Recent results from clinical trials using SERMs to reduce the risk of breast cancer

Abstract

Selective estrogen receptor modulators (SERMs) are used for the treatment of invasive breast cancer. Chemoprevention is the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent the progression of premalignant lesions to invasive carcinoma. The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to its use in breast cancer prevention. Four large trials have used tamoxifen, the prototypical SERM, as a breast cancer chemopreventive agent with differing results. In the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the risk of invasive breast cancer by 49%. Tamoxifen also reduced the incidence of benign breast disease as well as the number of breast biopsies in the treated women. Three other randomized prevention trials comparing tamoxifen with placebo have been reported and show a reduction in breast cancer incidence of 38%. Serum levels of estrone sulfate and testosterone are significantly associated with breast cancer risk, and estradiol appears to be more strongly associated with breast cancer in high-risk women. Raloxifene is comparable to tamoxifen in its ability to reduce the risk of breast cancer in postmenopausal, high-risk women and has fewer side effects, as shown in the study of tamoxifen and raloxifene. Several ongoing and planned studies will evaluate the ability of aromatase inhibitors to reduce the risk of breast cancer in women at increased risk.