Long-Term Risk of Cardiovascular Disease in 10-Year Survivors of Breast Cancer

TLDR

Radiotherapy for breast cancer in the 1970s has been linked to higher cardiovascular disease risk, yet evidence for modern regimens remains unclear, and little is known about long‑term risk by specific radiation fields or interactions with traditional risk factors. The study aimed to determine treatment‑specific cardiovascular disease incidence in 4 414 breast‑cancer survivors followed for at least 10 years, treated between 1970 and 1986. Cardiovascular risk was compared to general population rates and assessed with Cox proportional‑hazards models over a median 18‑year follow‑up. Survivors experienced a 30 % excess cardiovascular risk (SIR 1.30), with no increase from breast irradiation alone but markedly higher risk from internal mammary chain irradiation—especially before 1980—while heart failure and valvular disease remained elevated after 1980; combined radiotherapy and chemotherapy further raised heart‑failure risk, and smoking amplified myocardial‑infarction risk, highlighting the importance of smoking cessation counseling.

Abstract

Radiotherapy for breast cancer as delivered in the 1970s has been associated with increased risk of cardiovascular disease, but recent studies of associations with modern regimens have been inconclusive. Few data on long-term cardiovascular disease risk according to specific radiation fields are available, and interaction with known cardiovascular risk factors has not been examined.We studied treatment-specific incidence of cardiovascular disease in 4414 10-year survivors of breast cancer who were treated from 1970 through 1986. Risk of cardiovascular disease in these patients was compared with general population rates and evaluated in Cox proportional hazards regression models. All statistical tests were two-sided.After a median follow-up of 18 years, 942 cardiovascular events were observed (standardized incidence ratio = 1.30, 95% confidence interval [CI] = 1.22 to 1.38; corresponding to 62.9 excess cases per 10,000 patient-years). Breast irradiation only was not associated with increased risk of cardiovascular disease. However, radiotherapy to either the left or right side of the internal mammary chain was associated with increased cardiovascular disease risk for the treatment period 1970-1979 (for myocardial infarction, hazard ratio [HR] = 2.55, 95% CI = 1.55 to 4.19; P<.001; for congestive heart failure, HR = 1.72, 95% CI = 1.22 to 2.41; P = .002) compared with no radiotherapy. Among patients who received internal mammary chain radiotherapy after 1979, risk of myocardial infarction declined over time toward unity, whereas the risks of congestive heart failure (HR = 2.66, 95% CI = 1.27 to 5.61; P = .01) and valvular dysfunction (HR = 3.17, 95% CI = 1.90 to 5.29; P<.001) remained increased. Patients who underwent radiotherapy plus adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) after 1979 had a higher risk of congestive heart failure than patients who were treated with radiotherapy only (HR = 1.85, 95% CI = 1.25 to 2.73; P = .002). Smoking and radiotherapy together were associated with a more than additive effect on risk of myocardial infarction (HR = 3.04, 95% CI = 2.03 to 4.55; P for departure from additivity = .039).Radiotherapy as administered from the 1980s onward is associated with an increased risk of cardiovascular disease. Irradiated breast cancer patients should be advised to refrain from smoking to reduce their risk for cardiovascular disease.