Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Importance The limited data on cancer phenotypes in men with germlineBRCA1 and BRCA2pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population. Objective To compare the cancer spectrum and frequencies between maleBRCA1andBRCA2PV carriers. Design, Setting, and Participants Retrospective cohort study of 6902 men, including 3651BRCA1and 3251BRCA2PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. Main Outcomes and Measures BRCA1/2status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. Results Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) beingBRCA2PV carriers. Being affected by any cancer was associated with a higher probability of being aBRCA2, rather than aBRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70;P  Conclusions and Relevance Significant differences in the cancer spectrum were observed in maleBRCA2, compared withBRCA1, PV carriers. These data may inform future recommendations for surveillance ofBRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men withBRCA1/2PVs.