The Impact of Metabolic Syndrome on Pathological Complete Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Prospective Observational Study

Abstract Metabolic syndrome (MetS) notably influences breast cancer pathogenesis, treatment efficacy, and prognosis. This study investigates the association between MetS and the rate of pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer (LABC). To study the response of NACT in patients with LABC with or without MetS. In this prospective observational study (June 2022–June 2024), 188 patients with LABC planned for NACT were enrolled. Participants were stratified into two cohorts based on the NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) Criteria: Arm A (MetS, n = 91) and Arm B (non-MetS, n = 97). The primary outcome was the achievement of pCR. Associations were analyzed using chi-square tests, with univariate and multivariate analyses to identify predictive factors. The overall pCR rate was 20.2% (n = 38/188). A lower, though not statistically significant, pCR rate was observed in the MetS group (15.4%, n = 14/91) compared with the non-MetS group (24.7%, n = 24/97) (p = 0.078). Subgroup analyses revealed significant interactions: HER2-negative patients with MetS had a significantly lower pCR rate than their non-MetS counterparts (p = 0.049). Furthermore, premenopausal women without MetS achieved significantly higher pCR rates than premenopausal women with MetS (p = 0.008). On multivariate analysis adjusting for age and menopausal status, MetS was not an independent predictor of pCR (odds ratio: 0.65, 95% confidence interval: 0.30–1.39, p = 0.27). ER and HER2 status alone did not show a significant independent association with pCR. The presence of MetS may be associated with a reduced likelihood of achieving pCR after NACT in patients with LABC, with this effect appearing most pronounced in HER2-negative and premenopausal subgroups. These findings highlight MetS as a critical host factor influencing treatment outcomes and underscore the need for integrated metabolic management in breast cancer care.