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01-06-2020 | Breast Cancer | Preclinical study

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

Authors: Asuka Kawachi, Satoshi Yamashita, Eriko Okochi-Takada, Akihiro Hirakawa, Hitoshi Tsuda, Akihiko Shimomura, Yuki Kojima, Kan Yonemori, Yasuhiro Fujiwara, Takayuki Kinoshita, Toshikazu Ushijima, Kenji Tamura

Published in: Breast Cancer Research and Treatment | Issue 2/2020

Abstract

Background

A PARP inhibitor is effective in breast cancer patients with BRCA1/2 germline mutations, and in cell lines with BRCA1 promoter methylation. However, its efficacy in breast cancer patients with BRCA1 promoter methylation is still unknown.

Methods

Biopsy samples were obtained from 32 triple-negative breast cancer (TNBC) patients treated with eribulin/olaparib combination therapy in a clinical trial (UMINID: 000009498) and analyzed for their mutations by FoundationOne CDx. DNA methylation was evaluated by quantitative methylation-specific PCR and bisulfite sequencing, and its level was adjusted for tumor cell fraction.

Results

Among 20 TNBC patients evaluable for both methylation and mutations, one (5%) and five (25%) patients had a high (> 80%) and low (30–80%) BRCA1 promoter methylation levels, respectively. One patient with a high methylation level, also having a BRCA2 mutation of unknown significance, displayed complete response. Among the 5 patients with low methylation levels, only one patient with a BRCA2 mutation of unknown significance displayed long-lasting disease control (24 weeks). Patients with a BRCA1 or BRCA2 mutation, or high BRCA1 promoter methylation showed better 6-month progression-free survival (PFS) compared with the other patients (P = 0.009).

Conclusion

Quantitative methylation analysis suggested that addition of homozygous BRCA1 promoter methylation to mutations may more accurately identify TNBC patients who would benefit from olaparib/eribulin combination therapy. (209 words)

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Title: BRCA1 promoter methylation in breast cancer patients is associated with response to olaparib/eribulin combination therapy
Authors: Asuka Kawachi
Satoshi Yamashita
Eriko Okochi-Takada
Akihiro Hirakawa
Hitoshi Tsuda
Akihiko Shimomura
Yuki Kojima
Kan Yonemori
Yasuhiro Fujiwara
Takayuki Kinoshita
Toshikazu Ushijima
Kenji Tamura
Publication date: 01-06-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 2/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05647-w

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Abstract

Background

Methods

Results

Conclusion

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