Address for correspondence: Andrea Decensi, M.D., Director, Division of Chemoprevention, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy. Voice: +39-0257489861; fax: +39-0257489809.
andrea.decensi{at}ieo.it
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.
