REVIEW ARTICLE Tamoxifen and Toremifene in Breast Cancer: Comparison of Safety and Efficacy

Purpose: Tamoxifen is currently the standard hor-monal treatment of breast cancer, both for metastatic disease and in the adjuvant setting. A new antiestro-gen, toremifene, was approved recently for use in managing metastatic breast cancer in postmenopausal women. Methods: Toremifene is structurally similar to tamoxi-fen, differing only by a single chlorine atom, and has a similar pharmacologic profile. The major difference be-tween 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; there-fore, 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 OVER THE NEARLY 20 YEARS since its introduction 0J in the United States, tamoxifen has become firmly established as the standard in the hormonal treatment of both early and advanced breast cancer. First approved for the treatment of advanced breast cancer in postmenopausal women, tamoxifen's indications have expanded to include advanced breast cancer in premenopausal women, in men, and as adjuvant therapy for both node-positive and node-negative disease. The uses of tamoxifen have broadened due to its efficacy in prolonging disease-free survival and reducing mortality rates, as well as a 39 % reduction in the risk for contralateral breast cancer. ' Patients with estrogen receptor (ER)-positive breast cancer seem to derive the greatest benefit from tamoxifen therapy. Recently, a variety of new antiestrogen compounds have begun to receive attention as potential successors to tamoxi-fen. One of these, toremifene, is a tamoxifen analog, differing chemically by only a single chlorine atom (Fig 1)