treatment patterns, and prognosis of low estrogen receptor-positive (1% to 10%) breast cancer: a single institution's experience in Korea. Breast Cancer Res Treat 2021; 189:653-663. [PMID: 34487293 DOI: 10.1007/s10549-021-06309-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 06/22/2021] [Indexed: 01/22/2023]
Abstract
PURPOSE To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)-expressing invasive breast cancer. METHODS This retrospective, non-interventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathological characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-low (1% to 10%) and ER-high (> 10%) according to the Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test. RESULTS 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-low tumors: 63 (53.8%) of whom had HER2- tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-high/HER2- cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-low/HER2- (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS. CONCLUSION Patients with ER-low/HER2- breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-low/HER2- disease.
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Affiliation(s)
- Yeon Hee Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-Gu, Seoul, 06351, South Korea.
| | | | | | - Seri Park
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sohee Lee
- Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, South Korea
| | - Ji-Yeon Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-Gu, Seoul, 06351, South Korea
| | - Jong Han Yu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seok Won Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jeong Eon Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seok Jin Nam
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Dieci MV, Griguolo G, Bottosso M, Tsvetkova V, Giorgi CA, Vernaci G, Michieletto S, Angelini S, Marchet A, Tasca G, Genovesi E, Cumerlato E, Lo Mele M, Conte P, Guarneri V. Impact of estrogen receptor levels on outcome in non-metastatic triple negative breast cancer patients treated with neoadjuvant/adjuvant chemotherapy. NPJ Breast Cancer 2021; 7:101. [PMID: 34341356 PMCID: PMC8329161 DOI: 10.1038/s41523-021-00308-7] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 06/25/2021] [Indexed: 12/13/2022] Open
Abstract
Although 1% is the recommended cut-off to define estrogen receptor (ER) positivity, a 10% cut-off is often used in clinical practice for therapeutic purposes. We here evaluate clinical outcomes according to ER levels in a monoinstitutional cohort of non-metastatic triple-negative breast cancer (BC) patients undergoing (neo)adjuvant chemotherapy. Clinicopathological data of 406 patients with ER < 10% HER2-negative BC treated with (neo)adjuvant chemotherapy between 01/2000 and 04/2019 were collected. Patients were categorized in ER-negative (ER < 1%; N = 364) and ER-low positive (1-9%, N = 42). At a median follow-up of 54 months, 88 patients had relapsed and 64 died. No significant difference was observed in invasive relapse-free survival (iRFS) and overall survival (OS) according to ER expression levels, both at univariate and multivariate analysis (5-years iRFS 74.0% versus 73.1% for ER-negative and ER-low positive BC, respectively, p = 0.6; 5-years OS 82.3% versus 76.7% for ER-negative and ER-low positive BC, respectively, p = 0.8). Among the 165 patients that received neoadjuvant chemotherapy, pathological complete response rate was similar in the two cohorts (38% in ER-negative, 44% in ER-low positive, p = 0.498). In conclusion, primary BC with ER1-9% shows similar clinical behavior to ER 1% BC. Our results suggest the use of a 10% cut-off, rather than <1%, to define triple-negative BC.
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Affiliation(s)
- Maria Vittoria Dieci
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Gaia Griguolo
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Michele Bottosso
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | | | | | - Grazia Vernaci
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | | | - Silvia Angelini
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
| | - Alberto Marchet
- Clinica Chirurgica 1, Azienda Ospedaliera di Padova, Padova, Italy
| | - Giulia Tasca
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
| | - Elisa Genovesi
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Enrico Cumerlato
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Marcello Lo Mele
- Department of Pathology, Azienda Ospedaliera di Padova, Padova, Italy
| | - PierFranco Conte
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Valentina Guarneri
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
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Yu KD, Cai YW, Wu SY, Shui RH, Shao ZM. Estrogen receptor-low breast cancer: Biology chaos and treatment paradox. Cancer Commun (Lond) 2021; 41:968-980. [PMID: 34251757 PMCID: PMC8504145 DOI: 10.1002/cac2.12191] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 04/23/2021] [Accepted: 06/19/2021] [Indexed: 02/03/2023] Open
Abstract
Hormone receptor testing mainly serves the purpose of guiding treatment choices for breast cancer patients. Patients with estrogen receptor (ER)‐positive breast cancers show significant response to endocrine therapy. However, the methods to define ER status and eligibility for treatment remain controversial. Despite recent guidelines considering staining ≥1% of tumor nuclei by immunohistology as ER‐positive, it has raised concerns on the benefit of endocrine therapy for tumors with ER 1%‐10% expression, termed “ER‐low positive”. This subgroup accounts for 3% to 9% of all patients and is likely to have unique molecular features, and therefore distinct therapeutic response to endocrine therapy compared with ER‐high positive tumors. The latest guidelines did not provide detailed descriptions for those patients, resulting in inconsistent treatment strategies. Consequently, we aimed to resolve this dilemma comprehensively. This review discusses molecular traits and recent ER‐low positive breast cancer innovations, highlighting molecular‐targeted treatment rather than traditional unified endocrine therapy for future basic and clinical research.
