Survival benefit of neoadjuvant chemotherapy in HR+/HER2− early breast cancer stratified by luminal B status and clinical risk: a real-world cohort study in a Chinese population

Background: The role of neoadjuvant chemotherapy (NACT) in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer remains controversial. This real-world study evaluated the impact of NACT on overall survival (OS) and disease-free survival (DFS), specifically focusing on differential benefits within Luminal B and high-risk Luminal B subgroups. Methods: We retrospectively analyzed 990 patients with HR+/HER2- invasive breast cancer treated between 2013 and 2022. Patients received either NACT (n=195) or upfront surgery (n=795). "High-risk Luminal B" was defined as Luminal B subtype combined with clinical T3, N2, or Ki-67 ≥30%. Multivariable Cox regression adjusted for confounders to assess prognostic factors. Interaction tests evaluated heterogeneity in treatment effects across subgroups. Results: Despite higher baseline risk in the NACT group (larger tumors, higher grade), NACT was independently associated with better OS (HR 0.60, 95% CI 0.37-0.99) and DFS (HR 0.61, 95% CI 0.42-0.90) in the overall population. This benefit was most pronounced in the Luminal B subgroup (OS HR 0.47, 95% CI 0.26-0.84). A significant interaction was observed between treatment and risk status for OS (P for interaction = 0.026). Specifically, high-risk Luminal B patients achieved significantly higher 5-year OS with NACT (91.5% vs. 80.9%), whereas non-high-risk patients derived no survival benefit (adjusted HR 1.30). DFS showed consistent numerical trends but lacked significant interaction. Conclusion: NACT provided a survival advantage in this real-world HR+/HER2- cohort, with benefits primarily concentrated in high-risk Luminal B patients characterized by aggressive biology and high tumor burden. These findings support a risk-adapted strategy prioritizing NACT for this high-risk population while suggesting caution for lower-risk subgroups.