Uterine side effects of tamoxifen: a need for systematic pretreatment screening

To determine the effect of tamoxifen on the endometrium in postmenopausal women with breast cancer and to try to identify, by pretreatment screening, subjects at higher risk of developing endometrial cancer.

Between January 1993 and January 1996, 264 postmenopausal women with breast cancer were studied prospectively with pelvic ultrasonography. Outpatient hysteroscopy and endometrial biopsy were done if ultrasound abnormalities were detected. Initial endometrial evaluation was done before treatment with tamoxifen was started, 20 mg daily, and annually thereafter. Attention was focused on endometrial lesions and, especially, endometrial hyperplasia, which was defined according to World Health Organization classification. Endometrial hyperplasia was subdivided into two broad categories: hyperplasia without cytological atypia and hyperplasia with cytological atypia. Adenocarcinoma in situ was defined as a well-differentiated endometrial carcinoma confined to the endometrial mucosa without myometrial invasion.

Forty-six women (17.4%) had asymptomatic endometrial lesions diagnosed before starting tamoxifen, and two of these were atypical lesions. Patients with initial lesions and those without initial lesions were followed separately. At 3 years of follow-up, the incidence of atypical lesions was significantly higher in women with lesions initially than in those without (three lesions among nine women versus one lesion among 51 women, P = .009).

It appears that a group of high-risk subjects can be defined on the basis of endometrial evaluation before tamoxifen therapy; these women should be followed carefully because of the high incidence of severe atypical lesions.