Impact of Pre-Existing Frailty on Cardiotoxicity Among Breast Cancer Patients Receiving Adjuvant Therapy

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BACKGROUND: Prior research suggests that breast cancer patients with a high burden of frailty may face an increased risk of cardiotoxicity. OBJECTIVES: This study sought to examine the association between frailty and cardiotoxicity rates in female breast cancer patients receiving adjuvant therapy after surgery. METHODS: We analyzed data from the OneFlorida+ clinical research network, focusing on breast cancer patients treated with adjuvant chemotherapy and targeted therapy from 2012 to 2022. Cardiovascular rates during adjuvant treatments were calculated based on pre-existing frailty, measured using the cumulative deficit frailty index (electronic health record frailty index). We employed multivariable Gray's method to examine the association between frailty with cardiotoxicity. RESULTS: The final cohort included 2,050 patients (mean age 50.6 years), with 415 (20.2%) experiencing nonfatal adverse cardiovascular events after adjuvant therapy. The incidence of adverse cardiovascular events was 17.8% in robust, 23.2% in prefrail, and 29.4% in frail patients. In multivariable analysis, prefrail (adjusted subdistribution HR [sHR]: 1.35; 95% CI: 1.06-1.71; P = 0.015) and frail (adjusted sHR: 1.70; 95% CI: 1.11-2.61; P = 0.015) patients had a higher likelihood of experiencing adverse cardiovascular events compared with robust patients. Among non-Hispanic White and Black patients, prefrail (adjusted sHR: 1.48; 95% CI: 1.04-2.11; P = 0.031; and adjusted sHR: 1.59; 95% CI: 1.06-2.37; P = 0.024, respectively) and frail (adjusted sHR: 1.96; 95% CI: 1.10-3.50; P = 0.022; and adjusted sHR: 2.13; 95% CI: 1.11-4.10; P = 0.023, respectively) patients were more likely to experience adverse cardiovascular events compared with robust patients. No significant differences were observed in other racial/ethnic groups. CONCLUSIONS: These findings highlight the need for close monitoring of cardiotoxicity in frail breast cancer patients undergoing adjuvant treatments to improve cardiovascular risk management.

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