Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer

Breast cancer is the most common malignant tumor among women worldwide. Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is the largest subgroup among these cases. The application of neoadjuvant chemotherapy (NACT) has rapidly increased in recent years, but its impact on long-term survival in HR+/HER2- breast cancer remains debated. This retrospective cohort study analyzed 21,299 stage II-III HR+/HER2- breast cancer patients from the SEER database (2010-2021), employing propensity score matching (PSM) to balance intergroup differences. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to identify significant prognostic factors. Among 21,299 patients, 17.8% received NACT. After propensity score matching (PSM; n = 6,930), the NACT group still showed poorer OS (5-year 83.7% vs. 89.6%; 10-year 69.9% vs. 76.7%; P < 0.001) and BCSS (85.9% vs. 91.6%; 10-year 75.3% vs. 81.8%; P < 0.001). Multivariate analysis confirmed NACT as an independent risk factor for mortality (HR 1.44, 95% CI 1.30-1.59, p < 0.001). Notably, achieving Pathological Complete Response (pCR) (17.3% of NACT patients) did not improve survival, while non-pCR patients had worse outcomes than adjuvant chemotherapy (ACT) recipients (OS HR 1.58, BCSS HR 1.68, p < 0.001). Stratified analyses revealed consistent survival disadvantages for NACT in stage IIB-IIIC, T1-T3, and N0-N2 subgroups. For stage III patients undergoing Breast-Conserving Surgery(BCS), NACT was associated with significantly lower OS and BCSS compared to ACT. NACT in stage II-III HR+/HER2- breast cancer is associated with inferior long-term survival outcomes compared to ACT, particularly in patients with T1-T3 tumors or N0-N2 lymph node involvement. While NACT may enhance BCS rates, its use should be cautiously weighed against potential survival trade-offs. These findings highlight the need for personalized treatment strategies and further validation through prospective trials, especially given the limitations of retrospective SEER data.