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BRCA2 and PSA and prostate cancer

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Germline mutation of the BRCA2 tumour suppressor gene substantially increases the lifetime risk of developing prostate cancer (PCa)

  • in BRCA2-mutation carriers, localized PCa rapidly progresses to metastatic castrate-resistant prostate cancer (mCRPC) with 5-year cancer-specific survival rates of from 50-60% (1,2)
  • BRCA2-mutant tumours also exhibit an increased frequency of intraductal carcinoma (IDC), a pathology that predicts adverse outcome in both familial and sporadic PCa (3,4)

Prostate tumours arising in men with an inactivating BRCA2 germline mutation (BRCA2-mutant PCa) are uniquely aggressive, associated with younger age of onset, have higher rates of lymph node and distant metastasis, and increased mortality relative to sporadic, non-BRCA2-mutant disease (2,4,5)

The molecular origins of the clinical aggressiveness of BRCA2-mutant PCa are unknown.

Screening using PSA in patients with BRCA2 (5):

  • demonstrated that after 3 yr of prostate-specific antigen (PSA) testing, detected more serious prostate cancers in men with BRCA2 mutations than in those without these mutations.
  • study also showed BRCA2 carriers were diagnosed at a younger age (61 vs 64yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01)
  • cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03)
  • no differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers
  • study authors recommended that male BRCA2 carriers are offered systematic PSA screening

Reference:

  • Castro, E. et al. Effect of BRCA mutations on metastatic relapse and causespecific survival after radical treatment for localised prostate cancer. Eur. Urol. 2015; 68:186-193.
  • Castro, E. et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J. Clin. Oncol. 2013; 31: 1748-1757.
  • Risbridger, G. P. et al. Patient-derived xenografts reveal that intraductal carcinoma of the prostate is a prominent pathology in BRCA2 mutation carriers with prostate cancer and correlates with poor prognosis. Eur. Urol. 2015; 67: 496-503
  • Liede, A., Karlan, B. Y. & Narod, S. A. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J. Clin. Oncol. 2004; 22: 735-742
  • Page EC et al. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers. European Journal of Urology (in Press - September 19th 2019)

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