Associations between hematopoietic growth factors and risks of venous thromboembolism, stroke, ischemic heart disease and myelodysplastic syndrome: findings from a large population-based cohort of women with breast cancer

Purpose: To determine the risk of venous thromboembolism (VTE), stroke, ischemic heart disease, and myelodysplastic syndrome (MDS) in association with the receipt of colony-stimulating factors (CSFs) and/or erythropoiesis-stimulating agents (ESAs) in women with breast cancer. Methods: We studied 77,233 women with breast cancer aged ≥65 in 1992–2009 from the Surveillance, Epidemiology, and End Results-Medicare linked data with up to 19 years of follow-up. Results: Incidence of VTE increased from 9 cases in women receiving no chemotherapy and no CSFs/ESAs to 22.79 cases per 1,000 person-years in those receiving chemotherapy with CSFs and ESAs. Women with chemotherapy who received both CSFs and ESAs (adjusted hazard ratio and 95 % confidence interval 2.01, 1.80–2.25) or received ESAs without CSFs (2.03, 1.74–2.36) were twice as likely to develop VTE than those receiving no chemotherapy and no CSFs/ESAs, whereas those receiving CSF alone without ESA were 64 % more likely to have VTE (1.64, 1.45–1.85). Risk of MDS was significantly increased by fivefold in patients receiving ESA following chemotherapy. Conclusions: Receipts of CSFs and ESAs were significantly associated with an increased risk of VTE in women with breast cancer. Use of ESAs was significantly associated with substantially increased risks of MDS. These findings support those of previous studies.