When are breast cancer patients at highest risk of venous thromboembolism? A cohort study using English health care data

Patients with breast cancer are at increased risk of venous thromboembolism (VTE), particularly in the peridiagnosis period. However, no previous epidemiologic studies have investigated the relative impact of breast cancer treatments in a time-dependent manner. We aimed to determine the impact of breast cancer stage, biology, and treatment on the absolute and relative risks of VTE by using several recently linked data sources from England. Our cohort comprised 13,202 patients with breast cancer from the Clinical Practice Research Datalink (linked to Hospital Episode Statistics and Cancer Registry data) diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, treatment-related, and biological factors independently affected VTE risk. Women had an annual VTE incidence of 6% while receiving chemotherapy which was 10.8-fold higher (95% confidence interval CI, 8.2-14.4; absolute rate AR, 59.6 per 1000 person-years) than that in women who did not receive chemotherapy. After surgery, the risk was significantly increased in the first month (hazard ratio HR, 2.2; 95% CI, 1.4-3.4; AR, 23.5; reference group, no surgery), but the risk was not increased after the first month. Risk of VTE was noticeably higher in the 3 months after initiation of tamoxifen compared with the risk before therapy (HR, 5.5; 95% CI, 2.3-12.7; AR, 24.1); however, initiating therapy with aromatase inhibitors was not associated with VTE (HR, 0.8; 95% CI, 0.5-1.4; AR, 28.3). In conclusion, women receiving chemotherapy for breast cancer have a clinically important risk of VTE, whereas an increased risk of VTE immediately after endocrine therapy is restricted to tamoxifen.