Risk of Heart Failure after Radiotherapy in Women with HER2+ Breast Cancer Treated with Trastuzumab

Abstract

We conducted a case-cohort study to analyze the effect of heart exposure to ionizing radiation on the subsequent risk of heart failure (HF) in women with human epidermal growth factor receptor 2 (HER2+) breast cancer treated with trastuzumab and radiation therapy (RT). Between 2000 and 2015, 731 patients were treated with trastuzumab at our institution for HER2+ breast cancer, among whom 480 had documentation of left ventricular ejection fraction (LVEF) before and after starting treatment. Males (n=40) and patients with a clinical diagnosis of HF or LVEF≤53 prior to trastuzumab initiation (n=32) were excluded. Of the 408 remaining patients, 252 received adjuvant breast/chest wall photon RT, median dose of 5000cGy in 25 fractions. 65 of the 252 had CT-based treatment planning cardiac dosimetry accessible for analysis, including 15 women with clinically diagnosed HF and 50 controls. 6 patients in the control group and 2 patients in the HF group also received nodal RT. The overall median mean heart dose was 223.8 cGy (range, 15.9 to 1579.4 cGy). Baseline EF was the only factor associated with a higher rate of HF (table 1). The heart mean, maximum, V500cGy, and V2000cGy were not associated with higher rates of HR, nor did other clinical factors such as anthracycline therapy, obesity, age, or hypertension. Mean and maximum dose delivered to heart was comparable between the two groups. Exposure of the heart to radiation during RT for breast cancer did not significantly increase the rate of heart failure. Further investigation into predictors of HF in patients receiving trastuzumab is needed to optimize surveillance and preventative strategies.Abstract 2089; Table 1CriteriaNo heart failure (n=50)Heart failure (n=15)Total (n=65)p valueAnthracycline use (%, n)80% (n=40)60% (n=9)75% (n=49)0.17EF prior to trastuzumab therapy (median, range)64 (53-76)61 (55-68)63 (53-76)0.01Radiation to both chest walls (%, n)6% (n=3)13.3% (n=2)7.7% (n=5)0.33Radiation to left chest wall (%, n)68% (n=34)40% (n=6)61.5% (n=40)0.07Radiation to right chest wall (%, n)26% (n=13)46.7% (n=7)30.8% (n=20)0.20Mean dose of radiation to heart (median (cGY), range)245.6 (32.2-1264.5)206.8 (15.9-1579.4)223.8 (15.9-1579.4)0.70Max dose of radiation to heart (median (cGY), range)3219.8 (256-5928.7)3454.1 (145.2-5231.8)3287 (145.2-5928.7)0.57Heart v_500 (median (cc), range)41.7 (0-521.2)37.1 (0-411.8)38.2 (0-521.2)0.80Heart v_2000 (median (cc), range)2.5 (0-119)2.1 (0-118.5)2.5 (0-119)0.59 Open table in a new tab