Tamoxifen and toremifene in breast cancer: Comparison of safety and efficacy

Purpose: Tamoxifen is currently the standard hormonal treatment of breast cancer, both for metastatic disease and in the adjuvant setting. A new antiestrogen, toremifene, was approved recently for use in managing metastatic breast cancer in postmenopausal women. Methods: Toremifene is structurally similar to tamoxifen, differing only by a single chlorine atom, and has a similar pharmacologic profile. The major difference between the two compounds is in the preclinical activity; chronic, high-dose tamoxifen is hepatocarcinogenic in the rat, whereas toremifene is not. Neither agent is hepatocarcinogenic in mice, hamsters, or humans; therefore, clinical relevance of the rat data may not be significant. Results: In a worldwide phase III trial, the two agents demonstrated comparable efficacy and safety against metastatic breast cancer. Both agents have shown a significant hypocholesterolemic effect after long-term administration. Conclusion: Due to the paucity of long-term clinical data on toremifene, important unresolved questions remain, which include its effects on bone mineral density, the frequency of cardiac events, and the risk for endometrial cancer. Tamoxifen has been associated with maintenance of bone mineral density, a reduction in cardiac events, and a slightly increased risk of endometrial cancer. Toremifene is not likely to be used as second-line therapy after tamoxifen failure due to cross-resistance, and its ultimate place in therapy of advanced breast cancer remains to be determined.