F Cardoso1, J M S Bartlett2, L Slaets3, C H M van Deurzen4, E van Leeuwen-Stok5, P Porter6, B Linderholm7, I Hedenfalk8, C Schröder9, J Martens10, J Bayani11, C van Asperen12, M Murray13, C Hudis14, L Middleton15, J Vermeij16, K Punie17, J Fraser18, M Nowaczyk19, I T Rubio20, S Aebi21, C Kelly22, K J Ruddy23, E Winer24, C Nilsson25, L Dal Lago26, L Korde27, K Benstead28, O Bogler29, T Goulioti30, A Peric3, S Litière3, K C Aalders3, C Poncet3, K Tryfonidis3, S H Giordano31. 1. Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal; European Organisation for Research and Treatment of Cancer-Breast Cancer Group, Toronto, Canada. Electronic address: fatimacardoso@fundacaochampalimaud.pt. 2. Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Canada; University of Edinburgh, Edinburgh, UK. 3. European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium. 4. Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands; Dutch Breast Cancer Research Group (BOOG), The Netherlands. 5. Dutch Breast Cancer Research Group (BOOG), The Netherlands. 6. Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA; Department of Pathology, University of Washington, Seattle, USA. 7. Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Swedish Association of Breast Oncologists (SABO), Lund University, Lund, Sweden. 8. Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden. 9. Dutch Breast Cancer Research Group (BOOG), The Netherlands; Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands. 10. Dutch Breast Cancer Research Group (BOOG), The Netherlands; Breast Cancer Genomics and Proteomics Lab, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. 11. Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Canada. 12. Dutch Breast Cancer Research Group (BOOG), The Netherlands; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. 13. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York. 14. Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York; Weill Cornell Medical College, New York. 15. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, USA. 16. Department of Medical Oncology, Hospital Network Antwerp (ZNA), Antwerp, Belgium. 17. Department of General Medical Oncology, UZ Leuven, Leuven, Belgium. 18. Beatson West of Scotland Cancer Centre, Glasgow, UK. 19. Specialist Hospital, St. Wojciech, Gdansk, Poland. 20. Breast Surgical Unit, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 21. Swiss Group for Clinical Cancer Research (SAKK), Switzerland. 22. All Ireland Cooperative Oncology Research Group (ICORG), Ireland. 23. Department of Oncology, Mayo Clinic, Rochester, USA. 24. Dana-Farber Cancer Institute, Boston, USA. 25. Department of Oncology, Västmanlands Hospital, Västerås, Sweden; Swedish Association of Breast Oncologists (SABO), Sweden. 26. Department of Medical Oncology, Jules Bordet Institute, Brussels, Belgium. 27. University of Washington, Seattle, USA. 28. Department of Oncology, Cheltenham General Hospital, UK. 29. Global Academic Programs, University of Texas MD Anderson Cancer Center, Houston, USA. 30. Breast International Group, Brussels, Belgium. 31. Departments of Health Services Research and Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
Abstract
Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.
Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods:Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.
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