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The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1), CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy., Funding Agencies:National Institutes of Health (National Institute of General Medical Sciences)National Institutes of Health (National Cancer Institute)National Institutes of Health (National Institute of Child Health and Human Development)Breast Cancer Research (Scotland) Tayside Tissue Bank California Breast Cancer Research Program Cancer Research UK Deutsches Krebsforschungszentrum, Heidelberg, Germany Robert Bosch Foundation, Stuttgart, Germany Marie Curie Initial Training Network "FightingDrugFailure" GrantStichting Emmanuel van der Schueren (scientific partner of the Vlaamse Liga tegen Kanker) National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea Deutsche Forschungsgemeinschaft, Germany

The Robert H. Lurie Cancer Center at Northwestern University is an NCI-funded comprehensive cancer center. The Cancer Center has made significant advances in developing a premier breast cancer program. In September, 1994, the Cancer Center received a four year award from the U.S. ARMY for comprehensive training of graduate students conducting breast cancer relevant research entitled, "Molecular Biology of Breast Neoplasia". This program has successfully trained 12 predoctoral students and 3 postdoctoral fellows, 14 of who are still actively pursuing research careers. Trainees were exposed to the latest developments in breast cancer biology and treatment. Students received laboratory training with senior basic science faculty and clinical investigators provided a translational link. Members of the program participated in a weekly Journal Club and a monthly breast cancer research meeting to augment their research training. The publication record of the trainees is indicative of the success of the Training Grant. The instruction received by the trainees puts them in an ideal position to contribute to advancements in the treatment and prevention of breast cancer.

The Robert H. Lurie Cancer Center at Northwestern University is an NCI-funded comprehensive cancer center. The Cancer Center has made significant advances in developing a premier breast cancer program. In September, 1994, the Cancer Center received a four year award from the US ARMY for comprehensive training of graduate students conducting breast cancer relevant research entitled, "Molecular Biology of Breast Neoplasia". This program exposes four students per year to the latest developments in breast cancer biology and treatment.