Body Mass Index Does Not Predict High Miller–Payne Response to Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: A Single-Center Retrospective Cohort Study of 647 Patients

Background: Neoadjuvant chemotherapy (NACT) response in breast cancer is primarily influenced by tumor biology; however, the independent role of host-related factors such as body mass index (BMI) remains unclear. This study evaluated clinicopathological predictors of a high Miller–Payne response after neoadjuvant chemotherapy in patients with stage II–III non-metastatic breast cancer, with particular focus on the role of body mass index. Methods: In this retrospective cohort study, 647 patients with stage II–III non-metastatic breast cancer treated with standard NACT between January 2010 and December 2020 at a single tertiary center were included. High pathological response was defined as Miller–Payne Grades 4–5. Clinical and tumor-related variables were analyzed, including age, menopausal status, body mass index, clinical stage, tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and Ki-67 proliferation index. Univariate and multivariable logistic regression analyses were performed to determine independent predictors of high pathological response. Results: A total of 647 patients were included (mean age: 49.18 ± 10.94 years; mean BMI: 28.45 ± 5.45 kg/m2), of whom 47.45% were postmenopausal. High Miller–Payne response (Grades 4–5) was observed in 40.96% of patients. High response was significantly associated with clinical stage (p = 0.034), tumor grade (p < 0.001), HER2 status (p < 0.001), ER status (p < 0.001), PR status (p < 0.001), and Ki-67 levels (p < 0.001). Median Ki-67 was higher in the high-response group (35.00% [IQR: 20.00–62.75] vs. 25.00% [IQR: 15.00–45.75], p < 0.001). No significant associations were observed for age (p = 0.299), BMI (p = 0.874), or menopausal status (p = 0.289). In multivariable analysis, HER2 positivity (adjusted OR = 3.71, 95% CI: 2.23–6.20, p < 0.001) and Ki-67 (adjusted OR = 1.01 per 1% increase, 95% CI: 1.00–1.02, p = 0.009) were independently associated with high response, whereas ER positivity (adjusted OR = 0.50, 95% CI: 0.25–0.98, p = 0.043) and postmenopausal status (adjusted OR = 0.37, 95% CI: 0.17–0.81, p = 0.013) were inversely associated. BMI was not independently associated with response (p = 0.964). Conclusions: Response to neoadjuvant chemotherapy appears to be mainly determined by tumor biology, particularly receptor status and proliferative activity, rather than anthropometric measures such as body mass index.