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Real-World Outcomes of CDK4/6 Inhibitors in Germline BRCA1/2-Mutated Hormone Receptor-Positive, HER2-Negative

Mustafa Seyyar1, Ali Kalem2, Mürsel Sali3

  • 1Department of Medical Oncology, Gaziantep City Hospital, Gaziantep 27470, Türkiye.

Current Oncology (Toronto, Ont.)
|June 25, 2026
PubMed

Insights

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors show efficacy in germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). Real-world data suggest potential differences between BRCA1 and BRCA2 carriers, warranting further investigation.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC) represents a distinct subtype.
  • The effectiveness of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in this specific patient population is not fully understood.

Purpose of the Study:

  • To evaluate real-world outcomes in patients with gBRCAm HR+/HER2- MBC treated with CDK4/6 inhibitors plus endocrine therapy.
  • To identify prognostic factors influencing treatment efficacy in this cohort.

Main Methods:

  • Retrospective analysis of a multicenter Turkish cohort (n=121) treated between June 2020 and September 2025.
  • Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier and Cox regression models.
  • Patients received either ribociclib or palbociclib in combination with endocrine therapy.

Main Results:

  • Objective response rate was 69.4%, and clinical benefit rate was 82.6%.
  • Median PFS was 17.0 months and median OS was 47.0 months.
  • While PFS was numerically longer in BRCA1 carriers (25.0 months) versus BRCA2 carriers (14.0 months), this difference was not statistically significant. Fulvestrant-based therapy and ECOG performance status ≥ 1 were associated with shorter PFS and OS.

Conclusions:

  • CDK4/6 inhibitor-based therapy demonstrates significant activity in gBRCAm HR+/HER2- MBC.
  • The observed trend of poorer outcomes in BRCA2 carriers requires further investigation in larger studies.
  • Prognostic factors like ECOG status and choice of endocrine therapy (fulvestrant) impact survival outcomes.
Keywords:
BRCA mutationCDK4/6 inhibitorshormone receptor-positivemetastatic breast cancerpalbociclibreal-world studyribociclib

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