Endocrine prevention of breast cancer using selective oestrogen receptor modulators (SORMs)

Breast cancer remains the most common malignancy in women worldwide. Oestrogen levels appear to be associated with an increased risk for the development of breast cancer. The Early Breast Cancer Trialists' Cooperative Group reported in a 1998 meta-analysis of 37000 breast cancer patients in 55 randomized adjuvant trials that tamoxifen, a selective oestrogen receptor modulator, reduced the incidence of contralateral breast cancers by 47% at 5 years. Tamoxifen has been shown in numerous prevention studies to decrease the incidence of breast cancer in high-risk women. Overall, the tamoxifen prevention trials showed a 38% reduction in the incidence of breast cancer (95% CI 28-46; P<0.0001). In the largest risk-reduction trial, the Breast Cancer Prevention Trial conducted by the National Surgical Adjuvant Breast and Bowel Project, tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<0.00001), and non-invasive breast cancer by 50% (P<0.002). The occurrence of oestrogen receptor-(OR)-positive tumours decreased by 69%. Tamoxifen reduces the risk of developing oestrogen receptor-positive tumours, but OR-negative tumours are not affected. Rare but life-threatening side-effects of tamoxifen include endometrial carcinoma, thromboembolic events and cerebrovascular events. Less serious side-effects include cataracts, vasomotor instability, nausea and vaginal discharge. Raloxifene, a second-generation selective oestrogen receptor modulator, is approved for treatment of osteoporosis in post-menopausal women in the USA but it is not currently approved for breast cancer prevention outside of a clinical trial. Prevention studies involving raloxifene and aromatase inhibitors are currently being conducted.