Abstract

Abstract Background: Trastuzumab (T) has improved patient (pt) outcomes in HER2+ breast cancer (BC) but carries a risk of cardiotoxicity. In the adjuvant setting, guidelines recommend cardiac monitoring (CM) every 3-4 months. In Ontario, Canada, pts with advanced BC (aBC) have CM every 6 months during HER targeted therapy, despite lack of evidence this practice improves patient outcomes. This study was conducted to understand predictive factors for cardiotoxicity and determine the impact of cardiovascular imaging in the HER2+ aBC population. Methods: This was a retrospective population-based cohort study of aBC pts treated with T (all lines), in Ontario (2007-17). Patient-level data was obtained using linked administrative databases through the Institute for Clinical Evaluative Sciences (ICES). The overall cohort was divided into two groups, those who developed a cardiac event and those who did not. In this study, a cardiac event (CE) was defined as new diagnosis of heart failure, cardiomyopathy or pulmonary edema between cycle 1 of T up to 90 days after final dose. Pts with pre-existing heart disease were excluded. Analysis included descriptive statistics for pt characteristics and logistic regression (LR) for factors predictive of CE. LR treated most patient characteristics as categorical values, including age in 10-year intervals (<40, 40-49, 50-59 etc.). Cycles of T were treated as a continuous variable. Results: Of the 2284 pts with HER2+ aBC treated with T, 167 (7.3%) developed a CE. Median age first dose T was 57 (IQR 49 - 66); 61 (IQR 51-70) for pts with CE. Median cycles T 16 (IQR 7-32); 21 (IQR 8-45) for pts with CE (p<0.01). Pertuzumab was co-administered in 25.0% of pts; 19.8% of pts with CE (p=0.102). Similar anthracycline exposure in the past 10 years was observed in pts without and with CE (74.1% vs. 71.9%, p=0.486). Overall, 86% of pts had at least one Echo/MUGA during T, a mean 2.26 (± 1.67) cardiac imaging tests per year. Pts with CE had more frequent cardiac monitoring (mean 3.22 ± 2.17 cardiac tests/year vs 2.18 ± 1.60 (p<0.01). 320 patients had no cardiac imaging at all (14%), only 4.1% (n=13) of those had CEs compared to 7.8% of pts who had cardiac imaging (154/1964). 12 (0.5%) pts died of cardiac causes, all had a CE. Using logistic regression, we found CEs were associated with age >60 (OR 5.21, 95% CI 1.83 -14.84, p=0.05) and higher number cycles of T (OR 1.01; 95% CI 1-101, p=0.0282). Conclusions: This is the first population-based study to report on cardiac events and cardiac monitoring in HER2 + aBC pts during T-based therapy. Older age and longer treatment with T were associated with increased risk of a CE. Most pts had CM in this cohort consistent with regional guidelines, however the group with no monitoring did not see increased rates of CEs. Future research should focus on evaluating the potential benefit of routine CM in aBC pts at greatest risk of experiencing a CE. Citation Format: Moira K Rushton-Marovac, Isac Lima, Meltem Tuna, Chiara Melloni, Kathy Pritchard, Steven Hawken, Susan F Dent. Cardiac monitoring in advanced breast cancer patients treated with trastuzumab: Does it improve cardiac safety? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-11.

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