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Abstract
Purpose: This retrospective cohort study aimed to determine whether adjuvant radiation therapy increases the risk of cardiac toxicity in Asian women with breast cancer, with a focus on patient-specific factors.

Methods and materials: We evaluated women who underwent primary breast surgery for breast cancer with (n = 520) or without (n = 774) adjuvant radiation therapy between January 2005 and May 2013. Patients who underwent breast surgery without radiation therapy were categorized as patients who received 0 Gy to the heart. The primary endpoint was the occurrence of a breast cancer treatment-related heart disease (BCT-HD), defined as a diagnosis of angina pectoris, unstable angina, myocardial infarction, ischemic heart disease, heart failure, or atrial fibrillation.

Results: In total, 1294 patients were included. The overall 5- and 10-year BCT-HD rates were 2.4% and 5.7%, respectively. The risk of an BCT-HD significantly increased per 1-Gy increase in the mean heart dose (adjusted hazard ratio: 1.23). Additionally, histories of hypertension (hazard ratio: 1.92), and diabetes (hazard ratio: 2.51) were found to be adverse risk factors, whereas regular physical exercise (hazard ratio: 0.17) was a protective factor. Subgroup analysis according to risk groups showed that the effect of increasing mean heart dose (per Gy) was similar between women without or with minimal risk factors (hazard ratio: 1.23) and women with multiple risk factors (hazard ratio: 1.27).

Conclusions: The results indicate a radiation dose-effect relationship for cardiac disease in breast cancer patients, highlighting that there remains a considerable risk of cardiac toxicity even with 3-dimensional radiation therapy planning. Thus, measures to minimize the heart dose in breast cancer patients undergoing adjuvant radiation therapy, even in those without any risk factor for cardiac disease, should be routinely implemented.

Affiliations

Seung Yeun Chung  1 , Jaewon Oh  2 , Jee Suk Chang  3 , Jaeyong Shin  4 , Kyung Hwan Kim  5 , Kyeong-Hyeon Chun  2 , Ki Chang Keum  5 , Chang-Ok Suh  6 , Seok-Min Kang  2 , Yong Bae Kim  5
1 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea; Department of Radiation Oncology, Ajou University School of Medicine, Suwon, South Korea.
2 Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
3 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: changjeesuk@yuhs.ac.
4 Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea.
5 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
6 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea; Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, South Korea.