Guidelines for monitoring patients taking tamoxifen treatment.

Tamoxifen is the most important anti-breast cancer drug in clinical use and has the potential to be used as a chemopreventive breast cancer agent. Using outpatient hysteroscopy and based on 2 case control and 2 cohort follow-up studies in our department, we were able to demonstrate that 50% of women receiving long term tamoxifen experienced some sort of adverse endometrial effects. Although many women retain an atrophic endometrial layer, tamoxifen intake can lead to extensive senile cystic atrophia of the human endometrium, to endometrial hyperplasia and to endometrial polyp formation. Based on a critical review of the literature, we have shown that tamoxifen doubles the risk for developing endometrial cancer in postmenopausal women, although this increased risk may be higher and is duration (i.e. time of use)-dependent. Screening patients with breast cancer for endometrial abnormalities while they are taking tamoxifen is feasible and uterine morbidity related to tamoxifen intake is preventable. Although screening may increase drug compliance it may not be cost-beneficial. However, uterine safety becomes important when only a small benefit of the treatment is to be expected as in the use of tamoxifen in healthy women for breast cancer prevention. The aim of this report is to discuss methods and guidelines for detecting endometrial adverse effects of tamoxifen and to provide the clinician with a current opinion on timing and frequency of screening patients taking tamoxifen for the development of endometrial cancer. In summary, those who advocate screening should start with pretreatment uterine assessment using transvaginal ultrasonography or outpatient hysteroscopy. Symptom-free women with a normal pretreatment uterine cavity can be screened annually with transvaginal sonography from 2 to 3 years after the start of tamoxifen. Hysteroscopy or saline infusion sonography will be required if there is endometrial thickening because the only value of transvaginal ultrasonography is a normal finding being a thin rectilinear endometrium.