Retrospective study of impact of cardiometabolic health on chemo-immunotherapy treatment outcomes in early-stage triple-negative breast cancer

Triple-negative breast cancer (TNBC) lacks effective targeted therapies, and pivotal trials of pembrolizumab with neoadjuvant chemotherapy (KEYNOTE-522) underrepresent patients with cardiometabolic comorbidities. A retrospective study at the Cleveland Clinic (Cleveland, OH) evaluated the impact of cardiometabolic health on outcomes with the KEYNOTE-522 regimen among early-stage TNBC patients. Between January 2020 and April 2025, 222 patients with early-stage TNBC were treated. Among these patients, 55 (24.8%) met the AHA criteria for metabolic syndrome. Patients with metabolic syndrome were older (median 65 versus 55 years; p=0.004) and more frequently Black (43.6% versus 18.0%) and had more cardiometabolic comorbidities including obesity, diabetes, hypertension, chronic kidney disease, low HDL cholesterol, and elevated triglycerides. Dose reductions were more frequent among patients with metabolic syndrome (32.7% versus 20.4%). Pathologic complete response rates did not differ significantly between patients with versus without metabolic syndrome (72.7% versus 68.9%; p=0.62). With median follow-up of 28.8 months, metabolic syndrome was associated with worse overall survival (p=0.0013). Chronic kidney disease, hypertension, and diabetes, but not obesity, were independent predictors of mortality. The authors conclude that cardiometabolic comorbidities were associated with poorer survival and greater treatment intolerance despite preserved pCR.