Use of tamoxifen for breast cancer: Twenty-eight years later

Abstract

Purpose: The mechanisms of antitumor activity, clinical pharmacology, toxicity, and efficacy of tamoxifen in women with early and advanced breast cancer and the drug's potential role in prevention of breast cancer were reviewed. Design: A comprehensive review of the literature from 1966 to 1994 was conducted; reports were identified using the Cancerline and Medline data bases. Results: The cellular actions of tamoxifen are not completely understood, but it appears that the drug's antiproliferative effects are mediated primarily by inhibition of the activities of estrogen through binding to estrogen receptors (ERs). Disease-free and overall survival rates have been increased in postmenopausal women with ER-positive tumors when tamoxifen has been used as adjuvant therapy (irrespective of nodal status). In premenopausal women, adjuvant therapy with tamoxifen has been associated with prolongation of disease-free survival, but its impact on survival remains to be defined. Tamoxifen is the initial hormonal treatment of choice in both premenopausal and postmenopausal women with ER-positive metastatic disease. Retrospective review of adjuvant therapy studies showed an approximately 39% reduction in the incidence of contralateral primary breast carcinoma in tomoxifen-treated women, which indicates that tamoxifen could have a role in breast cancer prevention. Conclusion: The use of tomoxifen has resulted in a substantial modification of breast cancer's natural history, particularly in postmenopausal women. Ongoing clinical trials will examine the effects of tamoxifen therapy on lipids, coagulation proteins, bone, and endometrium, and its effectiveness as an agent in the prevention of breast cancer.