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Notes: Abstract: The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1075122X:TBJ20098:ges" location="ges.gif"/〉35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p 〈 0.00001). Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided p 〈 0.002). In addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had no effect on the rate of ischemic heart disease. As previously shown, the rates of endometrial cancer and vascular events increased with tamoxifen. With the P-1 results establishing tamoxifen as the standard of care for the primary chemoprevention of breast cancer in high-risk women, concern over the side effects of tamoxifen has prompted a continuing search for an agent that displays a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM approved for the prevention of osteoporosis in postmenopausal women, displays antiestrogenic properties in the breast and possibly the endometrium, and estrogenic effects in the bone and on the lipid profile, suggesting it as a candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in North America. The plan is to randomize 22,000 postmenopausal women 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1075122X:TBJ20098:ges" location="ges.gif"/〉35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events.

Notes: PROCEEDINGS OF THE SOCIETY

Notes: Abstract This paper outlines an approach to studying productivity in clinical research programs that incorporates environmental, organizational, provider, and patient specific factors in the model of production process. We describe how this approach has been applied to the National Cancer Institute's (NCI) Community Clinical Oncology Programs (CCOPs). Next, a practical evaluative model of the productive process in CCOPs is outlined and its use in evaluation and monitoring performance in CCOPs is discussed. Each level of the model is described and a number of factors potentially affecting each level are explored. Finally, we discuss the strengths and weaknesses of this approach and show how management can use it to study and improve the productivity of clinical research programs.

Notes: Abstract The evaluation of programs with multiple, and potentially conflicting, goals requires the integration of measures of goal achievement that often are not easily combined. One approach is the development of analytical themes which span the various goals of a particular program. The themes provide a mechanism by which the policy concerns of individuals with varying perspectives can be integrated into the evaluation framework. As well, the themes allow for flexibility in the development of new analysis as the program matures and environments change. This paper describes the application of the thematic approach to the evaluation of a complex, community-oriented cancer research program.