Revisiting the impact of BRCA1 pathogenic variants on the aggressiveness of prostate cancer.

BRCA1 pathogenic variants are associated with a lower risk of developing prostate cancer than BRCA2, but aggressiveness remains unclear. Therefore, screening criteria are insufficiently established. Here, we reanalyzed the impact of BRCA1 pathogenic variants on aggressiveness using 11 300 prostate cancer patients, adjusting for age and area. The proportion of aggressive prostate cancer was higher in BRCA1 carriers (86.7%) than in noncarriers (61.1%) (odds ratio = 4.87; 95% confidence interval = 1.05 to 22.60). The proportion of high prostate-specific antigen levels was higher in BRCA1 carriers (66.7%) than in noncarriers (27.9%) (P = 7.61 × 10-3). BRCA1 carriers had a worse tendency than noncarriers for T classification (T3-4: BRCA1, 36.4%; noncarriers, 23.2%) and Gleason score (GS8-10: BRCA1, 53.3%; noncarriers, 31.0%). Moreover, we observed the first case of BRCA1-related aggressive prostate cancer showing long-term survival through early detection and multidisciplinary treatment. These results suggest that recommendations for early prostate cancer screening might need to be reconsidered for BRCA1 carriers.