Outcomes With Immunotherapy in Hormone Receptor-Positive Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer has historically shown limited response to immunotherapy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of immunotherapy in this patient population.

METHODS

A systematic search of PubMed, Embase, MEDLINE, ClinicalTrials.gov, and Cochrane Library was conducted through May 2025, following PRISMA guidelines. Eligible studies included clinical trials assessing immunotherapy, either alone or in combination, in HR+/HER2- breast cancer, reporting clinical outcomes. Meta-analyses were performed using random-effects models, with pooled risk ratios (RRs) and event rates. Heterogeneity was assessed using I ² statistics.

RESULTS

A total of 11 randomized controlled trials involving 7480 patients (3742 immunotherapy, 3738 control) were included. Immunotherapy did not significantly improve overall response rate (RR: 1.20; 95% CI: 0.92-1.55) or partial response rate (RR: 1.03; 95% CI: 0.54-1.94) compared with control, though it was associated with improved complete response (RR: 1.63; 95% CI: 1.34-1.97). Immunotherapy was also associated with higher therapy-related adverse events (RR: 1.29; 95% CI: 1.04-1.60). Pooled median overall survival and progression-free survival were 23.6 and 6.6 months, respectively. The pooled complete response, partial response, stable disease, and progressive disease rates were 9, 27, 51, and 23%, respectively. Overall mortality in the immunotherapy group was 4%.

CONCLUSIONS

Immunotherapy may modestly enhance complete response rates in HR+/HER2- breast cancer but is associated with increased toxicity and lacks consistent improvements in overall or progression-free survival. Further biomarker-driven trials are warranted.