SERMs for the treatment and prevention of breast cancer

Abstract

Tamoxifen and raloxifene are both selective estrogen receptor modulators (SERMs). The medicines can block estrogen mediated breast cancer growth and development but will also maintain bone density in postmenopausal women and lower circulating cholesterol. Tamoxifen has remained the antihormonal therapy of choice for the treatment of ER positive breast cancer for the last 30 years. However, although adjuvant tamoxifen produces profound increases in disease-free and overall survival in patients with ER positive breast cancer, concerns about drug resistance, blood clots and endometrial cancer have resulted in a change to the use of aromatase inhibitors for the treatment of postmenopausal women. Nevertheless, tamoxifen remains the antihormonal treatment of choice for premenopausal women with ER positive breast cancer and for risk reduction in premenopausal women who are at high risk for developing breast cancer. The risk of endometrial cancer and thromboembolic disorders during tamoxifen therapy is not elevated in premenopausal women. It is important to note that aromatase inhibitors or raloxifene should not be used in premenopausal women. Raloxifene is used to prevent osteoporosis in postmenopausal women and, unlike tamoxifen, does not increase the risk of endometrial cancer. However, raloxifene does reduce breast cancer risk by 50-70% in both low risk and high risk postmenopausal women. Comparisons of raloxifene with tamoxifen show equal efficacy as a chemopreventive for breast cancer but there is a reduction in thromboembolic disorders, fewer endometrial cancers, hysterectomies, cataracts and cataract surgeries in women taking raloxifene. Overall, SERMs continue to fulfill their promise as appropriate medicines that target specific populations for the treatment and prevention of breast cancer.