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Review
. 2018 Apr 11;19(5):21.
doi: 10.1007/s11864-018-0540-2.

Update on PARP Inhibitors in Breast Cancer

Alexandra S Zimmer  1 , Mitchell Gillard  2 , Stanley Lipkowitz  3 , Jung-Min Lee  3
Affiliations
Review

Update on PARP Inhibitors in Breast Cancer

Alexandra S Zimmer et al. Curr Treat Options Oncol. .

Abstract

The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer. To date, PARPi seems less efficacious in metastatic breast cancer patients than those with BRCA mutated platinum-sensitive recurrent ovarian cancer, perhaps reflecting the biologic heterogeneity and low somatic BRCA mutation rate in breast cancer. The use of PARPi is gradually evolving, including combination strategies with chemotherapy, targeted agents, radiotherapy, or immunotherapy in women with and without gBRCAm. The role of predictive biomarkers, including molecular signatures and homologous recombination repair deficiency scores based on loss of heterozygosity and other structural genomic aberrations, will be crucial to identify a subgroup of patients who may have benefit from PARPi. An improved understanding of the mechanisms underlying PARPi clinical resistance will also be important to enable the development of new approaches to increase efficacy. This is a field rich in opportunity, and the coming years should see a better understanding of which breast cancer patients we should treat with PARPi and where these agents should come in over the course of treatment.

Keywords: BRCA mutations; Breast cancer; HRR dysfunction; PARP inhibitors.

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Conflict of interest statement

Conflict of Interest

Alexandra S. Zimmer, Mitchell Gillard, Stanley Lipkowitz, and Jung-Min Lee declare they have no conflict of interest.

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