Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment

Abstract

In tamoxifen-treated patients, women with the CYP2D6 *10 T/T genotype have a lower 4OHtam level in the serum and a worse clinical outcome.

The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review.

“…The majority (n = 12) of cohorts 41,73,83,87,93,96,97,[99][100][101]113,114 presented the rationale for the alleles tested for, with all but two 49,112 providing rationale for CYP2D6 per se. All described the test used for genotyping and/or the specific procedure, with TaqMan or AmpliChip being the most commonly used in 12 83 reported quality control methods and seven cohorts 87,91,96,97,104,114 reported on the Hardy-Weinberg equilibrium (two of these cohorts were reported in the same paper 114 ).…”

“…In around half (n = 12) of the cohorts it was clear there were missing genotype data, 41,82,83,87,[96][97][98][99][100][101]108,112 reasons being provided in seven of these. 82,83,87,97,99,108,112 Only three of the cohorts, all abstracts, 86,90,113 failed to present the number of patients contributing to each analysis.…”

“…49,73,87,104,[112][113][114] All other studies were analysed retrospectively, using archived samples. In five cohorts, 92,96,100,101,112 alongside data on patients receiving TAM, additional comparative data were provided for patients not receiving TAM. 83 although, where average duration data were provided, all retrospective analyses were of at least 5 years' duration.…”

Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia

“…Recent studies have shown that CYP2D6*10 genotype affects the efficacy of tamoxifen treatment in Chinese women with breast cancer, although women with the CYP2D6*10 variant homozygous variant allele (T/T) genotype have a worse clinical outcome (Xu et al, 2008). Other studies have shown that giving tamoxifen citrate alone exerts a limited effect on sperm morphology and motility; it appears that the superior functional sperm fraction response was probably related to administration of testosterone undecanoate (Adamopoulos et al, 1997;.…”

Genetic polymorphisms of CYP2D6*10 and CYP2C19*2, *3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen

“…Compared with CYP2D6 extensive metabolizers, poor metabolizers exhibit a 3-fold higher risk of recurrence, 2,3 whereas CYP2D6 intermediate metabolizers (those with ''intermediate'' reductions in endoxifen concentrations) exhibit a lower risk of recurrence. [2][3][4][5] Given the characteristics of the study by Okishiro et al (median follow-up, 56 months among 173 patients, with 25% with the *10/*10 genotype; enrollment period, 6 years; follow-up, 4 years; and 5-year recurrence-free survival rate, 90% in the *10/*10 genotype subgroup), a 2-sided a ¼ .05 logrank test has a power of 26% to detect a 2-fold increase in the hazard of disease recurrence in the *10/*10 carriers relative to *10/wild type (wt) or wt/wt carriers.…”