Prostate cancer risk, screening and management in patients with germline BRCA1/2 mutations

Nat Rev Urol. 2023 Apr;20(4):205-216. doi: 10.1038/s41585-022-00680-4. Epub 2023 Jan 4.

Abstract

Mutations in the BRCA1 and BRCA2 tumour suppressor genes are associated with prostate cancer risk; however, optimal screening protocols for individuals with these mutations have been a subject of debate. Several prospective studies of prostate cancer incidence and screening among BRCA1/2 mutation carriers have indicated at least a twofold to fourfold increase in prostate cancer risk among carriers of BRCA2 mutations compared with the general population. Moreover, BRCA2 mutations are associated with more aggressive, high-grade disease characteristics at diagnosis, more aggressive clinical behaviour and greater prostate cancer-specific mortality. The risk for BRCA1 mutations seems to be attenuated compared with BRCA2. Prostate-specific antigen (PSA) measurement or prostate magnetic resonance imaging (MRI) alone is an imperfect indicator of clinically significant prostate cancer; therefore, BRCA1/2 mutation carriers might benefit from refined risk stratification strategies. However, the long-term impact of prostate cancer screening is unknown, and the optimal management of BRCA1/2 carriers with prostate cancer has not been defined. Whether timely localized therapy can improve overall survival in the screened population is uncertain. Long-term results of prospective studies are awaited to confirm the optimal screening strategies and benefits of prostate cancer screening among BRCA1/2 mutation carriers, and whether these approaches ultimately have a positive impact on survival and quality of life in these patients.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Early Detection of Cancer / methods
  • Genes, BRCA1
  • Genetic Predisposition to Disease
  • Germ Cells / pathology
  • Humans
  • Male
  • Mutation
  • Prospective Studies
  • Prostate-Specific Antigen / genetics
  • Prostatic Neoplasms* / diagnosis
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / therapy
  • Quality of Life

Substances

  • Prostate-Specific Antigen
  • BRCA2 Protein
  • BRCA1 protein, human
  • BRCA1 Protein