Cardiovascular Disease in Survivors of Breast Cancer: A Case-Cohort Study

Hatem Hamood Community Practice, Leumit Health Services, Karmiel, Northern Region, Israel School of Public Health, University of Haifa, Haifa, Israel Rola Hamood, MPH School of Public Health, University of Haifa, Haifa, Israel Ilya Merhasin, MA Community Practice, Leumit Health Services, Karmiel, Northern Region, Israel Lital Keinan-Boker Lital Keinan-Boker, MD, PhD, MPH School of Public Health, University of Haifa, Haifa, Israel Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel

Background: Adjuvant therapy for breast cancer improves overall survival, but its long-term adverse effect on cardiovascular health of survivors is still controversial.

Purpose: To examine the association between chemotherapy and/or radiotherapy and subsequent risk of cardiovascular disease (CVD) in breast cancer survivors.

Patients and Methods: We conducted a patient-based case-cohort study of 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 (HR) 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%). Lifestyle components, collected post-CVD incidence, indicated higher prevalence of obesity, 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, 2.75; 95%CI, 1.23-6.16; P=.014), outpatient visits (HR per average 10-annual visits, 1.74; 95%CI, 1.44-2.10; P<.001), employment transition between breast cancer diagnosis and treatment: job loss versus no change (HR, 23.68; 95%CI, 10.96-51.12; P<.001), and inversely associated with education (HR per one-year increment, 0.87; 95%CI, 0.79-0.96; P=.005). Breast laterality and chemotherapy did not confer increased risk of CVD.

Conclusion: Radiotherapy administered as an adjuvant treatment for breast cancer elevates risk of CVD. Withholding radiation treatment is not justified given the long-term benefit it imparts on overall survival. Preventive strategies should be directed to surveillance for radiotherapy-related CVD dysfunction. Efforts should also be directed into lifestyle modifications and occupational rehabilitation in high-risk patients of CVD.

Keywords: Breast cancer, cardiovascular disease, radiotherapy, chemotherapy, risk factors, survivorship

Hatem Hamood
Hatem Hamood








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