Association between body mass index and efficacy of neoadjuvant targeted therapy in HER2-positive breast cancer in a Chinese multicenter cohort

Overweight/Obesity, characterized by body mass index (BMI) ≥ 25 kg/m², is recognized as a significant prognostic factor in HER2-positive breast cancer, yet its precise influence on neoadjuvant targeted therapy response remains incompletely understood. To address this critical knowledge gap, we conducted a multicentre retrospective cohort study investigating the impact of BMI on pathological complete response (pCR) among HER2-positive breast cancer patients undergoing neoadjuvant targeted therapy. The study comprised 826 Chinese patients from January 2013 to June 2024. Patients were stratified into into two cohorts: underweight/normal weight (UW/NW: BMI < 25 kg/m²) and overweight/obese (OW/OB: BMI ≥ 25 kg/m²). Our analysis revealed a statistically significant disparity in pCR rates, with OW/OB patients demonstrating markedly lower response rates compared to UW/NW patients (36.87% vs. 44.56%; adjusted odds ratio 0.71, 95% CI 0.51-0.99; p = 0.025). Sophisticated restricted cubic spline (RCS) analysis uncovered a nuanced non-linear negative correlation between BMI and pCR rate. Exploratory subgroup analysis further elucidated that OW/OB patients, particularly those aged > 50 years, postmenopausal, with lymph node involvement, hormone receptor negativity, or HER2 3 + status, exhibited substantially compromised pCR rates. Collectively, these findings substantiate the potential of BMI as a robust predictive biomarker for neoadjuvant therapy response in Chinese HER2-positive breast cancer patients.