Late Cardiac Mortality and Morbidity in Early-Stage Breast Cancer Patients After Breast-Conservation Treatment Eleanor E.R. Harris, Candace Correa, Wei-Ting Hwang, Jessica Liao, Harold I. Litt, Victor A. Ferrari, and Lawrence J. Solin A B S T R A C T Purpose Several studies have reported increased cardiac mortality related to the use of left-sided breast or chest-wall irradiation. This study was undertaken as a comprehensive examination of the long-term cardiac mortality and morbidity after breast irradiation using contemporary irradiation techniques. Methods The medical records of 961 consecutive patients presenting between 1977 and 1994 with stage I or II breast cancer treated with breast conservation treatment were reviewed. Data was recorded on baseline pretreatment patient, tumor and treatment characteristics and on subsequent cancer or cardiac related events. The median follow-up time was 12 years. Results There was no difference in overall mortality from any cardiac cause (P = .25). Death from any cardiac cause occurred in 2% of right-sided patients and 3.5% of left-sided patients. However, in the second decade after treatment, there was a higher rate of cardiac deaths in left-sided patients, with a cumulative risk of 6.4% (95% CI, 3.5% to 11.5%) for left-sided compared with 3.6% (95% CI, 1.8% to 7.2%) for right-sided patients at 20 years. There were statistically higher rates of chest pain, coronary artery disease, and myocardial infarction diagnosed in left-sided patients (all P  .002). The presence of hypertension was associated with a higher risk of coronary artery disease in left-sided patients. Conclusion Irradiation to the left breast is not associated with a higher risk of cardiac death up to 20 years after treatment, but is associated with an increased rate of diagnoses of coronary artery disease and myocardial infarction compared with right breast treatment. J Clin Oncol 24:4100-4106. © 2006 by American Society of Clinical Oncology INTRODUCTION A number of randomized trials comparing breast- conservation therapy, including lumpectomy and breast irradiation, with mastectomy have demon- strated equivalent survival outcomes between these two treatment modalities for women with early-stage breast cancer. 1-3 Several studies have raised concerns that cardiac morbidity and mor- tality may be increased by the use of left-sided breast or chest wall irradiation, which often in- cludes some of the myocardium and coronary arteries. 4-8 Many such studies used irradiation techniques that exposed larger volumes of heart to greater doses than current treatment standards, such as anterior photon beams and treatment with cobalt-60 or orthovoltage therapy. During the last two decades, megavoltage lin- ear accelerator– based therapy to tangential fields has resulted in a lower volume of heart exposed to radiation in left-sided patients. Such techniques have been employed at the University of Pennsyl- vania (Philadelphia, PA) since 1977, with infre- quent prophylactic treatment of the internal mammary nodes. This study was therefore under- taken to perform a comprehensive examination of the long-term sequelae to the heart and coro- nary vessels after left-sided irradiation compared with right-sided treatment using contemporary irradiation techniques. Cardiac morbidity and mortality as well as potential contributing medi- cal and therapeutic factors were examined to de- termine the long-term risk of cardiac damage in early-stage breast cancer patients. From the Department of Radiation Oncology; Department of Biostatistics and Epidemiology; Cardiovascular Imag- ing Section, Department of Radiology; and Division of Cardiovascular Medi- cine, Department of Medicine, Univer- sity of Pennsylvania School of Medicine, Philadelphia, PA. Submitted November 25, 2005; accepted June 8, 2006; published online ahead of print at www.jco.org on August 14, 2006. Supported in part by US Army Medical Research and Material Command under DAMD17-03-1-0309 (E.E.R.H., J.L.) and Breast Cancer Research Foundation (E.E.R.H., W.-T.H., L.J.S.). These fund- ing sources had no role in the collec- tion, analysis, interpretation or reporting of the data presented, or in the deci- sion to submit the data for publication. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Address reprint requests to Eleanor E.R. Harris, MD, Moffitt Cancer Center and Research Institute, Division of Radi- ation Oncology, 12902 Magnolia Dr, Tampa, FL 33612; e-mail: HarrisE@moffitt.usf.edu. © 2006 by American Society of Clinical Oncology 0732-183X/06/2425-4100/$20.00 DOI: 10.1200/JCO.2005.05.1037 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 24  NUMBER 25  SEPTEMBER 1 2006 4100 Downloaded from jco.ascopubs.org on March 4, 2016. For personal use only. No other uses without permission. Copyright © 2006 American Society of Clinical Oncology. All rights reserved.