Original article Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer Elisa K. Chan a , Ryan Woods b , Sean Virani c , Caroline Speers d , Elaine S. Wai e , Alan Nichol f , Mary L. McBride b , Scott Tyldesley f,⇑ a Department of Oncology, Saint John Regional Hospital; b BC Cancer Agency, Cancer Control Research Department, Vancouver; c Division of Cardiology, University of British Columbia, Vancouver; d BC Cancer Agency, Breast Cancer Outcomes Unit, Vancouver; e BC Cancer Agency, Radiation Therapy Program, Victoria; and f BC Cancer Agency, Radiation Therapy Program, Vancouver, Canada article info Article history: Received 31 July 2013 Received in revised form 2 July 2014 Accepted 22 August 2014 Available online xxxx Keywords: Hypofractionation Cardiac mortality Breast cancer abstract Background and purpose: Ongoing concern remains regarding cardiac injury with hypofractionated whole breast/chest-wall radiotherapy (HF-WBI) compared to conventional radiotherapy (CF-WBI) in left-sided breast cancer patients. The purpose was to determine if cardiac mortality increases with HF-WBI relative to CF-WBI. Materials and methods: Between 1990 and 1998, 5334 women with early-stage breast cancer received post-operative radiotherapy to the breast/chest wall alone. A population-based database recorded base- line patient, tumor and treatment factors. Baseline cardiovascular risk factors were identified from hos- pital administrative records. A propensity-score model balanced risk factors between radiotherapy groups. Cause of death was coded as breast cancer, cardiac or other cause. Cumulative mortality from each cause after radiotherapy was estimated using a competing risk approach. Results: For left-sided cases, median follow-up was 14.2 years. 485 women received CF-WBI, 2221 women received HF-WBI. There was no difference in 15-year mortality from cardiac causes: 4.8% with HF-WBI and 4.2% with CF-WBI (p = 0.74), even after propensity-score adjustment (p = 0.45). There was no difference in breast cancer mortality or other cause mortality. For right-sided cases, there was no dif- ference in mortality for the three causes of death. Conclusions: At 15-years follow-up, cardiac mortality is not statistically different among left-sided breast cancer patients treated with HF-WBI or CF-WBI. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2014) xxx–xxx The risk of long-term cardiac injury from whole breast radiother- apy for early-stage breast cancer after breast-conserving surgery remains a topical issue [1]. The Early Breast Cancer Trialists’ Collab- orative Group studied the long-term side-effects of radiotherapy and found an increased risk of mortality from heart disease among patients receiving radiotherapy [2]. Older studies have suggested that left-sided breast radiotherapy is associated with greater mor- tality from cardiac causes compared to right-sided radiotherapy [3,4]. However, newer studies using population-based data con- cluded that there was no difference in mortality due to ischemic heart disease or other cardiac causes among women treated for left or right-sided breast cancer with conventional fractionated whole breast radiotherapy (CF-WBI) [5]. Population-based data using Surveillance, Epidemiology and End-Results (SEER)-Medicare also found no difference in mortality with left vs. right-sided cases in women treated after 1982 [6]. As a result of randomized trials, hypofractionated whole breast radiotherapy (HF-WBI) has become an established alternative to CF-WBI, showing equivalent long-term local control and overall survival for women with early-stage breast cancer after breast con- serving surgery [7–9]. One of these trials reported no difference in 10-year cardiac mortality [7]. In the HF-WBI arm, 12 deaths were due to cardiac causes, compared to 9 deaths in the CF-WBI arm. However, the 2011 ASTRO guidelines regarding fractionation for whole breast irradiation recommends that when the heart is in the radiotherapy field, HF-WBI should be avoided ‘due to lingering uncertainty regarding late effects of HF-WBI on cardiac function’ [10]. The British Columbia Cancer Agency (BCCA) has a longstanding history of using HF-WBI for early-stage breast cancer after breast http://dx.doi.org/10.1016/j.radonc.2014.08.021 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author. Address: 600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada. E-mail address: styldesl@bccancer.bc.ca (S. Tyldesley). Radiotherapy and Oncology xxx (2014) xxx–xxx Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com Please cite this article in press as: Chan EK et al. Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer . Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.08.021