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Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis

Authors Zhang K, Hong R, Xu F, Xia W, Kaping L, Qin G, Zheng Q, Lu Q, Shi YX, Yuan ZY, Wang SS

Received 5 May 2018

Accepted for publication 11 June 2018

Published 14 August 2018 Volume 2018:10 Pages 2573—2580

DOI https://doi.org/10.2147/CMAR.S173193

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Kai Zhang,* Ruoxi Hong,* Fei Xu, Wen Xia, Lee Kaping, Ge Qin, Qiufan Zheng, Qianyi Lu, Yan Xia Shi, Zhong Yu Yuan, Shusen Wang

Sun Yat-Sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China

*These authors contributed equally to this work

Background: The clinical implication of plasma ESR1 mutations in the estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who had progressed after prior aromatase inhibitor (AI)-based therapy remains controversial. We conducted the first meta-analysis to investigate the prognostic significance and predictive role of plasma ESR1 mutations in MBC patients with prior exposure to AI therapy.
Materials and methods: We searched PubMed, Embase, and Cochrane Library databases for eligible studies. Meta-analysis was conducted to calculate combined hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). Subgroup and sensitivity analyses were also performed.
Results: This study enrolled a total of 1,530 patients with ER-positive MBC cases from six articles, including 429 ESR1 mutation carriers (28.04%). Meta-analysis demonstrated that plasma ESR1 mutation carriers had significantly worse PFS (HR: 1.40, 95% CI: 1.17–1.66; P<0.0001) and OS (HR: 1.65, 95% CI: 1.36–2.01; P<0.0001) compared to wild-type ESR1. Subgroup analysis showed that plasma ESR1 mutations were associated with shorter PFS after AI-based treatment, but were not significantly predictive of outcome on fulvestrant-containing therapy (HR: 1.26, 95% CI: 0.98–1.62; P=0.077). As for different ESR1 mutations, D538G mutation implied significantly worse PFS (HR: 1.50, 95% CI: 1.18–1.91; P=0.01), while Y537S mutation was not correlated with PFS (HR: 1.65, 95% CI: 0.87–1.73; P=0.134).
Conclusion: The meta-analysis indicated that plasma ESR1 mutation assessment may have prognostic significance and clinical value in guiding further endocrine therapy choice in ER+ MBC patients who received prior AI therapy.

Keywords: ESR1 mutations, breast carcinoma, cfDNA, ctDNA, meta analysis

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