Abstract PO3-09-02: Identifying risk factors for trastuzumab-induced cardiotoxicity among multi-ethnic women with HER2-positive early-stage breast cancer

Abstract Introduction: While trastuzumab, a HER2-targeted therapy for patients with HER2-positive breast cancer, has been shown to improve disease-free and overall survival rates, it also confers the risk of significant morbidity in the way of trastuzumab-induced cardiotoxicity (TIC). TIC may present as asymptomatic decline in left ventricular ejection fraction (LVEF) or as symptomatic heart failure. Given that racial/ethnic minorities are at higher risk for cardiovascular disease (CVD) compared to non-Hispanic Whites, our objective was to assess racial/ethnic differences in TIC and LVEF recovery among multi-ethnic patients with HER2-positive early-stage breast cancer. Methods: We conducted a retrospective cohort study including patients diagnosed with stage I-III HER2-positive breast cancer between 2007-2022 who had received adjuvant trastuzumab therapy at Columbia University Irving Medical Center (CUIMC) in New York, NY. TIC was defined as 10% decrease in LVEF to an overall LVEF 50% and was confirmed by a minimum of two serial echocardiograms, whereas LVEF recovery was defined as a return to a LVEF 50%. Descriptive statistics, univariate and multivariate logistic regression analyses were conducted to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between sociodemographic factors, tumor characteristics, treatment regimens, and CVD risk factors with the main outcome of TIC. Results: In the final cohort (N=500), median age was 53 years (IQR: 45.0-62.0) with 36.6% non-Hispanic White (NHW), 15.8% non-Hispanic Black (NHB), 27.8% Hispanic, and 19.8% Asian/Pacific Islander/Other. About 68.2% of patients received adjuvant radiation therapy, 30.2% were treated with anthracyclines, 37.8% with pertuzumab, 4.6% with T-DM1 and 69.0% with endocrine therapy. Fifty-three (10.6%) patients developed TIC, half of which experienced LVEF recovery. Compared to NHW, NHB patients had a higher rate of TIC (9.3% vs. 17.7%, respectively) and lower rate of LVEF recovery (70.6% vs. 21.4 % in those with TIC, respectively). On multivariable analysis, increasing age, lower LVEF at baseline, anthracycline exposure, and coronary artery disease (CAD) were associated with TIC (see Table). We found no association between TIC and use of pertuzumab or T-DM1. Discussion: In our racially/ethnically diverse study population, we found an incidence of TIC comparable to previous clinical studies. NHB patients had double the incidence of TIC and a lower incidence of LVEF recovery when compared to NHW patients. Given the observed racial disparities in TIC and LVEF recovery, NHB patients may require closer cardiac monitoring and restricted use of anthracyclines with adjuvant trastuzumab treatment. More research on cardiotoxicity associated with newer forms of HER2-targeted therapies is necessary. Table: Multivariable logistic regression model with outcome of TIC Citation Format: Leila Mishalani, Anna Vaynrub, Katherine Crew. Identifying risk factors for trastuzumab-induced cardiotoxicity among multi-ethnic women with HER2-positive early-stage breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-02.