The relationship between the CYP2D6 polymorphisms and tamoxifen efficacy in adjuvant endocrine therapy of breast cancer patients in Chinese Han population

Abstract

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.

Toremifene, rather than tamoxifen, might be a better option for the adjuvant endocrine therapy in CYP2D6*10T/T genotype breast cancer patients in China

“…We previously conducted a study to confirm this phenomenon. Our findings showed that Chinese breast cancer patients with the CYP2D6 *10 T/T genotype had worse clinical outcomes when receiving adjuvant TAM treatment …”

“…A total of 167 (21.5%) patients carried the CYP2D6 *10 T/T genotype. Among the patients who received TAM, the 5‐year DFS rate was considerably lower in CYP2D6 *10 T/T genotype patients than in C/C or C/T patients ( p = 0.007) …”

“…Among the patients who received TAM, the 5-year DFS rate was considerably lower in CYP2D6 *10 T/T genotype patients than in C/C or C/T patients (p = 0.007). 15 Propensity score matching was employed to match TAM and TOR patients for clinicopathological characteristics including age at diagnosis, tumor grade, clinical stage (AJCC 7th ed. ), adjuvant chemotherapy, adjuvant radiotherapy, and ER, PR, human epidermal growth factor receptor-2 (HER-2) status.…”

“…12 CYP2D6*10 (c.100C > T) is the most common polymorphism in Asian populations and has a frequency of 30% to 50% in Chinese populations. [13][14][15] The CYP2D6*10/ *10 genotype is associated with lower plasma concentrations of TAM active metabolites, which could influence the clinical outcome by TAM in Asian breast cancer patients. [16][17][18] We previously conducted a study to confirm this phenomenon.…”

“…Our findings showed that Chinese breast cancer patients with the CYP2D6 *10 T/T genotype had worse clinical outcomes when receiving adjuvant TAM treatment. 15 TOR, a chlorinated derivative of TAM, was developed in 1981 with the goal of achieving efficacy similar to that of TAM and with an improved safety profile. In preclinical studies, it has been shown to have equivalent ER binding and anti-tumor efficacy, with less estrogenic activity and DNA adduct formation in the endometrium.…”