CAD in Young Women After Radiation Therapy for Breast Cancer

Quick Takes

  • This study is an analysis of the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) registry, which studied women by stage I or II invasive breast cancer diagnosed before 55 years of age.
  • Young women treated with radiation therapy (RT) for left-sided breast cancer had over twice the risk of CAD compared with women treated with RT for right-sided breast cancer.
  • The association was not modified by cardiovascular risk factors. The impact of radiation dose was not studied.

Study Questions:

What is the risk of radiation-associated coronary artery disease (CAD) in young women who survived breast cancer?

Methods:

The authors leveraged the population-based WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study and identified 972 women who were <55 years of age when diagnosed with stage I or II breast cancer between 1985 and 2008 and received radiation for breast cancer. Women with a prior history of heart disease were excluded. Participants had completed a cardiovascular health questionnaire and were contacted to identify cardiovascular events. The primary outcome was incident CAD, defined as first diagnosis of myocardial infarction, coronary heart disease, or angina pectoris requiring medication. The exposure of interest was left- versus right-sided treatment with radiation therapy (RT). A time to event analysis was performed.

Results:

The median age of breast cancer diagnosis was 46 years, with a median follow-up time of 14 years (range 1-29 years). Clinical characteristics were evenly distributed between groups (left vs. right RT). A total of 46 participants reported a CAD diagnosis, and 91% of CAD diagnoses occurred >5 years after treatment with RT. The 27.5-year cumulative incidences of CAD for women receiving left- versus right-sided RT were 10.5% and 5.8%, respectively, with an adjusted hazard ratio of 2.5 (95% confidence interval, 1.3-4.7) for left compared to right RT. The association did not differ according to age, hypertension, hypercholesterolemia, or anthracycline exposure.

Conclusions:

Young women treated with RT for left-sided breast cancer had over twice the risk of CAD compared with women treated with RT for right-sided breast cancer.

Perspective:

This study is a strong addition to the literature on the risks of RT-associated CAD through its focus on younger women and the prospective assessment. Both groups of patients (right RT vs. left RT) were well-balanced with regard to risk factors and use of breast cancer therapies. The authors also performed extensive sensitivity analyses. Its limitations, however, include the relatively smaller sample size, the inability to account for radiation dose, and the reliance on self-reported CAD events rather than adjudicated events. The lack of effect modification by traditional risk factors (including smoking) is, however, odd and is either due to the smaller sample size or the possibility that RT-induced CAD occurs in a pathway independent of that of these risk factors. Nevertheless, this study, in conjunction with recent observational findings suggesting statins could reduce the risk of RT-related CAD, warrant the conduct of a trial examining risk reduction strategies such as statins in this patient population.

Clinical Topics: Cardio-Oncology, Cardiovascular Care Team, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Nonstatins, Novel Agents, Statins

Keywords: Angina Pectoris, Breast Neoplasms, Cardiotoxicity, Coronary Artery Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Middle Aged, Myocardial Infarction, Myocardial Ischemia, Primary Prevention, Radiation, Radiation Dosage, Risk Factors, Unilateral Breast Neoplasms, Women


< Back to Listings