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

Abstract

Toremifene (TOR) is a valid and safe alternative to tamoxifen (TAM) for adjuvant endocrine therapy in breast cancer patients with a metabolic pathway that differs from that of TAM. TOR might have a therapeutic advantage in certain subgroups of patients, such as Chinese women with the CYP2D6 *10 (c.100C > T) T/T genotype, who would get less benefit when receiving adjuvant TAM treatment. A total of 230 breast cancer patients who received adjuvant TAM (n = 115) or TOR (n = 115) at the National Cancer Center were analyzed. The CYP2D6 *10 genotype was not significantly associated with DFS in patients who received TOR (p = 0.737). Patients treated with TOR had a higher 5-year disease-free survival (DFS) rate than those treated with TAM (89.6% vs. 80.9%, p = 0.009). TOR treatment remained an independent prognostic marker of DFS in multivariate analysis compared with TAM (hazard ratio = 0.51; p = 0.014). For all of the 50 CYP2D6 *10 T/T genotype patients, TOR treatment group had a significantly higher 5-year DFS rate than TAM group (90.9% vs. 67.9%, p = 0.031). For the remaining 170 CYP2D6 *10 C/C or C/T genotype patients, there was no significant difference between the 5-year DFS rates of the TOR and TAM groups (89.2% vs. 85.1%, p = 0.188). The advantage of adjuvant TOR over TAM in Chinese breast cancer patients might be caused by the significant benefit obtained by the CYP2D6 *10 T/T patients, who accounted for one-fifth of the overall population. TOR might be a good option for adjuvant endocrine therapy in this subgroup of patients in China.

Comparison of adverse drug reactions between tamoxifen and toremifene in breast cancer patients with different CYP2D6 genotypes: A propensity‐score matched cohort study

“…However, the 5-year DFS was significantly higher for the toremifene group than that for the tamoxifen group in IMs (90.9% vs 67.9%, P = .031) but not in EMs (89.2% vs 85.1%, P = .188). 16 In conclusion, toremifene yields superior efficacy than tamoxifen in CYP2D6 IMs. However, it had not been reported whether CYP2D6 polymorphism exerted an effect on the ADRs of these two agents.…”

“…Evidence has shown that the 5-year disease-free survival (DFS) rate is significantly higher in the toremifene-treated group than in the tamoxifen-treated group for patients with CYP2D6*10 T/T genotype, yet no significant difference exists in 5-year DFS between two treatment groups for patients carrying CYP2D6*10 C/C or C/T genotype. 16 Recent studies mainly focus on comparing tamoxifen with toremifene in terms of drug efficacy, but a research gap has always been existing in the correlation between CYP2D6 polymorphism and ADRs of these two drugs. In clinical practice, balance between efficacy and ADRs should be taken into consideration, and the need is underlined for predicting ADRs in breast cancer patients.…”

Chinese breast cancer patients with CYP2D6*10 mutant genotypes have a better prognosis with toremifene than with tamoxifen

“…T/T is a significant prognostic indicator of DFS (risk ratio [RR]: 1.87, P = .006). Additionally, in patients with a T/T genotype, DFS in TOR‐treated patients was better than that of patients in a TAM group ( P = .031) 28,29 …”

“…Additionally, in patients with a T/T genotype, DFS in TOR‐treated patients was better than that of patients in a TAM group ( P = .031). 28 , 29 …”

A prospective, randomized study of Toremifene vs. tamoxifen for the treatment of premenopausal breast cancer: safety and genital symptom analysis

“…In postmenopausal patients, TOR has been verified to have similar efficacy to that of tamoxifen as an adjuvant treatment and for metastatic disease [11][12][13][14]. In contrast to TAM, which is metabolized by cytochrome P450 enzymes, TOR is not a prodrug and has better efficacy in breast cancer patients with the CYP2D6*10 T/T genotype [15]. Data on the efficacy of TOR in premenopausal patients are limited.…”