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

PURPOSE

The predictive ability of plasma 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 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 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 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 mutations was 1.70 (95% CI, 1.05-2.74; =0.03) for OS, which was statistically significant for predicting poor survival, and 1.56 (95% CI, 1.13-2.14; =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, =0.30) for PFS, which indicates that plasma mutation had no effect on PFS after subsequent ET. Subgroup analysis suggested that plasma mutations were correlated with shorter PFS (HR, 1.98; 95% CI, 1.12-3.51; =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; =0.54) or fulvestrant (HR, 1.03; 95% CI, 0.79-1.34; =0.83).

CONCLUSION

The current meta-analysis demonstrates that plasma mutation status is not a predictor of ET efficacy for all drugs without distinction in patients with hormone-receptor-positive advanced breast cancer. mutation predicted a poor response to AIs, whereas it was not predictive of non-AI ET efficacy, especially for fulvestrant.