The Risk of Cardiac Disease in Asian Breast Cancer Patients: Impact of Patient-Specific Factors and Heart Dose Based on Individual Heart Dose Calculation from Three-Dimensional RT Planning

Abstract

Adjuvant radiation therapy (RT) increases the risk of cardiac disease in breast cancer survivors. In comparison, exercise and healthy lifestyle choices are known to be cardioprotective in the general population. However, the impact of patient-specific factors on the interaction between cardiac risk and RT has not been studied well, as we have raised this issue recently (IJORBP 2018;100;1298-1299). The purpose of this study was to analyze whether adjuvant RT increases the risk of cardiac toxicity in Asian breast cancer women and whether patient-specific factors would actually affect the risk of RT-related cardiac toxicity. A total of 1294 women who received primary surgery for breast cancer (520 with adjuvant RT, 774 without adjuvant RT) from 01/2005 to 05/2013 were included for analysis. As for mean heart dose (MHD), all patient’s contours and dose distributions in every RT session were transferred and integrated to a deformable registration algorithm software to display individual three-dimensional computed tomography planning data for each patient. Major coronary event (MCE) was defined as a diagnosis of myocardial infarction, coronary revascularization, or death resulting from ischemic heart disease. The median age and body mass index was 50 years (range, 24–87 years) and 22.9 kg/m2 (range, 14.6-35.9 kg/m2), respectively. Hypertension (HTN), diabetes (DM), cardiac disease, and smoking rates were 23.2%, 6.5%, 2.0%, and 2.2%, respectively. A total of 188 (14.5%) patients reported performing exercise regularly. The median MHD were 3.4 Gy (range, 0.0–14.2 Gy) overall, 1.53 Gy for those with tumors in the right breast, 5.22 Gy for those with tumors in the left breast without internal mammary node (IMN) irradiation, and 6.97 Gy for those with tumors in the left breast with IMN irradiation. Median follow-up period was 78.6 months (range, 60.0-153.7 months). The 5- and 10-year MCE rates were 2.3% and 3.9%, respectively. As MHD increased per 1 Gy, the risk of MCE significantly increased with an adjusted hazard ratio (HR) of 1.21 (HR 1.21, 95% confidence interval [CI] 1.12–1.31; P <.001). Additionally, history of HTN (HR 2.07, CI 1.01–4.25; P =.047) and DM (HR 3.43, CI 1.53–7.70; P =.003) were found to be adverse risk factors, whereas regular exercise (HR 0.20, CI 0.05–0.86; P =.030) was a protective factor. In a subgroup analysis, the impact size of increasing MHD (per Gy) for MCE was similar in patients without or minimal risk factor (HR 1.17, CI 1.03–1.33; P =.013), as compared to patients with multiple risk factors (HR 1.18, CI 1.08–1.31; P =.001). This is the first study in Asia and third study overall to report a radiation dose-effect relationship for cardiac disease in breast cancer patients. It is time to apprehend that the risk of cardiac disease after modern radiotherapy is not overblown and adopt technical approaches to minimize heart dose in breast cancer patients undergoing adjuvant RT, even in those without any risk factor for cardiac disease.