title: Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen - results from a prospective, single center, case control study.
abstract: BACKGROUND
  Estimates of the risk ratio of tamoxifen-associated venous thromboembolism (VTE) in breast cancer patients range from 2.4 to 7.1. The occurrence of thrombosis in patients with breast cancer complicates the clinical condition and causes a change of treatment. Our study was conducted in order to investigate the influence of patient-related risk factors for thrombosis development in breast cancer patients whose treatment included adjuvant tamoxifen.
  
  
  METHODS
  The prospective, single center, case control study included 150 breast cancer women, 50 whom developed venous thrombosis during adjuvant tamoxifen and 100 whom did not have thrombosis, as a control group. Patient-related risk factors such as: age, body mass index, previous VTE, varicose veins, concomitant diseases, the presence of prothrombotic mutations (FV Leiden, FII G20210A) and FVIII activity were evaluated in both groups.
  
  
  RESULTS
  In respect of prothrombotic mutations, the FV Leiden mutation was present in a higher number of women from the VTE group (10/50 vs 7/100; P=0.020). Additionally, FVIII activity was significantly higher in the VTE group; median (IQR), of 1.79 (0.69) vs 1.45 (0.55); P<0.001 and more women in this group (24/50 vs 34/100) had increased FVIII activity; P=0.020. In those women with FVIII>1.5IU/ml, who were carriers of prothrombotic mutations, an OR of 3.76 (CI 95% 1.276-11.096; P=0.016) was obtained for VTE.
  
  
  CONCLUSIONS
  The results of our study showed that the factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen.
authors.affiliation: Faculty of Medicine, University of Belgrade, Serbia; Blood Transfusion Institute of Serbia, Hemostasis Department, Belgrade, Serbia. Electronic address: mkovac008@gmail.com.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kovac
authors.affiliation: National Cancer Research Institute, Serbia. Electronic address: zeljko.kovac.2010@gmail.com.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Kovac
authors.affiliation: National Cancer Research Institute, Serbia. Electronic address: zoricant@ncrs.ac.rs.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Tomasevic
authors.affiliation: National Cancer Research Institute, Serbia. Electronic address: slafimi@gmail.com.
authors.forename: Slavko
authors.initials: S
authors.lastname: Vucicevic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. Electronic address: pq20210a@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Djordjevic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. Electronic address: iva.pruner@gmail.com.
authors.forename: Iva
authors.initials: I
authors.lastname: Pruner
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. Electronic address: dragica.radojkovic@gmail.com.
authors.forename: Dragica
authors.initials: D
authors.lastname: Radojkovic
mesh_terms: D020016:Activated Protein C Resistance / Q000235:genetics*; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy; D018275:Carcinoma, Lobular / Q000188:drug therapy; D002291:Carcinoma, Papillary / Q000188:drug therapy; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D005165:Factor V / Q000235:genetics*; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D013629:Tamoxifen / Q000009:adverse effects*; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000235:genetics
chemical_list: D018931:Antineoplastic Agents, Hormonal; C095381:factor V Leiden; D013629:Tamoxifen; D005165:Factor V; D005169:Factor VIII
keywords: Breast cancer; FV Leiden; Factor VIII; Tamoxifen; Venous thromboembolism