title: Time-dependent risk and predictors of venous thromboembolism in breast cancer patients: A population-based cohort study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Brand
authors.affiliation: Department of Oncology-Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Elham
authors.initials: E
authors.lastname: Hedayati
authors.affiliation: Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nirmala
authors.identifier: 0000-0003-0568-8863
authors.initials: N
authors.lastname: Bhoo-Pathy
authors.affiliation: Department of Oncology-Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Ludvigsson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D013548:Sweden; D013997:Time Factors; D054556:Venous Thromboembolism / Q000209:etiology / Q000473:pathology*
keywords: breast cancer; epidemiology; predictors; time-dependent risk modeling; venous thromboembolism