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Tamoxifen, Raloxifene, and the Prevention of Breast Cancer¹

Departments of Molecular Pharmacology, Biological Chemistry (V.C.J.), and Surgery (M.M.), Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611

I. Introduction

II. Lacassagne’s Prevention Principle: A Target and an Estrogen Antagonist

III. Tamoxifen as an Antitumor Agent

A. ER status and the duration of tamoxifen

B. Contralateral breast cancer

C. Endometrial cancer

D. Conclusions

IV. Selective Estrogen Receptor Modulation

A. Antiestrogen activity at the ER

B. Coactivators for ER

C. Alternate response elements on DNA

D. An alternate ER-ERß

V. Biological Basis for Tamoxifen as a Breast Cancer Preventive

A. Animal models

B. Bones

C. Lipids

D. Uterus

VI. Risk Factors for Breast Cancer

A. Interactions among risk factors

B. Identification of candidates for chemoprevention

VII. Prevention of Breast Cancer with Tamoxifen

A. Royal Marsden Pilot Study

B. NSABP/NCI Study

C. Italian study

D. Conclusions

VIII. Biological Basis for Raloxifene as a Breast Cancer Preventive

A. Antitumor actions

B. Bones

C. Lipids

D. Uterus

IX. Study of Tamoxifen And Raloxifene (STAR)

X. The Future of Prevention