Therapeutic Implications of Pathogenic Variants in Metastatic Breast Cancer

By: Chris Schimpf, MSW
Posted: Friday, October 18, 2024

In a study of patients with hormone receptor (HR)-positive metastatic breast cancer and pathogenic variants of the BRCA1, BRCA2, or PALB2 genes, Stephanie L. Graff, MD, FACP, FASCO, of Lifespan Cancer Institute and Legorreta Cancer Center at Brown University, Providence, Rhode Island, and colleagues reported the need for further prospective analysis to evaluate the optimal sequence of targeted therapies such as CDK4/6 and PARP inhibitors, establish the germline status of the variants, and examine the status and targeting of mutations of the PIK3CA gene. They presented their findings comparing the genomic signatures and clinical results of patients treated with these targeted agents at the European Society for Medical Oncology (ESMO) Congress 2024 (Abstract 342MO).

A total of 11,650 patients with HR-positive metastatic breast cancer underwent DNA/RNA sequencing, with somatic testing performed. Of that total, 628 were found to have pathogenic variants of the BRCA1 (19%), BRCA2 (66%), or PALB2 (15%) genes. Participants were 96% female and had a median age of 57 (range = 23–90+ years).

Overall, the investigators reported that patients with HR-positive metastatic breast cancer plus one of the pathogenic variants had a poor prognosis compared with those with HR-positive metastatic breast cancer alone, including when treated with CDK4/6 inhibitors (hazard ratio [HR] = 1.25; 95% confidence interval [CI] = 1.10–1.42; P < .001). They further reported that patients treated first with CDK4/6 inhibitors followed by PARP inhibitors (n = 76) had better—but nonsignificant—overall survival rates than those treated with the reverse (n = 7; HR = 1.07; P = .90).

Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.

ESMO Congress 2024

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