Risk Prediction Tools Available for Germline BRCA1/2 Mutations Underperform in Prostate Cancer Patients

Early identification of germline BRCA1/2 mutations may be relevant for the management of patients with prostate cancer (PC) and to prevent future breast and ovarian cancers in their relatives. Several prediction tools have been developed to estimate the likelihood of a germline BRCA1/2 mutation and are widely used to optimize screening in breast and ovarian cancer patients. We aimed to elucidate the proportion of PC patients with known BRCA1/2 mutations who would have qualified for testing using two risk calculation models (BRCAPRO and the Manchester scoring system [MSS]). We analyzed 106 families with known BRCA1/BRCA2 mutations, including 23 with PC cases. Only 30% and 48% of PC patients who were known BRCA1/BRCA2 mutations carriers would have qualified for testing using BRCAPRO and MSS, respectively. A median of two breast and/or ovarian cancer cases per family had occurred between the first PC identified in a carrier and the cancer case leading to germline testing. PATIENT SUMMARY: We tested two models developed to predict the probability of inherited BRCA1/BRCA2 mutations and found that these tools underperform in men with prostate cancer and should not be used to optimize testing in this population.