Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 143, Issue 1, Pages 184-189Publisher
WILEY
DOI: 10.1002/ijc.31291
Keywords
breast cancer; TAM; CYP2D6; SNP; survival
Categories
Funding
- CAMS Initiative for Innovative Medicine [CAMS-12M-1-010, 2017-I2M-3-004]
- Major Project of Beijing Municipal Science and Technology Commission [D161100000816004]
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Variants of the CYP2D6 gene may lead to a poor prognosis of tamoxifen (TAM)-treated patients. Our study validated the association between the CYP2D6 genotype and outcomes of patients receiving TAM in adjuvant endocrine therapy. A total of 778 breast cancer patients who received adjuvant TAM (n = 325) or aromatase inhibitors (AIs) (n = 453) at the National Cancer Center were analyzed. Nine single nucleotide polymorphisms (SNPs) in the CYP2D6 gene were selected from online databases. The associations of each SNP genotype with disease-free survival (DFS) and clinicopathological characteristics were analyzed. A total of 167 (21.5%) patients carried the CYP2D6*10 (c.100C>T) T/T genotype. Among the 325 patients who received TAM, the 5-year DFS rate was considerably lower in CYP2D6*10 T/T genotype patients than C/C or C/T patients (54.9% vs. 70.9%, p = 0.007). The T/T genotype for CYP2D6*10 was a significant prognostic marker for DFS in multivariate analysis (hazard ratio = 1.87; p = 0.006). The CYP2D6*10 genotype in women who received AIs was not significantly associated with DFS (p = 0.332). Other SNPs were not related to the survival of patients who received TAM. Our finding showed patients with CYP2D6*10 T/T received less benefit from TAM adjuvant treatment. This conclusion may optimize the individualized treatments for this subgroup of patients.
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