Association between endocrine therapy and survival outcomes in estrogen receptor-low breast cancer: a systematic...

The clinical significance of endocrine therapy (ET) in patients with estrogen receptor-low (ER-low, 1%-10%) breast cancer remains uncertain. Increasing evidence suggests that these tumors differ biologically from typical hormone receptor-positive cancers, raising questions about the true benefit of ET in this subgroup.

This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 1, 2025. Hazard ratios (HRs) with corresponding 95% CIs for time-to-event outcomes were extracted directly or estimated from Kaplan-Meier curves when not explicitly reported. Pooled analyses were performed using random-effects models to account for between-study heterogeneity. The protocol was registered in PROSPERO (CRD420251055521).

A total of 6 retrospective observational studies involving 8765 patients with estrogen receptor-low breast cancer were included. Endocrine therapy was associated with improved overall survival (OS) (HR 0.81, 95% CI 0.69-0.95; P = .01; I2 = 0%) and disease-free survival (DFS) (HR 0.64, 95% CI 0.45-0.90; P = .01; I2 = 0%).

Endocrine therapy was associated with improved OS and DFS in patients with estrogen receptor-low breast cancer. These findings suggest that estrogen receptor-low breast cancer should not be uniformly considered endocrine-insensitive and that routine omission of endocrine therapy should be approached cautiously. Given that the available evidence is derived from retrospective observational studies, further prospective studies are needed to identify patients most likely to benefit from endocrine therapy.