Time-dependent risk and predictors of venous thromboembolism in breast cancer patients: A population-based cohort study

Cancer. 2017 Feb 1;123(3):468-475. doi: 10.1002/cncr.30364. Epub 2016 Oct 11.

Abstract

Background: Venous thromboembolism (VTE) is a serious complication of cancer and its treatment. The current study assessed the risk and clinical predictors of VTE in breast cancer patients by time since diagnosis.

Methods: This Swedish population-based study included 8338 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region with complete follow-up until 2012. Their incidence of VTE was compared with the incidence among 39,013 age-matched reference individuals from the general population. Cox and flexible parametric models were used to examine associations with patient, tumor, and treatment characteristics, accounting for time-dependent effects.

Results: Over a median follow-up of 7.2 years, 426 breast cancer patients experienced a VTE event (cumulative incidence, 5.1%). The VTE incidence was 3-fold increased (hazard ratio [HR], 3.28; 95% confidence interval [CI], 2.87-3.74) in comparison with the incidence in the general population and was highest 6 months after diagnosis (HR, 8.62; 95% CI, 6.56-11.33) with a sustained increase in risk thereafter (HR at 5 years, 2.19; 95% CI, 1.80-2.67). Independent predictors of VTE included the following: older age, being overweight, preexisting VTE, comorbid disease, tumor size > 40 mm, progesterone receptor (PR)-negative status, more than 4 affected lymph nodes, and receipt of chemo- and endocrine therapy. The impact of chemotherapy was limited to early-onset VTE, whereas comorbid disease and PR-negative status were more strongly associated with late-onset events.

Conclusions: This study confirms the long-term risk of VTE in breast cancer patients and identifies a comprehensive set of clinical risk predictors. Temporal associations with patient, tumor, and treatment characteristics provide insight into the time-dependent etiology of VTE. Cancer 2017;123:468-475. © 2016 American Cancer Society.

Keywords: breast cancer; epidemiology; predictors; time-dependent risk modeling; venous thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Breast Neoplasms / complications*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Female
  • Humans
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Sweden
  • Time Factors
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / pathology*