CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen.
OBJECTIVE
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.


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).


CONCLUSIONS
This study suggests that CYP2C19 genotype may possibly be a predictive factor for survival in breast cancer patients using tamoxifen.
Department of Epidemiology, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Rikje
R
Ruiter
Monique J
MJ
Bijl
Ron H N
RH
van Schaik
Els M J J
EM
Berns
Albert
A
Hofman
Jan-Willem W
JW
Coebergh
Charlotte
C
van Noord
Loes E
LE
Visser
Bruno H Ch
BH
Stricker
D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D013629:Tamoxifen / Q000627:therapeutic use*
D013629:Tamoxifen; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19