Contact: Amanda Jekowsky, ajekowsk@acc.org, 202-375-6645

In one of the few studies with long-term data of over 20 years, researchers found that women who received radiotherapy before 1984 as part of their breast cancer treatment had significantly higher rates of death from cardiovascular disease than those who did not receive radiation. The findings, published in the January 25, 2011, issue of the Journal of the American College of CArdiol shed light on some of breast cancer’s treatment –related toxicities, which have been a greater concern as the disease becomes increasingly survivable, resulting in a growing population of long-term survivors.

For the study, a French and Swedish research team tracked 4,456 women who had received treatment for breast cancer between 1954 and 1984 at the Institut Gustave Roussy in Villejuif, France. To be included in the analysis, the women had to be at least a 5-year survivor; they were followed for an average of 28 years.

Using medical records and national registries, the researchers tracked the treatment provided to each study participant and the mortality information. They found that more than two-thirds of the patients received radiotherapy. They also found that 2,637 women in the cohort died before the age of 95 years (the study’s cut-off age). The cause of death could be ascertained for 92.6% (2,441) of the deaths. Of these, 421 deaths were attributed to cardiovascular diseases, with 236 caused by cardiac diseases and 185 ascribed to vascular diseases.

After conducting multivariate analysis and adjusting for participant age, the researchers found that cardiac mortality was 1.76-fold (95% confidence interval [CI]: 1.34 to 2.31) higher among women who received radiotherapy than among those who had not. Similarly, mortality caused by cardiovascular diseases was 1.56-fold (95% CI: 1.27 to 1.90) higher among women who received radiation. Death from only vascular diseases was not significantly different between the two groups.

The data also showed a difference in risk based on tumor site. After controlling for certain variables, the team found that women who had radiotherapy for a left-sided breast cancer had a 1.28-fold (95% CI: 0.92 to 1.78) higher risk of cardiac disease than those who received radiotherapy for a right-sided tumor. This risk increased with the increasing length of follow-up.

The research team concluded that the results “confirm that radiotherapy for breast cancer, such as that practiced until the mid-1980s, increased the long-term risk of death from cardiac disease.” While study author Florent de Vathaire, Ph.D., from the Radiation Epidemiology Group at INSERM and the Institut Gustave Roussy acknowledges that radiotherapy techniques “have greatly advanced since 1984,” he adds that the growing use of anthracyclines in recent years has added to the cardiac risk, necessitating that women treated with modern radiotherapy techniques still “need to be followed for cardiovascular monitoring.”

In an accompanying editorial, Ronald M. Witteles, M.D., from the Division of Cardiovascular Medicine at Stanford University School of Medicine, calls the current study “an important contribution to the literature,” as it provides “convincing evidence” about radiotherapy’s long-term cardiovascular effects. Dr. Witteles adds that the study’s findings on left-sided tumors are especially compelling, and also notes that the growing use of anthracyclines and anti-HER2 therapy across the past two decades likely further increases the cardiac risk. As he warns that radiation doses “remain substantial” despite significant advances in radiation technology, Dr. Witteles suggests that physicians should carefully approach the issue of radiotherapy “with eyes wide open.”

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