Abstract P6-12-17: Identifying risk factors and effect modifiers of trastuzumab-induced cardiotoxicity among multi-ethnic women with early-stage HER2-positive breast cancer
Authors: Yuan A , Topkara V , Hershman DL , Kalinsky K , Accordino MK , Trivedi MS , Yu A , Genkinger JM , Crew KD 
Published: February 2018

Introduction: Trastuzumab-based adjuvant therapy is the current standard of care for early-stage HER2-positive breast cancer. However, trastuzumab has also been associated with an increased risk of cardiotoxicity, especially when given following an anthracycline. Trastuzumab-induced cardiotoxicity (TIC) can present as asymptomatic left ventricular ejection fraction (LVEF) decline or symptomatic heart failure. Our objective was to identify predictors of TIC among multi-ethnic patients with early-stage HER2-positive breast cancer. Unlike prior observational studies, our study included a high representation of racial/ethnic minorities, who are at increased risk of cardiovascular disease (CVD) compared to non-Hispanic whites.

Methods: We conducted a retrospective cohort study in patients with stage I-III HER2-positive breast cancer, diagnosed from 2007 to 2015 at Columbia University Medical Center (CUMC) in New York, NY, who had received adjuvant trastuzumab therapy. Participants had at least two serial echocardiograms or MUGA scans to assess TIC, which was defined as at least a 10% decrease in LVEF from baseline or LVEF &lt;50%. LVEF recovery was defined as at least a 10% increase in LVEF or LVEF &gt;50%. We conducted descriptive statistics and univariate and multivariable logistic regression to estimate the associations between socio-demographic factors, breast tumor and treatment characteristics, and CVD risk factors (including smoking status, body mass index [BMI], hypertension, diabetes, hyperlipidemia, coronary artery disease) and TIC. Interactions between race/ethnicity and CVD risk factors were assessed using a logistic regression model.

Results: In our study population (N=279), the mean age was 52.7 years (standard deviation, 12.1) with 36.6% non-Hispanic white, 18.3% non-Hispanic black, 34.8% Hispanic, and 10.4% Asian patients. There were no differences by race/ethnicity in tumor and treatment characteristics (over half had prior anthracyclines), but racial/ethnic minorities had higher BMI and were more likely to have hypertension compared to non-Hispanic whites. About a third of patients developed TIC and 14.7% had an LVEF decline to &lt;50%, of which 15 (16.1%) experienced LVEF recovery. In multivariable analysis, prior anthracycline use and hypertension were significantly associated with increased odds of developing TIC (odds ratio [OR]: 2.25, 95% confidence interval [CI]: 1.25, 4.06; OR: 2.13, 95% CI: 1.15, 3.93, respectively). There was a significant interaction (p=0.027) between race/ethnicity and hypertension on odds of developing TIC with hypertensive non-Hispanic white patients experiencing 6.05 (95% CI: 2.19, 16.75) times the odds of developing TIC compared to non-hypertensive non-Hispanic whites.

Discussion: We observed a higher incidence of TIC and lower incidence of LVEF recovery compared to previous clinical trials. Given patient selection for clinical trials, our results may be more representative of clinical practice settings. We found a particularly high risk among non-Hispanic white patients with hypertension. Patients with hypertension may require closer blood pressure monitoring and treatment with anti-hypertensives in order to reduce risk of developing cardiotoxicity.

Citation Format: Yuan A, Topkara V, Hershman DL, Kalinsky K, Accordino MK, Trivedi MS, Yu A, Genkinger JM, Crew KD. Identifying risk factors and effect modifiers of trastuzumab-induced cardiotoxicity among multi-ethnic women with early-stage HER2-positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-17.