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

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.

Figure 1.

(A) Overall survival Kaplan–Meier curves for all patients, by stage of diagnosis. Events considered for this endpoint were death by any cause. (B) Relapse-free survival Kaplan–Meier curves for early breast cancer (M0) patients by nodal status. Events considered for this endpoint were locoregional recurrence, distant progression and death by any cause.

Figure 2.

Overall mortality Kaplan–Meier curves for all patients by time period of diagnosis and by age at diagnosis. Events considered for this endpoint were death by ay cause, the same as for overall survival (the reverse of the mortality numbers).

Figure 3.

(A) Breast cancer–specific mortality Kaplan–Meier curves for all patients by age at diagnosis. Due to missing data, for breast cancer mortality, only deaths following a distant relapse were considered events. All other deaths, not preceded by a distant relapse, were censored on the death date. (B) Kaplan–Meier curves for age-adjusted breast cancer mortality by period of diagnosis. Patients were classified into four age groups (41–50, 51–60, 61–70 and 71–80 years). Patients outside these groups are excluded. The breast cancer–specific mortality was calculated separately for each age group, in each period of diagnosis. The plotted curve corresponds to a weighted analysis, where each of the four age groups receives an equal weight within each period.

Figure 4.

Overall survival Kaplan–Meier curves for early breast cancer (M0) patients (A) according to estrogen receptor (ER) expression (measured by Allred score); (B) according to androgen receptor (AR) expression (measured by Allred score); (C) according to progesterone receptor (PR) expression (measured by Allred score); (D) according to immunohistochemistry (IHC) surrogate of molecular subtype and (E) according to histological grade.