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

Abstract

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.

Keywords: adjuvant treatment; breast cancer; cardiotoxicity; electronic health records; frailty; geriatric oncology; outcomes; real-world data; risk factor; treatment; women's oncology.

Graphical abstract

Figure 1

Flowchart of Patient Selection In 2012 to 2022 electronic health records in the OneFlorida+ clinical research network, 4,630 female breast cancer patients received adjuvant treatments within 1 year after surgery. After applying exclusion criteria, a total of 2,025 patients were included in the final analysis. HCPCS = Healthcare Common Procedure Coding System; NDC = National Drug Code; RXCUI = RxNorm concept unique identifier.

Central Illustration

Cumulative incidence of Adverse CV Events by Frailty Solid lines represent cumulative incidences of adverse cardiovascular (CV) events for robust (green line), prefrail (orange line), and frail (red line) patients. The 2-year cumulative incidence rates of adverse CV events were 23.7% (95% CI: 20.6%-27.0%) for robust patients, 29.6% (95% CI: 24.9%-34.4%) for prefrail patients, and 42.6% (95% CI: 26.0%-58.3%) for frail patients. eFI = electronic health record frailty index; sHR = subdistribtution HR.

Figure 2

Restricted Cubic Splines Depicting Dose-Response Relationships Between eFI and Adverse Cardiovascular Events The electronic health record frailty index (eFI) represents the cumulative deficit eFI. The competing-risk model adjusts for age at diagnosis, race/ethnicity, insurance, census tract–level rurality, census tract–level poverty, baseline hypertension and diabetes status, and baseline health care utilization, year adjuvant therapy started, and adjuvant treatment regimen. The solid red line shows fitted values, with dashed black lines representing the 95% CIs. The green dotted line is the reference line, with eFI = 0.21 as the reference in the curve.