Update of the National Surgical Adjvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing Breast Cancer

• Published in: Cancer prevention research (Philadelphia, Pa.) Vol. 3; no. 6; pp. 696 - 706
• Main Authors: Vogel, Victor G., Costantino, Joseph P., Wickerham, D. Lawrence, Cronin, Walter M., Cecchini, Reena S., Atkins, James N., Bevers, Therese B., Fehrenbacher, Louis, Pajon, Eduardo R., Wade, James L., Robidoux, Andre, Margolese, Richard G., James, Joan, Runowicz, Carolyn D., Ganz, Patricia A., Reis, Steven E., McCaskill-Stevens, Worta, Ford, Leslie G., Jordan, V. Craig, Wolmark, Norman
• Format: Journal Article
• Language: English
• Published: 19.04.2010
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.CAPR-10-0076

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, including reduced thromboembolic events and endometrial cancer. In this paper, we detail a longer-term analysis of STAR (median follow-up of 81 months vs 47 months in the initial report). We performed this updated analysis in an effort to better understand how these two drugs differ, particularly in regard to their relative effects on noninvasive disease. STAR eligibility criteria included postmenopausal status and 5-year breast cancer risk of at least 1.66% (actual mean risk was 4.03%). STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. Of the originally randomized 19,747 women, 19,490 participated in the STAR follow-up described here. 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 was 1.22 (95% CI, 0.95–1.59). Compared with the 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. These updated data should encourage widespread acceptance of raloxifene and a greater acceptance of tamoxifen for breast cancer risk reduction.