SERMs are selective estrogen receptor modulators. Estrogens stimulate the cells to divide and grow. SERMS can mimic estrogen, which means that cells think the SERM is estrogen, and, depending on the tissue, either promote or stop estrogen effects. For example, SERMs will either stimulate a cell or block its growth. This seems to depend on which tissues are involved and which SERM is used. Tamoxifen and raloxifene are both pill medications that are SERMs, and other SERMs are in the process of being developed.


Tamoxifen (Nolvadex®, generics) was the first SERM produced, and has been in use in clinics for more than 30 years to treat breast cancer. Initially it was used to treat metastatic disease, but we know that it is effective both in reducing recurrence of primary breast cancer and improving overall survival in both postmenopausal and premenopausal women. As well, it has been shown to reduce the incidence of local recurrence of breast cancer in the contralateral (opposite) breast. Tamoxifen has been used for almost 10 years as a prevention strategy for women at a higher risk of developing breast cancer. However, it does have side effects.

Because tamoxifen is not a perfect medication, researchers have been trying to develop a SERM that will have the beneficial effects of tamoxifen without some of its negative side effects. Attempts have been made to develop a SERM that will act like estrogen where it is needed but not stimulate tissues where estrogen may be dangerous.

The ideal SERM would act like estrogen on the bones to protect against osteoporosis, as well as affect lipid and cholesterol levels to protect against heart disease. The medication would also stimulate the estrogen receptors in the brain, as there is evidence for estrogen's positive effect on memory, and it would keep skin and mucous membranes healthy.

However, there are concerns about estrogen's stimulatory effects on breast tissue and on the endometrium, which may increase the incidence of breast cancer and cancer of the uterus. Therefore, the ideal SERM would act as an anti-estrogen on those tissues and protect against cancer.


Raloxifene (Evista®, generics) is a SERM that is approved to prevent and treat osteoporosis in postmenopausal women. Raloxifene is very similar to tamoxifen and has many of the same side effects, such as hot flushes, vaginal discharge, and an increased risk of clotting resulting in strokes, pulmonary embolus, and deep vein thrombosis. It does appear that raloxifene stimulates the uterus less than tamoxifen so there may be a lower incidence of endometrial cancer.

Raloxifene is not recommended for premenopausal women. Raloxifene is a medication for osteoporosis but its role in cancer prevention needs to be assessed.

Karen Gelmon, MD 
in association with the MediResource Clinical Team