Expanding the therapeutic scope of PARP inhibitors in breast cancer: current indications and future directions.

Authors

Charlotte S Walmsley, Adela Rodriguez, Panagiotis A Konstantinopoulos, Geoffrey I Shapiro, Sara M Tolaney, Judy E Garber, Filipa Lynce

Published in

The Journal of clinical investigation. Volume 136. Issue 19. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

Homologous recombination repair deficiency (HRD) occurs in approximately 10% of breast tumors and represents a major targetable vulnerability across multiple cancer types. Impairment of the homologous recombination DNA repair pathway - arising through somatic and germline mutations in homologous recombination repair genes, epigenetic mechanisms, and transcriptomic changes - leads to genomic instability and a reliance on error-prone repair mechanisms. Poly (ADP-ribose) polymerase (PARP) inhibitors harness the synthetic lethality of HRD and PARP inhibition, with current approvals encompassing both early-stage and advanced breast cancer in patients with germline BRCA1/2 (gBRCA1/2) mutations. However, emerging evidence suggests efficacy of PARP inhibitors beyond gBRCA1/2-mutated breast cancer to tumors with other homologous recombination repair defects that confer a "BRCAness" phenotype. This Review examines opportunities to broaden the use of PARP inhibitors in breast cancer and underscores the importance of innovative biomarkers, combination strategies, and next-generation agents to maximize therapeutic impact.

PMID:
42820288
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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