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Chemoprevention of Breast Cancer: Tamoxifen, Raloxifene, and Beyond

Bao, Ting; Prowell, Tatiana; Stearns, Vered*

American Journal of Therapeutics: July-August 2006 - Volume 13 - Issue 4 - p 337-348
Therapeutic Reviews
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Breast cancer is the most common cancer and the second most common cause of cancer death among women in the United States. While nonrandomized studies have reported that prophylactic mastectomy or oophorectomy can significantly reduce the risk of breast cancer, these approaches are unacceptable to the majority of women. Chemoprevention, which is defined as the prevention of cancer by pharmacological agents that inhibit or reverse the process of carcinogenesis, has thus increasingly become the focus of breast cancer prevention efforts. The first-generation selective estrogen receptor modulator (SERM) tamoxifen is the only US Food and Drug Administration– approved drug for breast cancer prevention and reduces the risk of breast cancer by as much as 50% in high-risk women. Raloxifene, a second-generation SERM, also has demonstrated efficacy for breast cancer prevention and is being compared with tamoxifen in a large randomized trial that has recently completed accrual. The aromatase inhibitors (AIs) decrease the incidence of contralateral breast cancer when used in the adjuvant setting and are being evaluated in ongoing primary prevention studies. In addition, a number of novel agents, including antiinflammatory drugs and retinoid derivatives, which appear to be of promise based on preclinical and epidemiological data, are under investigation. Several important challenges remain, including determination of the appropriate dose and duration of treatment when used in the primary prevention setting and development of new research models using surrogate end points for breast cancer incidence and mortality to permit more rapid clinical application of promising new agents.

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland

Dr Prowell is supported by an American Society of Clinical Oncology Young Investigator Award and a Pearl M. Stetler Research Fund Award. Dr Stearns is supported in part by a Damon Runyon-Lilly Clinical Investigator Award CI-3 from the Damon Runyon Cancer Research Foundation.

*Address for correspondence: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Room 1M53, Baltimore, MD 21231-1000. E-mail: vstearn1@jhmi.edu

© 2006 Lippincott Williams & Wilkins, Inc.