Darby and colleagues are to be congratulated for an ambitious population-based case-control study that demonstrates the impact of postoperative adjuvant ionizing radiation for early-stage breast cancer on ischemic heart disease.1 The study examined roughly 1,000 cases and 1,000 controls in Sweden and Denmark from 1958 to 2001.
Data in Context
Their work must be taken in the context of more recent cohorts that have been treated with improved planning techniques that reduce the volume of cardiac tissue exposed and dose delivered to the heart.2,3 Patt and colleagues reported no significant differences in cardiac morbidity for right- vs left-sided radiotherapy in a larger and more contemporary series of approximately 16,000 patients.2 In a study by Giordano and colleagues (N = 27,000), death from ischemic heart disease was greater in patients with left-sided tumors who were diagnosed in the earliest time period (1973–1979) as opposed to later time periods.3 Consistent with the notion that time and technique matter, the highest proportional increase in major cardiac events observed in the Darby et al study indeed occurred in the 1970s, although the subset analyses are underpowered to show statistical significance.
In a recent report by Chung, Pierce, and colleagues from the University of Michigan Department of Radiation Oncology, serial adenosine stress myocardial perfusion single-photon emission computed tomography (SPECT-CT) scans were employed to assess perfusion defects, ejection fraction, and wall motion abnormalities before and 1 year after left-sided adjuvant radiation.4 The use of three-dimensional conformal radiation therapy or intensity-modulated radiation therapy resulted in low heart doses, with only 3 of 32 patients receiving a mean heart dose greater than 5 Gy (mean dose to heart = 2.82 Gy, range = 1.11–6.06 Gy). Despite the fact that 30 of the 32 subjects received adjuvant anthracycline, there were no significant differences in these very sensitive metrics of cardiac function before vs after radiotherapy.
Similarly, in a more contemporary series (N = 1,500), there was no difference in cardiac events among women receiving both an anthracycline and trastuzumab (Herceptin) in NCCTG N9831 as a function of laterality of adjuvant radiotherapy.5
Few would argue with the notion that baseline risk factors influence the risk of radiotherapy-related cardiotoxicity. Nevertheless, with longer follow-up on the more recent large studies, even in the context of potentially cardiotoxic systemic therapies such as anthracyclines and trastuzumab, there is reason to be optimistic that modern and meticulous radiation planning will minimize, though not likely eliminate, what has historically been a significant risk. ■
Dr. Seidman is a medical oncologist at Memorial Sloan-Kettering Cancer Center, New York.
Disclosure: Dr. Seidman reported no potential conflicts of interest.
1. Darby SC, Ewertz M, McGale P, et al: Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368:987-998, 2013.
2. Patt DA, Goodwin JS, Yong-Fang K, et al: Cardiac morbidity of adjuvant radiotherapy for breast cancer. J Clin Oncol 23:7475-7482, 2005.
3. Giordano SH, Kuo YF, Freeman JL, et al: Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 97:419-424, 2005.
4. Chung E, Corbett JR, Moran JM, et al: Is there a dose-response relationship for heart disease with low-dose radiation therapy? Int J Rad Oncol Biol Phys 85:959-964, 2012.
5. Halyard MY, Pisansky TM, Dueck AC, et al: Radiotherapy and adjuvant trastuzumab in operable breast cancer: Tolerability and adverse event data from the NCCTG phase III trial N9831. J Clin Oncol 27:2638-2644, 2009.
A population-based case-control study reported by Sarah C. Darby, PhD, Professor of Medical Statistics in the Clinical Trial Service Unit and Epidemiologic Studies Unit at the University of Oxford, and colleagues in The New England Journal of Medicine indicates that incidental exposure of the heart ...
The paper by Darby et al provides extremely important information on quantitative estimates of the effect of radiotherapy on coronary events in women with breast cancer.1 The authors have determined a direct relationship between radiation dose and effects on the heart and provide strong evidence...