The Italian breast cancer prevention trial with tamoxifen: findings and new perspectives.
The Italian Tamoxifen Prevention Study includes 5408 healthy hysterectomized women aged 35-70 years who have been randomized to 20 mg/day of tamoxifen or placebo for 5 years. After 46 months median follow-up, an increased risk of venous vascular events (38 women on tamoxifen vs. 18 women on placebo, P = 0.0053), mainly consisting of superficial phlebitis, has been observed and 41 breast cancers have occurred (19 on tamoxifen vs. 22 on placebo, P = 0.64). However, subgroup analyses indicated a borderline significant reduction of breast cancer among women continuously on estrogen replacement therapy (ERT, mostly transdermal) and receiving tamoxifen, with 8 cases of breast cancer among 390 ERT users on placebo versus 1 case among 362 ERT users on tamoxifen (RR = 0.13, 95% CI = 0.02-1.02). Withdrawal rate (mainly due to menopausal symptoms) differed according to ERT use, with compliance being 78% and 75% at 3 and 5 years, respectively, for women who never took ERT, and 92% and 88% at 3 and 5 years, respectively, for women not on ERT at baseline, but who took ERT at some time during the trial. Pharmacokinetic and pharmacodynamic (surrogate end point biomarkers) studies showed that a lower dose of tamoxifen (such as 5 mg/day) does not affect the drug's activity on several biomarkers of both cardiovascular and breast cancer risk. We are therefore planning a multicenter placebo-controlled phase III trial in postmenopausal healthy women on hormone replacement therapy (HRT) to test whether the combination of HRT and low-dose tamoxifen retains the benefits while reducing the risks of either agent maintaining a high compliance rate.
Guerrieri-Gonzaga
A
A
Division of Chemoprevention, European Institute of Oncology, Milan, Italy.
Galli
A
A
Rotmensz
N
N
Decensi
A
A
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D018890:Chemoprevention; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007558:Italy; D008875:Middle Aged; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*
D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen