Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial.
BACKGROUND
Tamoxifen, a selective estrogen-receptor modulator, increases venous thromboembolic events (VTE), but the factors explaining this risk are unclear. Atherosclerosis may induce VTE, or the 2 conditions may share common risk factors. We assessed the effect of tamoxifen on VTE in a breast cancer prevention trial and studied its association with risk factors for VTE.


RESULTS
The incidence of VTE was studied in 5408 hysterectomized women randomly assigned to tamoxifen 20 mg/d or placebo for 5 years. There were 28 VTEs on placebo and 44 on tamoxifen therapy (hazard ratio [HR]=1.63; 95% confidence interval [CI], 1.02 to 2.63), 80% of which were superficial phlebitis, accounting for all of the excess due to tamoxifen within 18 months from randomization. Compared with placebo, the risk of VTE on tamoxifen was higher in women aged 55 years or older, women with a body mass index > or =25 kg/m2, elevated blood pressure, total cholesterol > or =250 mg/dL, current smoking, and a family history of coronary heart disease (CHD). Of the 685 women with a CHD risk score > or =5 who entered the trial, 1 in the placebo arm and 13 in the tamoxifen arm developed VTE (log-rank P=0.0013). In multivariate regression analysis, age > or =60 years, height > or =165 cm, and diastolic blood pressure > or =90 mm Hg had independent detrimental effects on VTE risk during tamoxifen therapy, whereas transdermal estrogen therapy concomitant with tamoxifen was not associated with any excess of VTE (HR=0.64; 95% CI, 0.23 to 1.82).


CONCLUSIONS
Women with conventional risk factors for atherosclerosis have a higher risk of VTE during tamoxifen therapy. This information should be incorporated into counseling women on its risk-benefit ratio, particularly in the prevention setting.
Decensi
Andrea
A
Divisions of Chemoprevention, European Institute of Oncology, Milan, Italy. andrea.decensi@ieo.it
Maisonneuve
Patrick
P
Rotmensz
Nicole
N
Bettega
Donato
D
Costa
Alberto
A
Sacchini
Virgilio
V
Salvioni
Alessandro
A
Travaglini
Roberto
R
Oliviero
Pasquale
P
D'Aiuto
Giuseppe
G
Gulisano
Marcella
M
Gucciardo
Giacomo
G
del Turco
Marco Rosselli
MR
Pizzichetta
Maria Antonietta
MA
Conforti
Serafino
S
Bonanni
Bernardo
B
Boyle
Peter
P
Veronesi
Umberto
U
D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications / Q000517:prevention & control*; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000150:complications / Q000453:epidemiology*; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use; D020246:Venous Thrombosis / Q000150:complications / Q000453:epidemiology*
D016588:Anticarcinogenic Agents; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen