title: Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer.
abstract: BACKGROUND
  Tamoxifen use has been associated with increased risk of thromboembolic events (TEs) in women with breast cancer and women at high risk for the disease. Factor V Leiden (FVL) is the most common inherited clotting factor mutation and also confers increased thrombosis risk. We investigated whether FVL was associated with TE risk in women with early-stage breast cancer who took adjuvant tamoxifen.
  
  
  METHODS
  A case-control study was conducted among 34 Cancer and Leukemia Group B (CALGB) institutions. We matched each of 124 women who had experienced a documented TE while taking adjuvant tamoxifen for breast cancer (but who were not necessarily on a CALGB treatment trial) to two control subjects (women who took adjuvant tamoxifen but did not experience TE) by age at diagnosis (+/-5 years). DNA from blood was analyzed for FVL mutations. Conditional logistic regression was used to estimate odds ratios (ORs) and to evaluate other potential factors associated with TE and tamoxifen use. All P values are based on two-sided tests.
  
  
  RESULTS
  FVL mutations were identified in 23 (18.5%) case and 12 (4.8%) control subjects (OR = 4.66, 95% confidence interval = 2.14 to 10.14, P < .001). In the multivariable model, FVL mutation was associated with TE (OR = 4.73, 95% confidence interval = 2.10 to 10.68, P < .001). Other statistically significant factors associated with TE risk were personal history of TE and smoking.
  
  
  CONCLUSIONS
  Among women taking adjuvant tamoxifen for early-stage breast cancer, those who had a TE were nearly five times more likely to carry a FVL mutation than those who did not have a TE. Postmenopausal women should be evaluated for the FVL mutation before prescription of adjuvant tamoxifen if a positive test would alter therapeutic decision making.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. judy_garber@dfci.harvard.edu
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tolaney
authors.forename: Ellen
authors.initials: E
authors.lastname: Kaplan
authors.forename: Laura
authors.initials: L
authors.lastname: Archer
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Stephen
authors.initials: S
authors.lastname: Edge
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
authors.forename: Lynn
authors.initials: L
authors.lastname: Dressler
authors.forename: Electra D
authors.initials: ED
authors.lastname: Paskett
authors.forename: Electra M
authors.initials: EM
authors.lastname: Paskett
authors.forename: Gretchen
authors.initials: G
authors.lastname: Kimmick
authors.forename: James
authors.initials: J
authors.lastname: Orcutt
authors.forename: Anthony
authors.initials: A
authors.lastname: Scalzo
authors.forename: Eric
authors.initials: E
authors.lastname: Winer
authors.forename: Ellis
authors.initials: E
authors.lastname: Levine
authors.forename: Nasir
authors.initials: N
authors.lastname: Shahab
authors.forename: Nancy
authors.initials: N
authors.lastname: Berliner
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects*; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D015995:Prevalence; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects*; D013923:Thromboembolism / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D020845:Selective Estrogen Receptor Modulators; C095381:factor V Leiden; D013629:Tamoxifen; D005165:Factor V