AIMS: Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are associated with an increased breast cancer mortality rate in patients using tamoxifen. MATERIALS & METHODS: In the prospective population based Rotterdam study, the association between CYP2C19*2 carriers and breast cancer mortality was studied among 80 incident users of tamoxifen. Survival was analyzed with life tables and Cox regression analysis, with drug exposure as a time-dependent variable. Adjustments were made for calendar time, average tamoxifen dose, age, the indication for tamoxifen, CYP2D6 genotype and concomitant use of CYP2C19 inhibitors or inducers. RESULTS: In patients on tamoxifen, CYP2C19*2 carriers were associated with a significantly longer breast cancer survival rate than patients with the wild-type (hazard ratio 0.26, 95%CI: 0.08-0.87). CONCLUSION: This study suggests that CYP2C19 genotype may possibly be a predictive factor for survival in breast cancer patients using tamoxifen.
AIMS: Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancerpatients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are associated with an increased breast cancer mortality rate in patients using tamoxifen. MATERIALS & METHODS: In the prospective population based Rotterdam study, the association between CYP2C19*2 carriers and breast cancer mortality was studied among 80 incident users of tamoxifen. Survival was analyzed with life tables and Cox regression analysis, with drug exposure as a time-dependent variable. Adjustments were made for calendar time, average tamoxifen dose, age, the indication for tamoxifen, CYP2D6 genotype and concomitant use of CYP2C19 inhibitors or inducers. RESULTS: In patients on tamoxifen, CYP2C19*2 carriers were associated with a significantly longer breast cancer survival rate than patients with the wild-type (hazard ratio 0.26, 95%CI: 0.08-0.87). CONCLUSION: This study suggests that CYP2C19 genotype may possibly be a predictive factor for survival in breast cancerpatients using tamoxifen.
Authors: Matthew P Goetz; Katrin Sangkuhl; Henk-Jan Guchelaar; Matthias Schwab; Michael Province; Michelle Whirl-Carrillo; W Fraser Symmans; Howard L McLeod; Mark J Ratain; Hitoshi Zembutsu; Andrea Gaedigk; Ron H van Schaik; James N Ingle; Kelly E Caudle; Teri E Klein Journal: Clin Pharmacol Ther Date: 2018-01-31 Impact factor: 6.875
Authors: Tatyana A Seredina; Olga B Goreva; Valeria O Talaban; Alevtina Yu Grishanova; Vyacheslav V Lyakhovich Journal: BMC Med Genet Date: 2012-06-15 Impact factor: 2.103
Authors: K Beelen; M Opdam; T M Severson; R H T Koornstra; A D Vincent; M Hauptmann; R H N van Schaik; E M J J Berns; J B Vermorken; P J van Diest; S C Linn Journal: Breast Cancer Res Treat Date: 2013-06-05 Impact factor: 4.872
Authors: Mercedes Zafra-Ceres; Tomas de Haro; Esther Farez-Vidal; Isabel Blancas; Fernando Bandres; Eduardo Martinez de Dueñas; Enrique Ochoa-Aranda; Jose A Gomez-Capilla; Carolina Gomez-Llorente Journal: Int J Med Sci Date: 2013-05-27 Impact factor: 3.738