Time-Dependent Association Between Breast Cancer and Risk of Ischemic Stroke

BACKGROUND AND OBJECTIVES: The association between breast cancer diagnosis and treatment and the risk of incident ischemic stroke remains unclear. We investigated ischemic stroke risk among breast cancer survivors and evaluated associations by age, follow-up duration, and type of cancer treatment. METHODS: We conducted a nationwide, retrospective, matched cohort study using the Korean National Health Insurance Service database. Women aged 18 years and older with newly diagnosed breast cancer who underwent breast cancer surgery between January 2010 and December 2016 and had no prior stroke were identified. Each was matched 1:3 by birth year to cancer-free women. The primary outcome was first ischemic stroke, defined as hospitalization with International Classification of Disease, Tenth Revision codes I63/I64 plus inpatient brain CT or MRI. Subdistribution hazard ratios (sHRs) and 95% CIs were estimated using Fine-Gray models that accounted for death as a competing risk and adjusted for sociodemographic factors and cardiovascular and non-CV comorbidities. RESULTS: We analyzed 107,606 breast cancer surgery survivors (mean age, 50.0 years) and 322,818 matched cancer-free women. Over a mean 7.2-year follow-up, ischemic stroke occurred in 1,155 survivors (1.07%). Stroke risk was elevated shortly after breast cancer diagnosis (1-year sHR 1.59; 95% CI 1.34-1.89; 3-year sHR 1.17; 95% CI 1.05-1.30) compared with cancer-free women, with stronger associations at 3 and 6 months after diagnosis across all age groups. Over the long term, survivors had a slightly lower risk of stroke (sHR 0.94; 95% CI 0.88-1.00), and in a 1-year landmark analysis including only event-free individuals, the risk was lower (sHR 0.87, 95% CI 0.81-0.93). Among survivors, anthracycline use (sHR 1.25) and combined tamoxifen-aromatase inhibitor therapy (sHR 1.49) were associated with increased risk of stroke, whereas radiation therapy was associated with decreased risk (sHR 0.84). These associations attenuated and became nonsignificant beyond 1 year. Stroke risk was also higher among survivors with low income, hypertension, diabetes, or current smoking. DISCUSSION: The association between breast cancer and ischemic stroke risk is time dependent, with a short-term increase after diagnosis and treatment followed by a gradual decline over time. These findings highlight the need for proactive stroke risk management, including early CV assessment and ongoing monitoring for thromboembolic events during survivorship.