Is Neoadjuvant Chemotherapy Necessary in HR+/HER2–Breast Cancer? Real-World Experience

Abstract Background Hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) breast cancer (BC) is the most common subtype of invasive BC but demonstrates limited chemosensitivity. The role of neoadjuvant chemotherapy (NAC) in this population remains debated. This study aimed to evaluate clinicopathological characteristics, pathological response rates, and survival outcomes in HR+/HER2 − BC patients receiving NAC in a real-world setting. Methods We retrospectively analyzed 186 female patients with stage II–III HR+/HER2 − BC who underwent NAC followed by surgery between January 2015 and September 2024 at two tertiary centers in Türkiye. Clinicopathological variables, pathological complete response (pCR), partial pathological response (pPR), event-free survival (EFS), and overall survival (OS) were assessed. Predictors of pCR were identified using logistic regression; prognostic factors for EFS and OS were determined via Cox regression. Results Median follow-up was 30.6 months. Overall, 13.4% achieved pCR, while 42.5% had pPR, yielding a total pathological response (pR) rate of 55.9%. Independent predictors of pCR included grade 3 tumors (OR = 4.49; 95% CI: 1.74–11.63; p = 0.002) and estrogen receptor (ER) < 90% (OR = 2.64; 95% CI: 1.01–6.89; p = 0.047). The estimated 5-year EFS and OS rates were 77% and 88%, respectively. In multivariate analysis, ER ≥ 90% (EFS: HR = 2.70, p = 0.015; OS: HR = 3.16, p = 0.025) and pR (EFS: HR = 4.22, p = 0.011; OS: HR = 12.52, p < 0.001) were independent favorable prognostic factors. pCR alone was not significantly associated with survival. Conclusions In HR+/HER2 − BC, NAC yields modest pCR rates; however, any pathological tumor regression (pR) and high ER expression are associated with improved long-term outcomes. These findings suggest that pR, rather than pCR alone, may be a more clinically relevant endpoint in this subtype. Prospective studies are needed to optimize patient selection for NAC.