SAN ANTONIO--Gynecologic evaluation of women taking prophylactic tamoxifen(Drug information on tamoxifen) (Nolvadex) should be restricted to patients with endometrial thickening that exceeds 8 mm and possibly to premenopausal women with amenorrhea, a British study suggests.
Atypical hyperplasia occurred in 10 of 61 women on tamoxifen, compared with none of 50 treated with placebo. Each case of atypia was associated with endometrial thickening greater than 8 mm, Dr. Andreas Makris reported at the San Antonio Breast Cancer Symposium.
The patients constituted a subset of 111 consecutive postmenopausal women in a large randomized study of tamoxifen in women at increased risk for breast cancer. Those women taking tamoxifen had been on the therapy for at least 3 months.
The 61 women on tamoxifen also had a significantly higher uterine volume and mean endometrial thickness than those on placebo, and they had a higher incidence of endometrial proliferation and polyps (see table).
All patients in the study have one or more risks for breast cancer, said Dr. Makris, a research fellow at the Royal Marsden Hospital, London. Those randomized to tamoxifen receive 20 mg/day, and regular gynecologic assessments have been performed since 1988. To date, 2,300 patients have been enrolled, about two thirds of whom are premenopausal.
A separate analysis of all 2,300 patients revealed 88 postmenopausal women who had endometrial thickening that exceeded 8 mm: 66 on tamoxifen and 22 on placebo. A substudy of those women showed no effect from therapy to reduce endometrial thickness. The study involved 48 patients who were given norethisterone(Drug information on norethisterone) at a dose of 2.5 mg/day for 21 days in each 28-day cycle. Three courses of treatment caused no reduction in endometrial thickness in these patients, 42 of whom were on tamoxifen.
"Gynecologic evaluation of women at high risk for breast cancer who are being treated with tamoxifen should be restricted to those who have endometrial thickening of greater than 8 mm," Dr. Makris concluded. "Premenopausal women with amenorrhea who are treated with tamoxifen may also be at increased risk," he added, since they may become prematurely menopausal.