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Clinical significance of gene mutation in ctDNA analysis for hormone receptor-positive metastatic breast cancer

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

A Letter to the Editor to this article was published on 14 March 2020

Abstract

Purpose

In this study, we aim to investigate the mutation spectrum of circulating tumor DNA among hormone receptor-positive metastatic breast cancer (HR-MBC) patients using ultradeep targeted resequencing. In addition, we also evaluate the correlation of mutations detected from this study with progression-free survival (PFS).

Materials and methods

A total of 56 HR-MBC patients were enrolled. Cell-free DNA (cfDNA) was extracted from plasma and sequenced by using Oncomine Breast cancer cfDNA assay in this study.

Result

Concentration of cfDNA is correlated with a number of metastatic organs and serum CEA levels (Spearman’s rank correlation p = 0.0018, p = 0.0015 respectively). Cases with high cfDNA levels (≥ 2.6 ng/μl of plasma) showed worse progression-free survival (PFS) and overall survival compared with cases with low cfDNA levels (p = 0.043 and 0.046, respectively). Among these patients, 29 patients (51.7%) have TP53 mutations, 12 patients (30.3%) have PIK3CA mutations, and 9 patients (16.0%) have ESR1 mutations. Acquisition of ESR1 mutation increased according to the lines of hormone therapy. In addition, patients with ESR1 mutation showed shorter PFS than those without mutation (log-rank p = 0.047). In the multivariate analysis, ESR1 mutation and cfDNA concentration were significant for PFS (p = 0.027 and 0.006, respectively). In conclusion, assessment of ESR1 mutation and cfDNA concentration could be useful in predicting prognosis for HR-MBCs.

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Acknowledgements

We thank Aya Imai and Fumie Sakamoto for their technical support. We would like to convey our gratitude to Dr. Toru Hirota for his constructive suggestions in this study. This study is supported by internal funding of Japanese Foundation for Cancer Research and Novartis Research Grant.

Funding

This study was funded by the Internal funds of JFCR.

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Authors and Affiliations

  1. Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan

    Tomoko Shibayama, Siew-Kee Low & Yusuke Nakamura

  2. Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, Japan

    Tomoko Shibayama, Takayuki Kobayashi, Kokoro Kobayashi, Ippei Fukada, Yoshinori Ito, Takayuki Ueno & Shinji Ohno

  3. Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Makiko Ono & Shunji Takahashi

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  1. Tomoko Shibayama
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Corresponding author

Correspondence to Tomoko Shibayama.

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Conflict of interest

Shunji Takahashi has received research grant for other studies from AstraZeneca, Chugai Pharmaceutical, Eisai, Novartis, Bayer, Taiho, Daiichi-sankyo, and MSD. Yoshinori Ito has received research Grant for other studies from AstraZeneca, Chugai Pharmaceutical, Novartis, EPS, Daiichi-sankyo, Lilly, Kyowa Hakko Kirin, Covance, A2 healthcare, IQVIA, and MSD. Shinji Ono has received research Grant for other studies from Chugai, Eisai, Novartis, Lilly, Pfizer, Taiho, AstraZeneca, and Kyowa Hakko Kirin. Takayuki Ueno received honoraria from Chugai Pharmaceutical, Eisai, Novartis, and Astra Zeneca. Yusuke Nakamura is in an advisory role of Onco Therapy Science, Inc. The other authors declare that they do not have a financial relationship with the organizations that sponsored the research.

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Shibayama, T., Low, SK., Ono, M. et al. Clinical significance of gene mutation in ctDNA analysis for hormone receptor-positive metastatic breast cancer. Breast Cancer Res Treat 180, 331–341 (2020). https://doi.org/10.1007/s10549-019-05512-5

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