激素受体阳性乳腺癌的新辅助免疫治疗：从肿瘤微环境重编程到联合治疗策略

Breast cancer remains the most prevalent malignancy among women worldwide, with hormone receptor-positive (HR+) tumors comprising approximately 70% of cases. Traditionally, HR+ breast cancer has been classified as immunologically "cold" due to its low PD-L1 expression, reduced tumor-infiltrating lymphocytes, and low tumor mutational burden, collectively limiting immunotherapy responsiveness.

However, emerging evidence indicates significant molecular heterogeneity within HR+ tumors, characterized by specific genetic signatures and features of the tumor microenvironment (TME) that can be therapeutically reprogramed through chemotherapy-induced immunogenic cell death combined with immune checkpoint inhibition.

Recent clinical trials demonstrate that biomarker-selected immune-enriched HR+ subsets, identified by MammaPrint Ultra-High 2 classification, homologous recombination deficiency, or elevated tumor-infiltrating lymphocytes, achieve notable pathological complete response rates with immune checkpoint inhibitor combinations. This review summarizes the dynamic interactions between genetic determinants and TME plasticity in HR+ breast cancer and critically assesses combination strategies across 31 neoadjuvant trials.

We demonstrate that optimal efficacy requires biomarker-guided patient selection integrating genetic and TME features, precise sequencing, and a mechanistic understanding of drug-specific immunomodulatory effects. The integration of platform trial designs (I-SPY2, CheckMate-7FL) with composite biomarker algorithms represents a paradigm shift toward precision neoadjuvant immunotherapy, offering a conceptual framework for transforming outcomes in molecularly defined HR+ breast cancer subsets.