Tamoxifen, screening and new oestrogen receptor modulators

Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oest rogenic properties in the breast and oestrogenic effects in tissues such as bone and the cardiovascular system. It is an excellent breast cancer drug for all stages of the disease. Its SERM profile makes it a valuable alterna tive to hormone replacement therapy, especially for women at high risk of b reast cancer. Tamoxifen, however, increases the incidence of benign and mal ignant lesions of the uterus. Secondary prevention of these, early detectio n and treatment, is feasible but not cost-effective in breast cancer patien ts because potential endometrial risks do not outweigh beneficial effects i n the breast. This may be different in healthy women with an as yet unknown benefit on breast cancer mortality. We review the literature on the importance of tamoxifen's endometrial lesio ns and balance available evidence on whether and how best to screen them. I n a subset of tamoxifen users it seems advisable to assess the uterine cavi ty prior to intake with a yearly endometrial assessment as pointed out, sta rting 3 years after initiation of treatment. In most cases there is endomet rial thickening on ultrasonographic assessment and additional tests such as hydrosonography or hysteroscopy are required to confirm an empty atrophic uterus as remains the case in most asymptomatic women on tamoxifen. Newer compounds, such as raloxifene, have a similar SERM profile to tamoxif en but are neutral on the uterus. This has recently been proven by 3 years of endometrial follow-up data. Longer endometrial safety will hopefully con firm these early findings. Whether other SERMs in development are better, a nd which of them is better for the breast, is to be demonstrated in ongoing studies.