Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer.

Abstract

The selective estrogen-receptor modulator (SERM) tamoxifen became the first U.S. Food and Drug Administration (FDA)-approved agent for reducing breast cancer risk but did not gain wide acceptance for prevention, largely because it increased endometrial cancer and thromboembolic events. The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR). Raloxifene caused less toxicity (versus tamoxifen), including reduced thromboembolic events and endometrial cancer. In this report, we present an updated analysis with an 81-month median follow-up. STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. The risk ratio (RR; raloxifene:tamoxifen) for invasive breast cancer was 1.24 (95% confidence interval [CI], 1.05-1.47) and for noninvasive disease, 1.22 (95% CI, 0.95-1.59). Compared with initial results, the RRs widened for invasive and narrowed for noninvasive breast cancer. Toxicity RRs (raloxifene:tamoxifen) were 0.55 (95% CI, 0.36-0.83; P = 0.003) for endometrial cancer (this difference was not significant in the initial results), 0.19 (95% CI, 0.12-0.29) for uterine hyperplasia, and 0.75 (95% CI, 0.60-0.93) for thromboembolic events. There were no significant mortality differences. Long-term raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease, with far less toxicity (e.g., highly significantly less endometrial cancer). These results have important public health implications and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer.

• Authors: Victor G Vogel, Joseph P Costantino, D Lawrence Wickerham, Walter M Cronin, Reena S Cecchini, James N Atkins, Therese B Bevers, Louis Fehrenbacher, Eduardo R Pajon, James L Wade 3rd, André Robidoux, Richard G Margolese, Joan James, Carolyn D Runowicz, Patricia A Ganz, Steven E Reis, Worta McCaskill-Stevens, Leslie G Ford, V Craig Jordan, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 3 Issue 6 Pg. 696-706 (Jun 2010) ISSN: 1940-6215 [Electronic] United States
• PMID: 20404000 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
• Copyright: 2010 AACR.

Chemical References

• Estrogens
• Selective Estrogen Receptor Modulators
• Tamoxifen
• Raloxifene Hydrochloride

Topics

• Adenocarcinoma (epidemiology, pathology, prevention & control)
• Adult
• Aged
• Aged, 80 and over
• Breast Neoplasms (epidemiology, pathology, prevention & control)
• Cataract (chemically induced, epidemiology)
• Double-Blind Method
• Drug Utilization
• Endometrial Neoplasms (chemically induced, epidemiology)
• Estrogens
• Female
• Follow-Up Studies
• Fractures, Spontaneous (epidemiology, etiology, prevention & control)
• Humans
• Incidence
• Middle Aged
• Myocardial Ischemia (epidemiology, prevention & control)
• Neoplasm Invasiveness
• Neoplasms, Hormone-Dependent (epidemiology, pathology, prevention & control)
• Osteoporosis, Postmenopausal (complications, prevention & control)
• Raloxifene Hydrochloride (adverse effects, pharmacology, therapeutic use)
• Risk
• Selective Estrogen Receptor Modulators (adverse effects, pharmacology, therapeutic use)
• Tamoxifen (adverse effects, pharmacology, therapeutic use)
• Thromboembolism (chemically induced, epidemiology)
• Uterus (pathology)