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The predictive ability of plasma ESR 1 mutations for the efficacy of endocrine therapy in hormone-receptor-positive advanced breast cancer

Authors Du YF, Li N, Jiao X, Li K, Yan SC

Received 18 April 2018

Accepted for publication 26 June 2018

Published 19 September 2018 Volume 2018:11 Pages 6023—6029


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang

Yangfan Du,1 Na Li,1 Xin Jiao,2 Kai Li,1 Shunchao Yan1

1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, People’s Republic of China; 2Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang 110044, People’s Republic of China

Purpose: The predictive ability of plasma ESR1 mutations for outcomes among patients with advanced breast cancer undergoing endocrine therapy (ET) remains disputable. We performed a comprehensive meta-analysis of published studies to clarify the impact of plasma ESR1 mutations on clinical outcomes for patients after subsequent ET.
Materials and methods: An electronic search was performed to identify eligible studies. Studies analyzing progression-free survival (PFS) and/or overall survival (OS) according to plasma ESR1 mutation status after subsequent ET were included. HRs were calculated using a fixed- or random-effects model according to heterogeneity. Pooled HRs and 95% CIs were used to estimate the effects.
Results: Six studies including 705 patients with advanced breast cancer met the inclusion criteria. The impact of plasma ESR1 mutations on PFS and OS after subsequent ET was reported in six studies (seven groups) and two studies, respectively. Meta-analysis results showed that the pooled HR for ESR1 mutations was 1.70 (95% CI, 1.05–2.74; P=0.03) for OS, which was statistically significant for predicting poor survival, and 1.56 (95% CI, 1.13–2.14; P=0.006) for PFS; however, Begg’s and Egger’s test results identified the presence of bias. The trim-and-fill method was used, and after incorporation of the imputed studies, the HR was 1.16 (95% CI, 0.88–1.53, P=0.30) for PFS, which indicates that plasma ESR1 mutation had no effect on PFS after subsequent ET. Subgroup analysis suggested that plasma ESR1 mutations were correlated with shorter PFS (HR, 1.98; 95% CI, 1.12–3.51; P=0.02) in patients subsequently treated with aromatase inhibitors (AIs), whereas no association with PFS was observed for patients subsequently treated with non-AI ET (HR, 1.08; 95% CI, 0.85–1.38; P=0.54) or fulvestrant (HR, 1.03; 95% CI, 0.79–1.34; P=0.83).
Conclusion: The current meta-analysis demonstrates that plasma ESR1 mutation status is not a predictor of ET efficacy for all drugs without distinction in patients with hormone-receptor-positive advanced breast cancer. ESR1 mutation predicted a poor response to AIs, whereas it was not predictive of non-AI ET efficacy, especially for fulvestrant.

Keywords: ESR1 mutation, breast cancer, endocrine therapy, efficacy predictor

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