Brca-Mutated Breast Cancer: The Unmet Need, Challenges and Therapeutic Benefits of Genetic Testing

Authors

Banu Arun
Fergus J Couch
Jean Abraham
Nadine Tung
Peter A Fasching

Language

English

Publication Date

11-1-2024

Journal

British Journal of Cancer

DOI

10.1038/s41416-024-02827-z

PMID

39215191

PMCID

PMC11519381

PubMedCentral® Posted Date

8-30-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Mutations in the BRCA1 and/or BRCA2 genes (BRCAm) increase the risk of developing breast cancer (BC) and are found in ~5% of unselected patients with the disease. BC resulting from a germline BRCAm (gBRCAm) has distinct clinical characteristics along with increased sensitivity to DNA-damaging agents such as poly(ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies, and potentially decreased sensitivity to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Given the evolving treatment landscape for gBRCAm BC in early and advanced disease settings, timely determination of gBRCAm status is fundamental to facilitate the most effective treatment strategy for patients. However, many patients with gBRCAm are not identified due to suboptimal referral rates and/or a low uptake of genetic testing. We discuss current evidence for a differential response to treatment in patients with gBRCAm in early and advanced BC settings, including outcomes with PARP inhibitors, platinum-based chemotherapies, and CDK4/6 inhibitors, as well as ongoing treatment innovations and the potential of these treatment approaches. Current genetic testing strategies are also examined, including the latest guidelines on who and when to test for gBRCAm, as well as challenges to testing and how these may be overcome.

Keywords

Humans, Breast Neoplasms, Female, Genetic Testing, Germ-Line Mutation, BRCA2 Protein, BRCA1 Protein, Poly(ADP-ribose) Polymerase Inhibitors, Genes, BRCA1, Genes, BRCA2, Breast cancer, Breast cancer

Published Open-Access

yes

Recommended Citation

Arun, Banu; Couch, Fergus J; Abraham, Jean; et al., "Brca-Mutated Breast Cancer: The Unmet Need, Challenges and Therapeutic Benefits of Genetic Testing" (2024). Faculty, Staff and Student Publications. 5296.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5296