Abstract / Summary
Abstract Purpose Targeted therapies for breast cancer, including CDK4/6, PARP, mTOR, and PI3K inhibitors, have raised concerns regarding thrombosis risk, but real-world data comparing these agents remain limited. We investigated thrombosis incidence and risk factors in a large national cohort of breast cancer patients. Methods In this retrospective cohort study using the TriNetX national database, we evaluated the thrombotic risk and associated factors among patients with breast cancer treated with these therapies. The primary outcome was any arterial or venous thrombotic event. Results Among 4,165 patients on targeted therapy, treatment with CDK4/6i was associated with increased risk of any thrombosis (HR 3.36, 95% CI 2.89–3.92) and venous thrombosis (HR 4.45, 95% CI 3.68–5.39). PARPi (HR 3.78, 95% CI 1.82–7.85; venous HR 5.79, 95% CI 2.52–13.3) and everolimus (HR 6.59, 95% CI 3.82–11.4; venous HR 9.67, 95% CI 5.29–17.7) showed similar associations. Within CDK4/6i, palbociclib carried the highest hazard for any thrombosis (HR 3.64, 95% CI 3.02–4.39) and venous thrombosis (HR 5.11, 95% CI 4.05–6.45). Nicotine dependence (HR 2.01, 95% CI 1.91–2.12), brain metastases (HR 4.20, 95% CI 2.98–5.93), and higher BMI (HR 1.03, 95% CI 1.03–1.03) were independent risk factors. Conclusion This real-world analysis demonstrates that CDK4/6i and everolimus were associated with increased risk of both arterial and venous thrombosis, while PARPi was specifically associated with venous thrombosis. Similar risk was seen across CDK4/6 inhibitor agents. These results support risk stratification tools incorporating both agent and patient-level factors to better inform clinical management.