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

Abstract

Purpose: To evaluate the prognosis of estrogen receptor-positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy. Methods:Estrogen receptor-positive breast cancer patients were selected and CYP2D6*10 genotypes (C/C, C/T, and T/T) were determined by Sanger sequencing.Patients were divided into tamoxifen, toremifene, or tamoxifen + toremifene groups according to prior therapy. The correlation between CYP2D6*10 genotype and diseasefree survival was analyzed. Results:In total, 293 estrogen receptor-positive breast cancer patients treated with tamoxifen or toremifene between 2008 and 2017 were studied. Median follow-up was 39 months (10-141). Of these, 107 (36.52%), 112 (38.23%), and 74 (25.26%) patients had C/C, C/T, and T/T genotypes, respectively. Genotype was significantly associated with disease-free survival in tamoxifen patients. Patients with C/T and T/T genotypes showed worse disease-free survival than patients with a C/C genotype. Genotype and disease-free survival in toremifene and tamoxifen+toremifene patients were not correlated. Of patients with a C/T genotype, toremifene or tamoxifen+toremifene groups showed better disease-free survival than tamoxifen patients. Although disease-free survival of patients with a T/T genotype in the three groups was not statistically different, tamoxifen patients showed worse disease-free survival. There was no correlation between different treatments and disease-free survival in patients with a C/C genotype. Cox proportional hazard analysis revealed toremifene patients had a better prognosis than tamoxifen patients; toremifene was an independent protective factoremifene for disease-free survival.

Oestrogen receptor positive breast cancer and its embedded mechanism: breast cancer resistance to conventional drugs and related therapies, a review

“…Hence, toremifene, a chlorinated derivative of tamoxifen, where one of the hydrogen atoms in the ethyl side chain is replaced with a chlorine atom [42], was developed in 1981 with the goal of having similar efficacy to tamoxifen and a safer profile. Also, toremifene showed better results in patients with the CYP2D6 mutation as well as in patients suffering from fatty liver and liver fibrosis [43,44]. It was approved by the FDA in 1997 for ER+ post-menopausal women [45].…”