- Province, M;
- Goetz, M;
- Brauch, H;
- Flockhart, D;
- Hebert, J;
- Whaley, R;
- Suman, V;
- Schroth, W;
- Winter, S;
- Zembutsu, H;
- Mushiroda, T;
- Newman, W;
- Lee, M-T;
- Ambrosone, C;
- Beckmann, M;
- Choi, J-Y;
- Dieudonné, A-S;
- Fasching, P;
- Ferraldeschi, R;
- Gong, L;
- Haschke-Becher, E;
- Howell, A;
- Jordan, L;
- Hamann, U;
- Kiyotani, K;
- Krippl, P;
- Lambrechts, D;
- Latif, A;
- Langsenlehner, U;
- Lorizio, W;
- Neven, P;
- Nguyen, A;
- Park, B-W;
- Purdie, C;
- Quinlan, P;
- Renner, W;
- Schmidt, M;
- Schwab, M;
- Shin, J-G;
- Stingl, J;
- Wegman, P;
- Wingren, S;
- Zirpoli, G;
- Thompson, A;
- Jordan, V;
- Nakamura, Y;
- Altman, R;
- Ames, M;
- Weinshilboum, R;
- Eichelbaum, M;
- Ingle, J;
- Klein, T;
- Ziv, Elad;
- Wu, Alan
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.