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BRCA1 promoter methylation in breast cancer patients is associated with response to olaparib/eribulin combination

Asuka Kawachi1,2, Satoshi Yamashita1, Eriko Okochi-Takada1

  • 1Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.

Breast Cancer Research and Treatment
|April 22, 2020
PubMed
Abstract

Insights

Poly (ADP-ribose) polymerase (PARP) inhibitors show promise for triple-negative breast cancer (TNBC) patients with BRCA mutations. High BRCA1 promoter methylation combined with mutations may identify TNBC patients who benefit from olaparib/eribulin therapy.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • PARP inhibitors are effective in breast cancer with BRCA1/2 germline mutations.
  • Efficacy of PARP inhibitors in breast cancer with BRCA1 promoter methylation is not well-established.
  • Triple-negative breast cancer (TNBC) presents unique treatment challenges.

Purpose of the Study:

  • To investigate the efficacy of olaparib/eribulin combination therapy in TNBC patients.
  • To evaluate the role of BRCA1 promoter methylation in predicting treatment response.
  • To identify biomarkers for selecting TNBC patients who benefit from PARP inhibition.

Main Methods:

  • Analysis of biopsy samples from 32 TNBC patients treated with eribulin/olaparib.
  • Mutation analysis using FoundationOne CDx.
  • Quantitative methylation-specific PCR and bisulfite sequencing for BRCA1 promoter methylation levels.

Main Results:

  • One of 20 evaluable TNBC patients had high BRCA1 promoter methylation (>80%) and achieved complete response.
  • Five patients had low BRCA1 promoter methylation (30-80%); one with a BRCA2 mutation showed long-term disease control (24 weeks).
  • Patients with BRCA1/2 mutations or high BRCA1 promoter methylation demonstrated improved 6-month progression-free survival (PFS) (P=0.009).

Conclusions:

  • Quantitative methylation analysis suggests that homozygous BRCA1 promoter methylation combined with mutations may better identify TNBC patients responsive to olaparib/eribulin.
  • BRCA1 promoter methylation status is a potential predictive biomarker for PARP inhibitor therapy in TNBC.
  • Further research is warranted to validate these findings and optimize treatment strategies for TNBC.
Keywords:
BRCA1DNA methylationPARP inhibitorRAD51CTriple-negative breast cancer

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