A Case-Based Clinical Approach to the Investigation, Management and Screening of Families with BRCA2 Related Prostate Cancer

Abstract

BRCA2 is the most commonly implicated DNA damage repair gene associated with inherited prostate cancer. BRCA2 deficient prostate cancer typically presents at a younger age, is more poorly differentiated, and is associated with worse survival outcomes than non-BRCA2 associated prostate cancer. Despite these unfavourable prognostic implications, poly-ADP ribose polymerase inhibitors and platinum-based chemotherapy have been identified as potent targeted therapeutic agents towards BRCA1/2 deficient cancer cells. This review article explores the literature surrounding BRCA2-related prostate cancer through a familial clinical scenario. The investigation, diagnosis and management of BRCA2 deficient prostate cancer will be explored, alongside the implications of the identification of a germline pathogenic BRCA2 variant within a family, cascade screening and prostate cancer surveillance in unaffected male BRCA2 carriers. A greater understanding of the molecular pathogenesis of DNA damage repair gene deficient prostate cancer, coupled with new treatment paradigms and widened access to both somatic and germline genetic analysis for prostate cancer patients and their families will hopefully enable the robust implementation of high quality evidence-based clinical pathways for both the management and identification of BRCA2 deficient prostate cancer and improved screening, early detection and prevention strategies for individuals at increased genetic risk of prostate cancer.

Keywords:

• prostate cancer
• BRCA
• genomics
• PARP inhibitors
• clinical management

Acknowledgments

We acknowledge support from The National Institute of Health Research to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. JMcH is supported by the Biomedical Research Centre and the Movember Centre of Excellence and Prostate Cancer UK.

We also would like to thank Rosalind Eeles, Professor of Oncogenetics at the Institute of Cancer Research, Clinician at the Royal Marsden NHS Foundation Trust, for comments on the draft manuscript.

Disclosure

The authors report no conflict of interest in this work.