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139th National Cancer Advisory Board

disease, endometrial cancer, ischemic heart disease, and fractures. Of the 184,000 women screened for this study, 96,000 were found to be risk-eligible and 20,000 were randomized over a 5-year period. Dr. Wickerham attributed the success of P-2 STAR to the rigorous screening process in which all individuals received an individualized risk/benefit estimate based on the Gail model and discussion about breast cancer and screening.

Characteristics of the STAR population were: (1) age distribution—9 percent under age 50, 50 percent in their 50s, 32 percent in their 60s, and 9 percent above age 70; (2) racial/ethnic distribution— 93.5 white and 6.5 minority; (3) 5-year predicted Gail scores—25 percent with a 5 percent or greater risk, with an average score of more than 4 percent; (4) 70 percent with one or more first-degree relatives with breast cancer; (5) 51.5 percent with prior hysterectomy; and (6) compared with BCPT-P1, an increase in the percentage of LCIS and atypical hyperplasia (more than 22 percent of the women with atypia). Dr. Wickerham presented the overall results of the STAR trial showing that tamoxifen and raloxifene were equally effective in reducing the risk of invasive breast cancer by approximately 50% from an estimated 8/1000/year to 4/1000/year. The cancers that did occur in the tamoxifen or raloxifene groups were of equivalent size, stage, receptor, and nodal status. Raloxifene was not as effective as tamoxifen in reducing the incidence of non-invasive breast cancers (DCIS and LCIS combined), but raloxifene-treated women had fewer deep vein thrombosis, pulmonary emboli, cataracts, endometrial cancers, and hysterectomies for benign disease. He noted that Quality of Life (QOL) was monitored closely in this population, and there were no significant differences in the primary QOL endpoints and overall minimal symptom severity across the board. In summary, raloxifene was demonstrated to be as effective as tamoxifen in the prevention of primary invasive breast cancer, but less effective in the prevention of noninvasive disease (LCIS and DCIS combined). Compared with tamoxifen, raloxifene use was demonstrated to result in fewer thromboembolic events, fewer endometrial cancers, and fewer cataracts. This analysis was based on 76,000 patient years or followup, just short of 4 years on average.

Dr. Wickerham observed that, as a result of P-2 STAR, postmenopausal women at increased risk for this disease now have a new, effective option for breast cancer prevention and one that comes with fewer serious side effects. The option also is an attractive one inasmuch as there are 500,000 women in the United States today on this medication for the treatment and prevention of osteoporosis; those women tend to be older and tend to have a lower breast cancer risk than the group in the STAR trial, and they already are receiving the benefits relative to breast cancer risk reduction. Dr. Wickerham noted estimates that breast cancer has been prevented in as many 10,000 to 14,000 women of that 500,000. Moreover, primary care providers are comfortable prescribing raloxifene and know what to expect. He predicted that, if the FDA approves raloxifene for this indication, broader use of it will be seen for primary breast cancer prevention.

Dr. Wickerham itemized other benefits already leveraged by both BCPT-P1 and P-2 STAR: (1) serum and lymphocytes on more than 30,000 of these women have been stored from the baseline exams; (2) formalin-fixed tumor blocks have been banked, not only of their breast cancers but also their endometrial and other cancers; and (3) access to these is not restricted to NSABP investigators; an open process allows that to occur across the board and the availability has been promoted through the various breast and GI SPOREs, as well as to the general scientific community.

Dr. Wickerham observed that P-2 STAR is an important step and, although much progress has been made since 1990 with the BCPT-P1, P-2 STAR, and Women’s Health Initiative, there clearly is more work to be done. True to its history of doing trials that build on the results of prior studies, the NSABP has proposed the P4 trial, a study of letrozole and raloxifene. Members were reminded that the aromatase inhibitors (AIs) are rapidly replacing tamoxifen in the adjuvant treatment of receptor-positive postmenopausal women. In those large adjuvant trials, the AIs on average have reduced the risk of new


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