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Related Concept Videos

Targeted Cancer Therapies02:57

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Updated: Jun 16, 2025

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
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Niraparib Plus Aromatase Inhibitors for Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer with a

Laura Lema1, José Manuel Pérez-García2,3, Salvador Blanch4

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|June 13, 2025
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Summary

Niraparib plus aromatase inhibitors show promising results for advanced breast cancer patients with BRCA mutations. This combination therapy met its primary endpoint, demonstrating significant clinical benefit and a manageable safety profile.

Keywords:
BRCA mutationHR+/HER2− breast canceradvanced breast canceraromatase inhibitorsniraparib

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Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Niraparib, a poly (adenosine diphosphate-ribose) polymerase inhibitor, demonstrates potential in treating advanced breast cancer with germline BRCA1/2 mutations.
  • Hormone receptor-positive (HR+)/HER2-negative advanced breast cancer often develops resistance to standard therapies, necessitating novel treatment strategies.

Purpose of the Study:

  • To evaluate the efficacy and safety of combining niraparib with aromatase inhibitors (AIs) in patients with HR+/HER2- advanced breast cancer.
  • Specifically assess outcomes in patients with germline BRCA1/2 mutations (cohort A) and explore outcomes in those with wild-type BRCA and homologous recombination deficiency (cohort B).

Main Methods:

  • The LUZERN trial was a multicenter, open-label, phase II clinical trial (NCT04240106).
  • Patients received niraparib (300 mg or 200 mg) in combination with an AI, having received ≤1 line of chemotherapy and 1-2 prior lines of endocrine therapy for advanced disease.
  • The primary endpoint was the clinical benefit rate (CBR) in cohort A (germline BRCA1/2 mutation carriers).

Main Results:

  • 14 patients were enrolled in cohort A; cohort B had no enrollments. The median follow-up was 16.7 months.
  • The CBR in cohort A was 46.2% (95% CI: 19.2-74.9), meeting the primary endpoint.
  • Median progression-free survival was 5.5 months (95% CI: 1.9-8.5), and median overall survival was 18.1 months (95% CI: 9.7-NE). The safety profile was consistent with known drug toxicities.

Conclusions:

  • Niraparib combined with an AI shows encouraging antitumor activity in patients with AI-resistant HR+/HER2- advanced breast cancer and germline BRCA1/2 mutations.
  • The combination therapy demonstrated a manageable safety profile, supporting its potential as a treatment option for this patient population.