BRCA and Beyond: Impact on Therapeutic Choices Across Cancer

Background: Identifying patients with gBRCAm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management. This review examines the evidence for the latest predictive and therapeutic approaches in BRCA-associated cancers. Clinical Description: Data supports the use of adjuvant olaparib in patients with gBRCAm high-risk HER2-negative breast cancer. In advanced gBRCAm HER2-negative breast cancer, the PARPis talazoparib and olaparib have demonstrated benefit over standard chemotherapy. In ovarian cancer, olaparib, niraparib or rucaparib can be used as monotherapy in frontline maintenance. Olaparib and bevacizumab as a combination can also be used as frontline maintenance. In the relapsed platinum-sensitive setting, olaparib, niraparib and rucaparib are effective maintenance options in BRCAm patients who are PARPi naive. Both olaparib and rucaparib are effective options in BRCAm metastatic castrate-resistant prostate cancer (mCRPC). Evidence also exists for the benefit of PARPi combinations in mCRPC. In metastatic pancreatic cancer, olaparib can be used in gBRCAm patients who are responding to platinum chemotherapy. However, there may be a development of PARPi resistance. Understanding the pathophysiology that contributes to such resistance may allow the development of novel therapeutics. Combination therapy appears to have promising results in emerging trials. Seeking avenues for subsidised genetic testing can reduce the total costs of cancer management, leading to improve detection rates. Conclusion: Identifying breast, ovarian, pancreatic and prostate cancer patients with gBRCAm plays a crucial predictive role in selecting those who will benefit significantly from PARPi therapy. The use of PARPi in gBRCAm HBOC-related cancers has resulted in significant survival benefits. Beyond BRCA1/2, HRR gene assessment and the consideration of other cancer predisposition syndromes may allow more patients to be eligible for and benefit from targeted therapies.