Olaparib Shows Promise in Metastatic Breast Cancer With Certain Genetic Mutations

Study finds olaparib effective in patients with germline PALB2 mutations and somatic BRCA1/2 mutations

Published on Feb. 10, 2026

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A phase II study found that the PARP inhibitor olaparib was active in patients with metastatic breast cancer who had germline PALB2 mutations or somatic BRCA1/2 mutations. The study showed promising response rates and progression-free survival in these patient populations, expanding the potential use of PARP inhibitors beyond just those with germline BRCA1/2 mutations.

Why it matters

This study broadens the potential patient population that could benefit from PARP inhibitor therapy for metastatic breast cancer, moving beyond just those with germline BRCA1/2 mutations to also include those with germline PALB2 mutations and somatic BRCA1/2 mutations. This could lead to more treatment options for certain breast cancer patients.

The details

The phase II Translational Breast Cancer Research Consortium (TBCRC) 048 study enrolled 54 patients with metastatic breast cancer - 24 with germline PALB2 mutations and 30 with somatic BRCA1/2 mutations. Patients received the PARP inhibitor olaparib at 300 mg twice daily. The study found an objective response rate of 75% in the germline PALB2 mutation cohort and 36.7% in the somatic BRCA1/2 mutation cohort. Median progression-free survival was 9.4 months and 5.5 months, respectively, in the two cohorts. Grade 3 treatment-related adverse events occurred in 24% of patients, most commonly anemia and fatigue.

  • The phase II TBCRC 048 study was reported in the Journal of Clinical Oncology in February 2026.

The players

Nadine M. Tung, MD

Corresponding author for the Journal of Clinical Oncology article and affiliated with Harvard Medical School in Boston.

Translational Breast Cancer Research Consortium (TBCRC)

The multicenter clinical trial consortium that conducted the phase II study of olaparib in metastatic breast cancer patients with certain genetic mutations.

AstraZeneca

The pharmaceutical company that supported the TBCRC 048 study of olaparib.

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What they’re saying

“Olaparib is active in [patients with metastatic breast cancer] with gPALB2m and sBRCAm, significantly expanding the population of [patients] with breast cancer likely to benefit from PARP inhibitors beyond gBRCA1/2m carriers.”

— Nadine M. Tung, MD (Journal of Clinical Oncology)

The takeaway

This study demonstrates that PARP inhibitor therapy with olaparib can benefit a broader population of metastatic breast cancer patients beyond just those with germline BRCA1/2 mutations, including those with germline PALB2 mutations and somatic BRCA1/2 mutations. This expands the potential treatment options for certain breast cancer patients.