Scientific publications

Characterization of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

Oct 28, 2017 | Magazine: Annals of Oncology

Cardoso F (1), Bartlett JMS (2), Slaets L (3), van Deurzen CHM (4), van Leeuwen-Stok E (5), Porter P (6), Linderholm B (7), Hedenfalk I (8), Schröder C (9), Martens J (10), Bayani J (11), van Asperen C (12), Murray M (13), Hudis C (14), Middleton L (15), Vermeij J (16), Punie K (17), Fraser J (18), Nowaczyk M (19), Rubio IT (20), Aebi S (21), Kelly C (22), Ruddy KJ (23), Winer E (24), Nilsson C (25), Dal Lago L (26), Korde L (27), Benstead K (28), Bogler O (29), Goulioti T (30), Peric A (3), Litière S (3), Aalders KC (3), Poncet C (3), Tryfonidis K (3), Giordano SH (31).

(1) Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal and EORTC.
(2) Transformative pathology, Ontario Institute for Cancer Research, Toronto, Canada & University of Edinburgh, Scotland, UK.
(3) European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
(4) Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands and BOOG.
(5) Dutch Breast Cancer Research Group (BOOG), The Netherlands.
(6) Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center & Department of Pathology, University of Washington, Seattle, USA.
(7) Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden and Swedish Association of Breast Oncologists (SABO).
(8) Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
(9) Department Medical Oncology, University Medical Center Groningen, The Netherlands and BOOG.
(10) Breast Cancer Genomics and Proteomics Lab, Erasmus Medical Center Rotterdam, The Netherlands and BOOG.
(11) Transformative pathology, Ontario Institute for Cancer Research, Toronto, Canada.
(12) Department of Clinical Genetics, Leiden University Medical Center, The Netherlands and BOOG.
(13) Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
(14) Breast Medicine Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
(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, Scotland, 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) Mayo Clinic, Department of Oncology, Rochester, USA.
(24) Dana-Farber Cancer Institute, Boston, USA.
(25) Department of Oncology, Västmanlands Hospital, Västerås, Sweden and Swedish Association of Breast Oncologists (SABO).
(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.

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 1, a retrospective-joint-analysis of cases diagnosed during a 20-year-period.

Patients with follow-up and tumor samples, treated between 1990-2010, in 93 centers/nine countries. Samples were centrally analyzed in three labs (UK, NL, US).

Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001-2010, 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% ER-positive; 81.9% PR-positive; 96.9% AR-positive (ER, PgR or AR Allred score ≥3); 61.1% Ki67 expression low (<14% positive cells); using 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-breast-cancer-mortality.

Breast-cancer-specific-mortality was higher for men <50 years. Better OS and 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.

Male BC is usually ER, PR, and AR positive, Luminal B-like/HER2-negative. 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, while grade, Ki67, and IHC surrogates were not. Significant improvement in survival over time was observed.

CITATION  Ann Oncol. 2017 Oct 28. doi: 10.1093/annonc/mdx651