Cardio-Oncology Resource Center

Cardio-Oncology Resource Center

Disclosures: Carlson is an employee of Bristol Myers Squibb. Please see the study for all other authors’ relevant financial disclosures. Bates and the other editorial authors report no relevant financial disclosures.
September 21, 2021
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CAD risk may be elevated in women with left-sided radiation for breast cancer

Disclosures: Carlson is an employee of Bristol Myers Squibb. Please see the study for all other authors’ relevant financial disclosures. Bates and the other editorial authors report no relevant financial disclosures.
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The risk for CAD in women with stage I or II breast cancer who received left-sided radiation therapy may be more than twofold greater compared with those who received right-sided radiation.

According to a study published in JACC: CardioOncology, the 10-year survival rate of breast cancer among women who are diagnosed at younger than 50 years is 93.4% for stage I disease and 76.1% for stage II disease, and currently, 47% of women with stage I or II disease undergo radiation therapy.

Graphical depiction of data presented in article
Data were derived from Carlson LE, et al. JACC CardioOncol. 2021;doi:10.1016/j.jaccao.2021.07.008.

“Recent studies have suggested that irradiation of specific heart structures, along with the presence of cardiovascular risk factors, are important determinants of future radiation-induced cardiovascular disease,” Lauren E. Carlson, MPH, who was a research study assistant at Memorial Sloan Kettering Cancer Center at the time of the study and is now a manager of biostatistics at Bristol Myers Squibb, and colleagues wrote. “Additionally, radiation-associated cardiovascular disease has a latency of at least 5 years, requiring long-term follow-up of large numbers of breast cancer survivors to assess subsequent cardiovascular disease events.”

The WECARE follow-up study

To evaluate the late effects of radiation therapy on risk for CAD, researchers conducted the WECARE follow-up study, a population-based case-control analysis of women with contralateral and unilateral breast cancer who were diagnosed before age 55 years. A total of 972 women (median age at diagnosis, 46 years) completed the WECARE CV health questionnaire. Using these self-reported data, researchers evaluated the risk for radiation-associated CAD among women who underwent left-sided radiation therapy compared with those who received right-sided radiation. Median follow-up was 14 years.

According to the study, participants who underwent right- or left-sided radiation therapy experienced similar event-free survival for CAD up to 5 years follow-up; however, event-free survival among those who received left-sided radiation therapy decreased at each subsequent time interval after 5 years (P = .01).

The cumulative 27.5-year incidence of CAD among women who received left-sided radiation therapy was 10.5% compared with 5.8% for women who received right-sided radiation therapy (P = .01).

Among women who were diagnosed with breast cancer at age 25 to 39 years, the cumulative incidence of CAD was 5.9% for those who received left-sided radiation therapy and 0% for women who received right-sided radiation therapy. For women who were diagnosed at age 40 to 54 years, the 27.5-year incidence of CAD was 18.7% for those who received left-sided radiation therapy and 6.8% for women who received right-sided radiation therapy.

Researchers reported that the absolute rate of CAD among women who received left-sided radiation therapy was 4.7 events per 1,000 person-years compared with 2.1 events per 1,000 person-years among those who underwent right-sided radiation therapy.

Moreover, left-sided radiation therapy for treatment of breast cancer was associated with a more than twofold greater risk for CAD compared with right-sided radiation therapy (HR = 2.5; 95% CI, 1.3-4.7). Findings were similar when the analysis was restricted to women with stage I breast cancer (HR = 2.8; 95% CI, 1.3-6.1).

The researchers observed no significant association between baseline risk factors and risk for CAD after left-sided radiation therapy.

Additionally, risk for CAD was not modified by the presence of chemotherapy, hormone therapy for breast cancer or anthracycline exposure (P for heterogeneity for all > .05).

Underscoring the need for surveillance

In a related editorial, James E. Bates, MD, assistant professor in the department of radiation oncology at Emory University School of Medicine, and colleagues wrote: “Burgeoning evidence across disease sites suggests that the specific radiotherapy dose to substructures, specifically the left anterior descending artery and left ventricle may be more predictive of cardiac disease than radiotherapy dose to the whole heart. Better understanding these relationships is critical to developing actionable dose constraints that can be used in radiotherapy planning to minimize the long-term cardiac risk in these patients.

“Carlson et al reaffirm the enhanced risk for late cardiac disease conferred by radiotherapy to left-sided breast cancer in younger adult patients,” Bates and colleagues wrote. “This adds to our depth of knowledge in this area and underscores the need for continued surveillance in this population. Just as maximizing displacement of the heart outside of the radiotherapy field was developed as result of collaboration between cardiologists and radiation oncologists, integration of preplanning radiotherapy protocols with teams experienced in cardiac physiology, imaging, and radiation simulation will continue to benefit future breast cancer survivors.”

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