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. 2021 Sep 21;3(3):381-392.
doi: 10.1016/j.jaccao.2021.07.008. eCollection 2021 Sep.

Coronary Artery Disease in Young Women After Radiation Therapy for Breast Cancer: The WECARE Study

Lauren E Carlson  1 , Gordon P Watt  1 , Emily S Tonorezos  2 , Eric J Chow  3 , Anthony F Yu  1 , Meghan Woods  1 , Charles F Lynch  4 , Esther M John  5 , Lene Mellemkjӕr  6 , Jennifer D Brooks  7 , Julia A Knight  7   8 , Anne S Reiner  1 , Xiaolin Liang  1 , Susan A Smith  9 , Leslie Bernstein  10 , Lawrence T Dauer  1 , Laura I Cerviño  1 , Rebecca M Howell  8 , Roy E Shore  11 , John D Boice Jr  12   13 , Jonine L Bernstein  1 ; WECARE Study Collaborative Group
Collaborators, Affiliations

Coronary Artery Disease in Young Women After Radiation Therapy for Breast Cancer: The WECARE Study

Lauren E Carlson et al. JACC CardioOncol. .

Abstract

Background: Radiation therapy (RT) for breast cancer increases risk of coronary artery disease (CAD). Women treated for left- vs right-sided breast cancer receive greater heart radiation exposure, which may further increase this risk. The risk of radiation-associated CAD specifically among younger breast cancer survivors is not well defined.

Objectives: The purpose of this study was to report CAD risk among participants in the Women's Environmental Cancer and Radiation Epidemiology Study.

Methods: A total of 1,583 women who were <55 years of age when diagnosed with breast cancer between 1985 and 2008 completed a cardiovascular health questionnaire. Risk of radiation-associated CAD was evaluated by comparing women treated with left-sided RT with women treated with right-sided RT using multivariable Cox proportional hazards models. Effect modification by treatment and cardiovascular risk factors was examined.

Results: In total, 517 women who did not receive RT and 94 women who had a pre-existing cardiovascular disease diagnosis were excluded, leaving 972 women eligible for analysis. Their median follow-up time was 14 years (range 1-29 years). The 27.5-year cumulative incidences of CAD for women receiving left- vs right-sided RT were 10.5% and 5.8%, respectively (P = 0.010). The corresponding HR of CAD for left- vs right-sided RT in the multivariable Cox model was 2.5 (95% CI: 1.3-4.7). There was no statistically significant effect modification by any factor evaluated.

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. Laterality of RT is independently associated with an increased risk of CAD and should be considered in survivorship care of younger breast cancer patients.

Keywords: BMI, body mass index; CAD, coronary artery disease; RT, radiation therapy; epidemiology; ischemic disease; prevention; risk factor; treatment; women’s oncology.

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Conflict of interest statement

This work was supported by U01 CA083178, “Breast Cancer Radiation Exposure and the ATM Gene”; R01 CA097397, “Interaction of Radiation, BRCA 1/2, and Breast Cancer”; R01 CA114236, “Breast Cancer, Radiation and the ATM-Chek2 Pathway”; R01CA129639, “Genome-Wide Association Study of Radiation Exposure and Bilateral Breast Cancer”; CA008748, “Cancer Center Support Grant”; CA168339, “Mammographic Density and Risk of Contralateral Breast Cancer”; and CA206464, “Molecular pathoepidemiology of contralateral breast cancer.” Ms Carlson is employed by Bristol Myers Squibb, unrelated to this study. Dr Chow has received research funding from Abbott, unrelated to this study. Dr Yu has received consulting fees from Genentech and Ichnos Sciences. Dr Mellemkjӕr has an immediate family member employed at Novo Nordisk, and has an immediate family member who owns stocks in Novo Nordisk, unrelated to this study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Selection of Participants Participants were selected from the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) Study phases I and II. Participants must have been living at the time of the follow-up survey.
Figure 2
Figure 2
Event-Free Survival Probability of Coronary Artery Disease Young women under age 55 years receiving left-sided radiation therapy (RT) for breast cancer had a statistically significantly shorter follow-up time than women receiving right-sided RT for breast cancer (P = 0.01).
Central Illustration
Central Illustration
CAD After RT for Breast Cancer: The WECARE Study Women <55 years of age at breast cancer diagnosis who were participants in the WECARE (Women’s Environmental and Radiation Epidemiology) Study were surveyed for coronary artery disease (CAD) outcomes following radiation therapy (RT). Participants were followed from the time of their breast cancer diagnosis until a CAD diagnosis or censoring event. Women who received left-sided RT were at more than twice the risk of a CAD event than women who received right-sided RT.
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