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Olaparib Use in Patients With Metastatic Breast Cancer Harboring Somatic BRCA1/2 Mutations or Mutations in

Elaine M Walsh1, Neha Mangini2, John Fetting3

  • 1Women's Malignancy Disease Group, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD; Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Baltimore, MD.

Clinical Breast Cancer
|January 25, 2022
PubMed
Abstract

Insights

Poly (ADP-ribose) polymerase inhibitors show activity in metastatic breast cancer with somatic BRCA1/2 mutations. These PARP inhibitors were not effective in patients with non-BRCA1/2 homologous recombination repair gene mutations.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective for germline BRCA1/2-mutated breast cancer.
  • Somatic BRCA1/2 or other homologous recombination repair (HRR) gene mutations occur in 5%-10% of breast cancers, with limited data on PARPi efficacy.
  • This study investigates olaparib's use in metastatic breast cancer with somatic BRCA1/2 or non-BRCA1/2 HRR mutations.

Purpose of the Study:

  • To examine the efficacy of olaparib in metastatic breast cancer patients with somatic BRCA1/2 or non-BRCA1/2 HRR mutations.
  • To describe patient demographics, tumor characteristics, mutations, and treatment outcomes.
  • To evaluate safety, tolerability, response rates, and survival.

Main Methods:

  • Retrospective, single-institution study.
  • Identified patients treated with off-label olaparib for metastatic breast cancer.
  • Collected data on demographics, tumor characteristics, mutations, safety, tolerability, response rates, and survival.

Main Results:

  • Four patients with somatic BRCA1/2 mutations showed response to olaparib, with a median progression-free survival of 6.5 months.
  • Three patients with non-BRCA1/2 HRR mutations did not respond, with a median progression-free survival of 3 months.
  • Olapiib demonstrated activity in sBRCA1/2-mutated cancers but not in non-BRCA1/2 HRR-mutated cancers.

Conclusions:

  • Olaparib shows potential activity in metastatic breast cancer with somatic BRCA1/2 mutations.
  • No activity was observed with olaparib in patients with germline or somatic non-BRCA1/2 HRR mutations.
  • This study supports further investigation of PARPi in specific breast cancer mutation profiles.
Keywords:
Breast cancerPARP inhibitorsSomatic BRCA1/2

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