Left-Breast Radiation Tied to Doubling of CAD Risk in Young Women

Patrice Wendling

September 23, 2021

Long-term results suggest left-sided radiotherapy (RT) is an independent risk factor for future coronary artery disease (CAD) in young breast cancer survivors, underscoring the need for continued surveillance in these individuals.

After a median follow-up of 14 years in more than 900 women diagnosed with breast cancer before age 55, the 27.5-year cumulative incidence of CAD was 10.5% in those receiving left-sided RT and 5.8% in those receiving right-sided RT (P = .10).

In the youngest patients, those 25 to 39 years, the 27.5-year CAD risks with left- vs right-sided RT were 5.9% and 0%, respectively.

After multivariate adjustment, women treated with left-sided RT had more than twice the risk for CAD than those treated with right-sided RT (hazard ratio [HR], 2.5; 95% CI, 1.3 - 4.7), according to results published in JACC: CardioOncology.

"The main differences in this paper are, first, that it was generally a younger population than has been studied before and, second, that we had relatively long follow-up with complete data on important variables, such as history of hypercholesterolemia and other factors, that may increase the risk of future chronic coronary artery disease," Gordon P. Watt, PhD, Memorial Sloan Kettering Cancer Institute, New York City, told Medscape Medical News.

RT is known to increase the risk for CAD in breast cancer survivors, with a seminal study in an older cohort demonstrating a 7.4% increased risk for major coronary events for each 1 Gy increase in the mean radiation dose delivered to the heart.

The current study was based on 972 participants in the population-based WECARE study who had no history of cardiovascular disease before a stage 1 or 2 invasive breast cancer diagnosis (median age, 46 years) between 1985 and 2008 and completed standardized follow-up cardiovascular health questionnaires.

The mean radiation dose was 55 Gy (range, 45 - 65 Gy), 60% of patients received chemotherapy, and 30% were treated with anthracyclines.

During follow-up (range, 1 - 29 years), 46 patients reported a CAD diagnosis, and 91% of these diagnoses occurred more than 5 years after radiation therapy.

"It's generally accepted that radiation-associated outcomes, such as radiation-associated heart disease, generally has a latency of at least 5 years," Watt said. "So that's why long-term follow-up for cardiac disease in women receiving radiation is so important."

The absolute rate of CAD among women treated with left-sided RT was 4.7 events per 1000 person-years, compared with 2.1 events per 1000 person-years among those treated with right-sided RT.

"My takeaway from this is, yes, there is clearly a signal of higher probability of coronary artery disease risk amongst women who received radiation therapy, in particular left-sided radiation, but there are a couple of things that need to be taken into effect," Suma H. Konety, MD, director of the cardio-oncology program at the University of Minnesota, Minneapolis, told Medscape Medical News.

She noted that the absolute number of women with CAD is still small and that this is self-reported coronary disease in a population that's dealing with a cancer diagnosis and prognosis but has also been told they're at risk for cardiomyopathy from chemotherapy. "So, there's an extremely heightened concern amongst these patients and oftentimes they develop chest pain and such when they come in, and you never know without reviewing the medical records what this coronary disease was exactly."

More important, radiation techniques like prone positioning, having the patient hold their breath, and proton-beam therapy have evolved to mitigate the risk for radiation injury to the heart, observed Konety. "So, we're not actually evaluating the modern-day radiation techniques on the risk of heart disease."

Nonetheless, the findings should give clinicians pause. "I think what this should translate to, hopefully, is when we as physicians see patients and follow-up that we take left-side radiation as one of the risk factors for heart disease," she said. "This needs to be accounted for in people when we do the survivorship care."

The authors acknowledge that detailed cardiac dosimetry was not available and that women treated with contemporary RT techniques "will likely have a lower risk of CAD compared with that seen in our study."

An accompanying editorial points out that burgeoning evidence suggests that the specific RT dose to substructures, specifically the left anterior descending artery and left ventricle, may be more predictive of cardiac disease that RT dose to the whole heart.

"Better understanding these relationships is critical to developing actionable dose constraints that can be used in RT planning to minimize the long-term cardiac risk in these patients," say James E. Bates, MD, Winship Cancer Institute, Emory University, Atlanta, and colleagues.

The editorialists also highlight the need for patient education, as well as prompt and aggressive attention to reversible or modifiable cardiac risk factors, such as hyperlipidemia and hypertension, that affect the cardiovascular late effects of RT.

"Involvement of a cardio-oncologist may increase the likelihood of consistent management of cardiac risk factors and serve as a resource for young women who have survived breast cancer in minimizing the long-term risk of CVD from RT," Bates and colleagues suggest.

The work was supported by National Institutes of Health grants. Watt and the editorialists report no relevant financial relationships.

JACC CardioOncol. 2021;3:381-392, 393-396. Full text, Editorial

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