HEART (Heart Evaluation After Radiation Therapy): Novel Detection of Cardiotoxicity in Breast Cancer Patients

Abstract

Sensitive and reliable tools for the detection and quantification of subclinical cardiotoxicity are critical following RT for primary breast cancer. We prospectively evaluated the association between breast RT and several contemporary measures of cardiac and global cardiovascular function, including cardiopulmonary exercise testing (CPET), in a uniformly-treated cohort with locally-advanced breast cancer. Sixteen patients with HER-2 negative, stage II or III breast cancer were enrolled following completion of neoadjuvant dose-dense anthracycline-containing chemotherapy and mastectomy with immediate reconstruction. Two pre-defined cohorts were analyzed: (1) patients receiving multi-beam IMRT to 50Gy to the reconstructed chest wall and regional nodes (RT) and (2) control group that did not receive RT (No RT). Study assessments were: (1) echocardiogram with speckle tracking (strain), 2) endothelial function - flow-mediated dilatation by brachial artery, (3) CPET, (4) cardiac biomarkers, and 5) Functional Assessment of Cancer Therapy-Breast (FACT-B) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaires. Study assessments were performed at baseline (0-4 weeks prior to RT or 4-8 weeks after mastectomy) and follow-up (2-4 weeks post RT or 15-20 weeks after mastectomy). Differences between baseline and follow-up measurements were assessed using the t-test and the Wilcoxon signed-rank test. A total of 11 patients (9 RT, 2 No RT) had complete data sets and were evaluable for the primary endpoints. Median age was 46 yrs (range: 30-63 yrs). In the RT group, median mean heart dose was 4.66 Gy (3.95 Gy for 5 right-sided and 7.73 Gy for 4 left-sided breast plans). For the entire cohort, there were no significant differences in the mean values between baseline and follow-up ejection fraction (61% vs 63%; p=.07), global longitudinal strain (-19.6 vs -20.0; p=.23), FACT-B scores (111 vs 115; p=.67), and FACIT-Fatigue scores (40 vs 38, p=.40). In the RT group, the mean baseline VO2peak and percent age-predicted VO2peak were significantly higher at follow-up (23.8 vs 25.8, p=.03) (89.5% vs 96.2%; p=.03). Results for cardiac biomarkers and flow-mediated dilatation will be reported at the time of presentation. In this signal-seeking study, breast RT was not associated with detrimental changes in any parameter. Conversely, VO2peak significantly increased from pre- to post-RT. These findings require validation of CPET as a predictor of cardiotoxicity after breast RT in a larger cohort.