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Affiliation(s)
- Ke-Da Yu
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.,Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China
| | - Yu-Wen Cai
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.,Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China
| | - Song-Yang Wu
- Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China
| | - Ruo-Hong Shui
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China
| | - Zhi-Ming Shao
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.,Shanghai Key Laboratory of Breast Cancer, Shanghai, 200032, P. R. China
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Ahirwar R, Khan N, Kumar S. Aptamer-based sensing of breast cancer biomarkers: a comprehensive review of analytical figures of merit. Expert Rev Mol Diagn 2021; 21:703-721. [PMID: 33877005 DOI: 10.1080/14737159.2021.1920397] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Accurate determination of the aberrantly expressed biomarkers such as human epidermal growth factor receptor 2 (HER2), carcinoembryonic antigen (CEA), platelet-derived growth factor (PDGF), mucin 1 (MUC1), and vascular endothelial growth factor VEGF165 have played an essential role in the clinical management of the breast cancer. Assessment of these cancer-specific biomarkers has conventionally relied on time-taking methods like the enzyme-linked immunosorbent assay and immunohistochemistry. However, recent development in the aptamer-based diagnostics has allowed developing tools that may substitute the conventional means of biomarker assessment in breast cancer. Adopting the aptamer-based diagnostic tools (aptasensors) to clinical practices will depend on their analytical performance on clinical samples. AREAS COVERED In this review, we provide an overview of the analytical merits of HER2, CEA, PDGF, MUC1, and VEGF165 aptasensors. Scopus and Pubmed databases were searched for studies reporting aptasensor development for the listed breast cancer biomarkers in the past one decade. Linearity, detection limit, and response time are emphasized. EXPERT OPINION In our opinion, aptasensors have proven to be on a par with the antibody-based methods for detection of various breast cancer biomarkers. Though robust validation of the aptasensors on significant sample size is required, their ability to detect pathophysiological range of biomarkers suggest the possibility of future clinical adoption.
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Affiliation(s)
- Rajesh Ahirwar
- Department of Environmental Biochemistry, ICMR- National Institute for Research in Environmental Health, Bhopal, India
| | - Nabab Khan
- Department of Environmental Biochemistry, ICMR- National Institute for Research in Environmental Health, Bhopal, India
| | - Saroj Kumar
- School of Biosciences, Apeejay Stya University, Gurgaon, India
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Ronchi A, Pagliuca F, Zito Marino F, Accardo M, Cozzolino I, Franco R. Current and potential immunohistochemical biomarkers for prognosis and therapeutic stratification of breast carcinoma. Semin Cancer Biol 2021; 72:114-122. [PMID: 32165319 DOI: 10.1016/j.semcancer.2020.03.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/01/2020] [Accepted: 03/05/2020] [Indexed: 01/16/2023]
Abstract
The identification of biomarkers on cancer tissue samples could be obtained through several technologies. In this setting, the immunohistochemistry and in situ hybridization are accessible in most pathology laboratories. Particularly, immunohistochemistry can be used not only for diagnostic issues, but also to define prognostic classes and to define response to specific therapies. Particularly the last applications have been firstly developed in the breast cancer pathology. In addition, the development of molecular classification proposed some prognostic/predictive classes that could be easily defined by immunohistochemistry. Thus, the role of the pathologists has become increasingly important in the definition of prognosis and in the choice therapy, because the immunohistochemical biomarkers are used to guide treatment, to classify breast cancer into biologically and prognostically distinct subtypes. In this review, we will provide information on the current application of the immunohistochemical biomarkers useful in the management of breast cancer patients. Moreover, we consider the application of immunohistochemistry in the definition of the most promising biomarkers derived from molecular studies of the breast cancer, that in the future could integrate the characterization of breast cancer into clinical practice.
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Affiliation(s)
- Andrea Ronchi
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Via Luciano Armanni 5, 80100, Naples, Italy
| | - Francesca Pagliuca
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Via Luciano Armanni 5, 80100, Naples, Italy
| | - Federica Zito Marino
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Via Luciano Armanni 5, 80100, Naples, Italy
| | - Marina Accardo
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Via Luciano Armanni 5, 80100, Naples, Italy
| | - Immacolata Cozzolino
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Via Luciano Armanni 5, 80100, Naples, Italy
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Via Luciano Armanni 5, 80100, Naples, Italy.
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