Clinical Management of BRCA Mutation Carriers
The benefits of PSA screening in BRCA carriers are currently unknown; however, there have been suggestions (based on very small studies) that PSA levels at prostate cancer diagnosis may be higher in carriers than non-carriers.[220,221] These findings suggest that PSA screening may be of potential utility in men with BRCA mutations, especially in view of the aggressive phenotype. Preliminary results of the IMPACT PSA screening study reported a positive predictive value of 47.6% in 21 BRCA2 carriers undergoing biopsy on the basis of elevated PSA. Since screening these men detected clinically significant prostate cancer, the authors suggest that these findings provide rationale for continued screening in such men; however, a survival benefit from such screening has not been shown. Ultimately, it is possible that information on BRCA mutation status in men may inform optimal screening and treatment strategies. Furthermore, recent data that the presence of a germline BRCA2 mutation is an independent prognostic factor for survival in prostate cancer led these authors to conclude that active surveillance may not be the optimal management strategy due to the aggressive disease phenotype.
Based on the NCCN clinical practice guidelines, screening guidelines for male breast cancer BRCA mutation carriers includes monthly breast self exams, clinical breast exam semiannually, and consideration of a baseline mammogram. Annual mammogram is a consideration with the presence of gynecomastia or parenchymal/glandular breast density of baseline study. Furthermore, screening guidelines for prostate cancer include PSA screening and digital rectal exam on an annual basis starting at age 40 years.
Reproductive Considerations in BRCA Mutation Carriers
Refer to the Prenatal diagnosis and preimplantation genetic diagnosis section in the Psychosocial Issues in Inherited Breast Cancer Syndromes section of this summary for more information.
Prognosis of BRCA1- and BRCA2-related breast cancer
BRCA1-related breast cancer
The distinct features of BRCA1-associated breast tumors are important in prognosis. In addition, there appears to be accelerated growth in BRCA1-associated breast cancer, which is suggested by high-proliferation indices and absence of the expected correlation of tumor size with lymph node status. These pathological features are associated with a worse prognosis in breast cancer, and early studies suggested that BRCA1 mutation carriers with breast cancer may have a poorer prognosis compared with sporadic cases.[225,226,227] These studies particularly noted an increase in ipsilateral and contralateral second primary breast cancers in BRCA1 mutation carriers.[228,229] A retrospective cohort study found a 47.4% incidence of contralateral cancer 25 years after the first breast cancer. BRCA1 carriers had a risk 1.6 times higher than BRCA2 carriers, and risk was higher when the first breast cancer occurred before age 40 years. A retrospective cohort study of 496 Ashkenazi Jewish (AJ) breast cancer patients from two centers compared the relative survival among 56 BRCA1/BRCA2 mutation carriers followed for a median of 116 months. BRCA1 mutations were independently associated with worse disease-specific survival. The poorer prognosis was not observed in women who received chemotherapy. A large population-based study of incident cases of breast cancer among women in Israel failed to find a difference in OS for carriers of BRCA1 founder mutations (n = 76) compared with noncarriers (n = 1,189). Similar findings were seen in a European cohort with no differences in disease-free survival in BRCA1-associated breast cancers.