Abstract
Hormone receptor-positive, HER2-negative breast cancer represents a significant subset of patients who often exhibit suboptimal responses to neoadjuvant chemotherapy (NACT). Identifying strategies to enhance chemosensitivity in this population is a clinical priority. In this study, we investigated the potential contribution of statin therapy to the efficacy of NACT. We retrospectively analyzed 60 patients treated between 2014 and 2025, comprising 22 statin users and 38 non-users. While the overall cohort analysis did not demonstrate a statistically significant difference in pCR rates, an exploratory postmenopausal subgroup analysis (performed because all statin users were postmenopausal) showed a higher pCR rate among statin users; this finding is hypothesis-generating and should be interpreted cautiously (31.8 vs. 5.0%, p = 0.047). In an exploratory multivariable logistic regression analysis limited by sparse events in the postmenopausal subgroup, statin use was associated with pCR after adjustment for Ki-67 proliferation index and clinical T stage; however, the estimate was imprecise and should be interpreted cautiously. Although pCR is not a validated surrogate for long-term survival in this specific subtype, our findings suggest that statins may biologically enhance short-term chemosensitivity, potentially through mevalonate pathway inhibition and modulation of the tumor microenvironment. These preliminary results support the need for larger prospective studies to further elucidate the role of statins as adjunctive agents in breast cancer management.