Risk of cardiovascular disease after radiotherapy in survivors of breast cancer: A case-cohort study

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Background: The current investigation examined the association between chemotherapy and/or radiotherapy and subsequent risk of cardiovascular disease (CVD) in breast cancer survivors. Methods: A case-cohort study was conducted, based on 2165 female breast cancer survivors recruited from “Leumit” healthcare fund, who were diagnosed with primary nonmetastatic invasive breast cancer between 2002 and 2012. A 20% random subcohort was sampled at baseline, and all CVD cases were identified. Adjusted hazard ratios (HRs) with 95% confidence intervals (CI) were estimated by weighted Cox proportional hazards models. Results: Of 2165 breast cancer survivors, 466 developed CVD over a mean follow-up of 5.7 years. The crude cumulative incidence of CVD accounting for death as a competing risk was 33.6% (95% CI, 29.6–37.6%) at 13 years of follow-up. Lifestyle components, collected post-CVD incidence, indicated a higher prevalence of poor nutrition and physical inactivity in CVD patients. In multivariable analyses, CVD was positively associated with radiotherapy without chemotherapy compared to no radiotherapy or chemotherapy (HR, 2.94; 95% CI, 1.17–7.38; p =.022), outpatient visits (HR per average 10-annual visits, 1.86; 95% CI, 1.50–2.31; p <.001), employment transition between breast cancer diagnosis and treatment: job loss versus no change (HR, 29.62; 95% CI, 12.72–68.97; p <.001), and inversely associated with education (HR per 1-year increment, 0.84; 95% CI, 0.75–0.94; p =.003). Conclusions: Radiotherapy administered as an adjuvant treatment for breast cancer elevates the risk of CVD. Preventive strategies should be directed to surveillance for radiotherapy-related CVD dysfunction. Efforts should also address lifestyle modifications and occupational rehabilitation in patients at a high risk of CVD.

Original languageEnglish
Pages (from-to)280-291
Number of pages12
JournalJournal of Cardiology
Issue number4
StatePublished - Apr 2019

Bibliographical note

Publisher Copyright:
© 2018 Japanese College of Cardiology


  • Breast cancer
  • Cardiovascular disease
  • Chemotherapy
  • Radiotherapy
  • Risk factors
  • Survivorship

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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