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The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial

Victor G. Vogel, MD, MHS; Joseph P. Costantino, DrPH; D. Lawrence Wickerham, MD; Walter M. Cronin, MPH; Reena S. Cecchini, MS; James N. Atkins, MD; Therese B. Bevers, MD; Louis Fehrenbacher, MD; Eduardo R. Pajon Jr, MD; James L. Wade III, MD; André Robidoux, MD; Richard G. Margolese, MD, CM; Joan James, PA-C; Scott M. Lippman, MD; Carolyn D. Runowicz, MD; Patricia A. Ganz, MD; Steven E. Reis, MD; Worta McCaskill-Stevens, MD; Leslie G. Ford, MD; V. Craig Jordan, PhD, DSc; Norman Wolmark, MD; for the National Surgical Adjuvant Breast and Bowel Project (NSABP)

JAMA. 2006;295:2727-2741. Published online June 5, 2006 (doi:10.1001/jama.295.23.joc60074).

Context  Tamoxifen is approved for the reduction of breast cancer risk, and raloxifene has demonstrated a reduced risk of breast cancer in trials of older women with osteoporosis.

Objective  To compare the relative effects and safety of raloxifene and tamoxifen on the risk of developing invasive breast cancer and other disease outcomes.

Design, Setting, and Patients  The National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial, a prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America, with final analysis initiated after at least 327 incident invasive breast cancers were diagnosed. Patients were 19 747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk (mean risk, 4.03% [SD, 2.17%]). Data reported are based on a cutoff date of December 31, 2005.

Intervention  Oral tamoxifen (20 mg/d) or raloxifene (60 mg/d) over 5 years.

Main Outcome Measures  Incidence of invasive breast cancer, uterine cancer, noninvasive breast cancer, bone fractures, thromboembolic events.

Results  There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene (incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.82-1.28). There were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the raloxifene group (80 cases) (incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98-2.00). There were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene (RR, 0.62; 95% CI, 0.35-1.08). No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events occurred less often in the raloxifene group (RR, 0.70; 95% CI, 0.54-0.91). The number of osteoporotic fractures in the groups was similar. There were fewer cataracts (RR, 0.79; 95% CI, 0.68-0.92) and cataract surgeries (RR, 0.82; 95% CI, 0.68-0.99) in the women taking raloxifene. There was no difference in the total number of deaths (101 vs 96 for tamoxifen vs raloxifene) or in causes of death.

Conclusions  Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs.

Trial Registration  clinicaltrials.gov Identifier: NCT00003906

Author Affiliations: Magee-Womens Hospital, University of Pittsburgh School of Medicine (Dr Vogel) and Graduate School of Public Health (Dr Costantino), University of Pittsburgh, Pittsburgh, Pa; National Surgical Adjuvant Breast and Bowel Project (NSABP) Operations and Biostatistical Centers, Pittsburgh (Drs Costantino, Wickerham, and Wolmark and Mr Cronin and Ms Cecchini); Allegheny General Hospital, Pittsburgh (Drs Wickerham and Wolmark); Southeast Cancer Control Consortium, Winston-Salem, NC (Dr Atkins); University of Texas M. D. Anderson Cancer Center, Houston (Drs Bevers and Lippman); Kaiser Permanente Northern California, Vallejo (Dr Fehrenbacher); Colorado CCOP, Denver Veterans Medical Center, Denver (Dr Pajon); Central Illinois CCOP, Decatur (Dr Wade); Centre hospitalier de l’Université de Montréal, Montréal, Quebec (Dr Robidoux); Jewish General Hospital, McGill University, Montréal (Dr Margolese); Fox Chase Cancer Center, Philadelphia, Pa (Ms James and Dr Jordan); University of Connecticut Health Center, Neag Comprehensive Cancer Center, Farmington (Dr Runowicz); UCLA Schools of Public Health and Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, Calif (Dr Ganz); University of Pittsburgh, Pittsburgh (Dr Reis); and National Cancer Institute/National Institutes of Health, Bethesda, Md (Drs McCaskill-Stevens and Ford).

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