CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence

Abstract

Abstract. At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Thus, the aim of the present study was to investigate the association of the CYP2D6 *4, *10 and *17 gene polymorphisms with breast cancer recurrence in a Brazilian population. The cohort comprised 40 receptor-positive breast cancer patients without recurrence and 40 with distant recurrence. A 3-ml sample of peripheral blood was collected from each patient to determine the presence of the *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by quantitative polymerase chain reaction analysis. There was no statistically significant difference between the two groups regarding the polymorphism frequency (P=0.246). The results revealed that intermediate metabolizers occurred in 5% of patients without recurrence and in 15% of those with distant recurrence. Poor metabolizers occurred in only 1 patient (2.5%) per group, and there was no significant difference between the groups (P= 0.789). The present study concluded that the CYP2D6 gene polymorphism in women with hormone-sensitive breast cancer treated with tamoxifen was not associated with disease recurrence.

Tamoxifen and CYP2D6: A Controversy in Pharmacogenetics

“…Since the publication of our metaanalysis, using the same search criteria through November 2017 (D. P. Cronin-Fenton et al, 2013), over 20 additional published studies have investigated the impact of CYP2D6 genetic polymorphisms on breast cancer prognosis. (Argalacsova, Slanar, Bakhouche, & Pertuzelka, 2017;Chamnanphon et al, 2013;De Ameida Melo et al, 2016;Dezentje et al, 2013;Dezentje et al, 2015;Goetz et al, 2017;Hertz et al, 2017;Johansson et al, 2016;Lei et al, 2016;Marcath et al, 2017;Markkula, Hjertberg, Rose, Ingvar, & Jernstrom, 2014;Martins, Vidal, Souza, Brusaca, & Brito, 2014;Mwinyi et al, 2014;Powers et al, 2016;Sanchez-Spitman et al, 2017;Sensorn et al, 2013;Zhang et al, 2015) Most suggest little evidence of an association of the CYP2D6 *4 or *10 variant with recurrence and mortality in tamoxifen-treated breast cancer patients. Here, we provide some highlight some of these studies.…”

“…However, three recent studies suggest a correlation of CYP2D6 mutations with decreased progression-free survival in patients with advanced breast cancer. (De Ameida Melo et al, 2016;Goetz et al, 2017;Karle et al, 2013) However, the studies included fewer than 100 patients, thus estimates were imprecise. In addition, the clinical significance of investigating the association of CYP2D6 polymorphisms and prognosis in metastatic breast cancer patients remains unclear, as these patients are likely to have treatment-refractory disease.…”

Pharmacogenetic testing in oncology: a Brazilian perspective

“…Two other studies examined the frequency of selected CYP2D6 alleles on recurrence 76 and disease-free survival 77 in Brazilian women with breast cancer. Both studies included relatively small cohorts (n=80 and 58), genotyped limited numbers of known functional CYP2D6 variants and did not examine copy number variation, which collectively influenced the conclusions drawn.…”

CYP2D6*3 (A2549del), *4 (G1846A), *10 (C100T) and *17 (C1023T) genetic polymorphisms in Iranian breast cancer patients treated with adjuvant tamoxifen

“…Previous study reported the prevalence of CYP2D6*10 as ~9.0% in Iranian Azerbaijanis (26), but another study of Iranians of different ethnicities reported the prevalence of the allele to be 39.3% (24.3% for homozygous T/T and 15.0% for heterozygous C/T) (25). The frequency of CYP2D6*4 varies across different races, and frequencies of 36.6, 28.6, 28.0, 13.8, 13.8, 7.3 and 0.2% have been reported in Iranians, Malaysian Indians, Turks, Spanish subjects, Brazilians, South-Indians and North Americans, respectively (18,(36)(37)(38)(39)(40)(41). Conversely, the frequency of CYP2D6*4 varies from 0.2 to 3.5% among Japanese, Chinese and Saudi Arabians, which is considered relatively low (20)(21)(22).…”