PURPOSE: To evaluate whether breast cancer (BC) patients with CYP2D6 gene variation have different clinical tamoxifen (TAM) treatment outcomes to those with normal function of CYP2D6. METHODS: Systematic searches of the PubMed up to February 21, 2013, were retrieved. The study end points were disease-free survival (DFS) and overall survival (OS). Fixed or random-effects meta-analytical models were used to calculate summary hazard ratio (HR) and corresponding 95 % confidence intervals (CIs). Meta-regression, Galbraith plots, subgroup analysis, and sensitivity analysis were also performed. RESULTS: A total of 11,701 BC patients from 20 trials were included. Compared with reduced CYP2D6 function, normal function was associated with a trend toward improved DFS (HR = 1.37, 95 % CI 1.12-1.69, P = 0.002) and OS (HR = 1.25, 95 % CI 1.03-1.50, P = 0.021). We found significant heterogeneity between studies. When the analysis was stratified into subgroups, significantly worse DFS was found in the groups of intermediate metabolizer versus extensive metabolizer (HR = 1.65, 95 % CI 1.04-2.64, P = 0.035), Asian population (HR = 3.29, 95 % CI 1.64-6.63, P = 0.001), 5 years TAM treatment duration (HR = 1.59; 95 % CI 1.14-2.22, P = 0.006), concomitant chemotherapy (HR = 1.35, 95 % CI 1.04-1.76, P = 0.025), and TAM alone (HR = 1.44, 95 % CI 1.44-2.06, P = 0.045). With respect to OS, no significant association was demonstrated in stratified analyses. CONCLUSIONS: We concluded that CYP2D6 polymorphisms may influence tamoxifen treatment outcomes of DFS in BC patients.
PURPOSE: To evaluate whether breast cancer (BC) patients with CYP2D6 gene variation have different clinical tamoxifen (TAM) treatment outcomes to those with normal function of CYP2D6. METHODS: Systematic searches of the PubMed up to February 21, 2013, were retrieved. The study end points were disease-free survival (DFS) and overall survival (OS). Fixed or random-effects meta-analytical models were used to calculate summary hazard ratio (HR) and corresponding 95 % confidence intervals (CIs). Meta-regression, Galbraith plots, subgroup analysis, and sensitivity analysis were also performed. RESULTS: A total of 11,701 BC patients from 20 trials were included. Compared with reduced CYP2D6 function, normal function was associated with a trend toward improved DFS (HR = 1.37, 95 % CI 1.12-1.69, P = 0.002) and OS (HR = 1.25, 95 % CI 1.03-1.50, P = 0.021). We found significant heterogeneity between studies. When the analysis was stratified into subgroups, significantly worse DFS was found in the groups of intermediate metabolizer versus extensive metabolizer (HR = 1.65, 95 % CI 1.04-2.64, P = 0.035), Asian population (HR = 3.29, 95 % CI 1.64-6.63, P = 0.001), 5 years TAM treatment duration (HR = 1.59; 95 % CI 1.14-2.22, P = 0.006), concomitant chemotherapy (HR = 1.35, 95 % CI 1.04-1.76, P = 0.025), and TAM alone (HR = 1.44, 95 % CI 1.44-2.06, P = 0.045). With respect to OS, no significant association was demonstrated in stratified analyses. CONCLUSIONS: We concluded that CYP2D6 polymorphisms may influence tamoxifen treatment outcomes of DFS in BC patients.
Authors: D L Hertz; K M Kidwell; S G Hilsenbeck; S Oesterreich; C K Osborne; S Philips; C Chenault; R J Hartmaier; T C Skaar; M J Sikora; J M Rae Journal: Breast Cancer Res Treat Date: 2017-07-20 Impact factor: 4.872
Authors: Richard Sposto; Theresa H M Keegan; Cheryl Vigen; Marilyn L Kwan; Leslie Bernstein; Esther M John; Iona Cheng; Juan Yang; Jocelyn Koo; Allison W Kurian; Bette J Caan; Yani Lu; Kristine R Monroe; Salma Shariff-Marco; Scarlett Lin Gomez; Anna H Wu Journal: Cancer Epidemiol Biomarkers Prev Date: 2016-04-26 Impact factor: 4.090
Authors: Thomas P Ahern; Richard F MacLehose; Laura Haines; Deirdre P Cronin-Fenton; Per Damkier; Lindsay J Collin; Timothy L Lash Journal: BMJ Evid Based Med Date: 2020-03-27