Male BRCA mutation carriers: clinical characteristics and cancer spectrum

Mutations in BRCA1 and BRCA2 (BRCA1/2) genes are associated with an increased risk of breast and ovarian cancers in women. The cancer characteristics of men with BRCA1/2 mutations are less well studied. This study describes the unique cancer characteristics of male BRCA1/2 mutation carriers at our institution.

We performed a retrospective chart review on male patients who were seen between January 2004 and December 2014 and tested positive for a BRCA1/2 mutation. We evaluated clinical characteristics, pathology findings, treatment selection and survival.

A total of 102 male patients were identified who tested positive for a BRCA1/2 deleterious mutation. Of these 102 patients, 33 (32%) had a diagnosis of cancer. Of these 33 patients with cancer, the majority (20 patients) were found to carry a BRCA2 mutation. Median age of cancer diagnosis was 65 years (Range: 35-75 years). Of the 33 patients diagnosed with cancer, 8 had two or more cancers, including 1 patient who had 4 cancers. Prostate cancer was the most commonly diagnosed cancer, seen in 13 patients, 11 of whom were BRCA2 positive. These cancers tended to have higher Gleason scores and elevated PSA levels. The majority of these prostate cancer patients were alive and disease free at a median follow-up of 7.4 years. Male breast cancer was the second most common cancer seen in 9 patients, all of whom were BRCA2 positive. The majority of these cancers were high grade, hormone receptor positive and associated with lymph node metastases. There were no breast cancer related deaths. Other cancers included bladder cancer, pancreatic cancer, melanoma and other skin cancers.

This study describes the cancer characteristics and outcomes of male BRCA1/2 mutation carriers. A third of male BRCA1/2 mutation carriers had a diagnosis of cancer. A significant number of patients (mostly BRCA2 mutation positive) developed multiple cancers, which may have important implications for cancer screening and prevention. Despite having high grade histology and advanced stage at diagnosis, male BRCA1/2 mutation carriers with breast and prostate cancer demonstrated a favorable 5-year survival.