Low-dose tamoxifen attenuates risk biomarkers in HRT users

October 3, 2007

NEW YORK (Reuters Health) - Tamoxifen at low doses favorably modulates biomarkers of breast cancer and cardiovascular risk in women who use hormone replacement therapy (HRT) without increasing endometrial proliferation or menopausal symptoms, according to a study published in the September issue of the Journal of Clinical Oncology.

"Different observations suggest that the combination HRT and tamoxifen may retain the benefits while reducing the risks of either agent," Dr. Andrea Decensi, of Ospedali Galliera, Genoa, Italy, and colleagues write.

The researchers conducted a clinical trial to measure changes plasma levels of the cancer biomarker insulin-like growth factor (IGF-1) at 12 months and to identify the optimal dose and schedule for tamoxifen in women using HRT. Biomarkers of cardiovascular disease, bone fracture, and menopausal symptoms were also assessed.

Two hundred ten HRT users younger than 60 years old were randomized to tamoxifen at 1 mg/day and placebo/week; placebo/day and tamoxifen 10 mg/week; tamoxifen 5 mg/day and placebo/week; or placebo/day and placebo/week. The 205 subjects with full sets of data were assessed at baseline, 6 and 12 months.

IGF-1 levels were significantly reduced with tamoxifen compared with placebo after 12 months (p = 0.005). The greatest reduction was observed with tamoxifen at 5 mg/day. Compared to placebo, tamoxifen increased IGF binding protein-3 and lowered antithrombin III, C reactive protein and mammographic density.

"Tamoxifen increased endometrial thickness but not Ki-67 expression, which was lower on 5 mg/day among the three doses," the researchers added.

Tamoxifen did not significantly worsen menopausal symptoms. However, there was a trend to more hot flashes, sweating, and vaginal discharge with tamoxifen.

A large phase III trial is currently underway in which HRT users are receiving 5 mg/day of tamoxifen vs. placebo to verify the efficacy of this regimen.