Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Abstract

BackgroundBRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).MethodsWe characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.ResultsAmong BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12).ConclusionsOn the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0671-y) contains supplementary material, which is available to authorized users.

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

“…23 Pathogenic variants were defined as previously described. 24 All participating studies have been approved by local ethical review committees.…”

Emerging Data and Current Challenges for Young, Old, Obese, or Male Patients with Breast Cancer

“…Up until this point, the vast majority of data on men have come from smaller retrospective studies with limited power to effectively support treatment selection and survivorship issues. There is a suggestion that breast cancer behaves differently in men compared with women, but this is not well understood nor do we know how to act on these differences (72,73). For example, in a study comparing Oncotype DX scores among men and women, although many similarities were noted in scores overall, the mean expression of estrogen and progesterone receptors were higher in men, as were proliferation genes such as Ki-67 (73).…”

Performance of BRCA1/2 mutation prediction models in male breast cancer patients

“…It also shows that genetic tests were performed in some men several years after their diagnosis. Studies of the pathological features of BRCA1/2 MBC tumours showed that these tumours display distinct characteristics compared with BRCA1 / 2 female breast cancer tumours (eg, high histologic grade in BRCA2 MBC patients), which suggested greater biological aggressiveness . Although it is not directly proven for MBC caused by BRCA1/2 mutations, it might be the case that some patients in this specific group were not tested because they did not survive the disease.…”