Breast Cancer Radiation Therapy and the Risk of Acute Coronary Events: Insights From a Process-Oriented Model

• DOI: 10.1016/j.ijrobp.2022.06.082
• Publication Date: 2022-07-02T01:13:15Z
• Authors: Cristoforo Simonetto; Jan C. Kaiser; Veerle A.B. van d...; Johannes A. Lange...; Anne P.G. Crijns
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Risk Factors; Taurine; Humans; Breast Neoplasms; Female; Breast; Coronary Artery Disease; Atherosclerosis; 3. Good health

Acute coronary events (ACEs) are considered the most important side effect of radiation therapy (RT) for breast cancer, but underlying mechanisms still have to be identified. Process-oriented models mathematically describe the development of disease and provide a link between mechanisms and subsequent risk. Here, this link is exploited to learn about the underlying mechanisms from the observed age-time patterns of ACE risk.A process-oriented model of atherosclerosis and subsequent ACEs was applied to a contemporary breast cancer cohort of 810 patients with measurements of coronary artery calcification. Patients with prior ischemic heart disease were excluded. The process-oriented model describes disease development as a series of different stages. Different variants of the model were fitted to the data. In each variant, one stage was assumed to be accelerated in relation to mean heart dose.During a mean follow-up of 9.1 years, 25 ACEs occurred. The model reproduced the prevalence and associated risk of coronary calcifications. Mean heart dose significantly improved the fit only when implemented as affecting a late stage of atherosclerosis on already-existing complicated lesions (achieving P = .007). This can be understood by atherosclerosis being a slowly progressing disease. Therefore, an increase in ACEs a few years after RT requires advanced atherosclerosis at the time of RT.Risk of ACE increases within a few years in patients with advanced atherosclerosis at RT. Therefore, patients should be assessed for cardiovascular risk, and older patients need to be considered for heart-sparing techniques.