Real-world insights into cardiometabolic comorbidities and their role in triple-negative breast cancer outcomes.

Abstract

e13157 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis. While the advent of chemo-immunotherapy, such as pembrolizumab with chemotherapy (Keynote-522 regimen), has improved outcomes, cardiometabolic comorbidities, including hypertension (HTN), diabetes mellitus (DM), obesity, dyslipidemia, and chronic kidney disease (CKD), remain underexplored as both predictors of outcomes and modifiable targets for intervention. This study evaluates their dual role, emphasizing opportunities to improve outcomes through personalized risk stratification and management. Methods: A retrospective analysis was conducted on 176 early-stage TNBC patients treated with the Keynote-522 regimen. Cardiometabolic comorbidities were defined as the presence of CKD, HTN, obesity (BMI > 30), DM, low high-density lipoprotein (HDL) levels ( < 50 mg/dL), or high triglycerides (TAGs) ( > 150 mg/dL). Pathological complete remission (pCR) and overall survival (OS) rates at 1 and 2 years were calculated. Kaplan-Meier curves with log-rank tests assessed survival differences, while Fisher’s exact and Wilcoxon rank-sum tests compared clinical variables between groups. Results: Of the 176 patients, 36 (20.5%) had cardiometabolic comorbidities. These patients were older (median age: 65.5 vs. 57 years, p < 0.005) and more likely to require dose reductions (41.7% vs. 24.3%, p < 0.005Although pCR rates were comparable between groups (52.8% vs. 52.1%, p < 0.005), CKD was associated with significantly lower pCR (22.5% vs. 8.7%, p < 0.005). OS was significantly worse in patients with cardiometabolic comorbidities, with 2-year OS rates of 79% compared to 99% in those without (p < 0.005). Subgroup analysis revealed significant associations between worse OS and HTN (p < 0.005, DM (p < 0.005), and obesity (P = 0.06, trending significance). Conclusions: Cardiometabolic comorbidities are key survival and treatment tolerability predictors in early-stage TNBC. Their role as modifiable risk factors offers actionable opportunities to enhance outcomes through tailored interventions and interdisciplinary care. Future research is needed to identify the underlying mechanisms and design targeted interventions to minimize the impact of cardiometabolic comorbidities on TNBC outcomes.