Influence of CYP2D6-genotype on tamoxifen efficacy in advanced breast cancer

Karle, Jennifer; Bolbrinker, Juliane; Vogl, Silvia; Kreutz, Reinhold; Denkert, Carsten; Eucker, Jan; Wischnewsky, Manfred; Possinger, K.; Regierer, Anne C.

doi:10.1007/s10549-013-2565-3

Cited by 26 publications

(25 citation statements)

References 52 publications

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“…Poor metabolizers showed a significantly worse overall survival, a condition that was also observed in the subset analysis considering only CYP2D6*4, especially in BRCA2 carriers [16] . Karle et al [17] analysed the effect of the CYP2D6 genotyping in a palliative setting, enrolling 88 patients with ER positive advanced breast cancer. Co-medication with known CYP2D6 inhibitors was an exclusion criterion.…”

Section: Researchmentioning

confidence: 99%

“…Allele *4 was the most frequent non-functional variant, being detected in 37 cases. The authors concluded that CYP2D6 testing in advanced breast cancer is reasonable, especially if administration of tamoxifen is considered [17] . A retrospective genetic analysis of patients pooled from the Austrian prospective TIGER study, incorporated 493 women with ER positive tumours and focused exclusively in allele *4.…”

Section: Researchmentioning

confidence: 99%

“…August 10, 2014|Volume 5|Issue 3| WJCO|www.wjgnet.com Goetz et al [8] RFS DFS OS NS (P = 0.075) NS (P = 0.097) NS Worse (P = 0.005) Worse (P = 0.008) NS Scroth et al [9,10] RR MR [12] DFS 118 mo 114 mo 98 mo Bijl et al [13] RBCM NS Increased (P = 0.041) Newman et al [16] OS Worse Karle et al [17] PFS 14 mo 9 mo Abraham et al [20] BCSS NS Nowell [23] BCR, OS NS NS Rae et al [25] RR NS NS Regan et al [26] BCE prospective multicenter randomised trial (Austrian Breast and Colorectal Study 8 -ABCSG trial 8) have been newly published. In this cohort 3901 postmenopausal patients with resected ER+ early cancer were randomised to receive either five years tamoxifen or two years tamoxifen followed by anastrazole administration over three more years.…”

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Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Markopoulos

Kykalos

Mantas

2014

WJCO

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Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: CYP2D6; Tamoxifen; Breast cancer; Adjuvant treatment Core tip: Currently, routine cytochrome P450 (CYP)2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome.Markopoulos C, Kykalos S, Mantas D. Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen.

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Section: Researchmentioning

confidence: 99%

Section: Researchmentioning

confidence: 99%

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Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Markopoulos

Kykalos

Mantas

2014

WJCO

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“…Общая выживаемость была существенно ниже для группы пациентов с неактивными аллелями (IMs, PMs) по сравнению с группой EMs. Общая 5-летняя выжи-ваемость составила 76,3 % в группе EMs и 45,8 % в группах IMs и PMs [44].…”

Section: Introductionunclassified

Pharmacogenetic testing of allelic variants of the CYP2D6 gene in hormone positive breast cancer

Любченко¹,

Filippova²,

Шендрикова³

et al. 2017

Usp. mol. onkol

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“…The association of CYP2D6 gene polymorphisms with the efficacy of tamoxifen in early-stage breast cancer patients has been assessed by numerous studies, whose results were conflicting. Certain studies have shown no alterations in the efficacy of tamoxifen in breast cancer patients carrying the CYP2D6 gene polymorphism in terms of recurrence and overall survival (8,10,13), while other studies have demonstrated a significant influence of CYP2D6 gene polymorphisms on the efficacy of tamoxifen (14,15). Only one previous study has evaluated the effects of CYP2D6 gene polymorphisms on the efficacy of tamoxifen in a Brazilian population (13).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Influence of CYP2D6-genotype on tamoxifen efficacy in advanced breast cancer

Cited by 26 publications

References 52 publications

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Pharmacogenetic testing of allelic variants of the CYP2D6 gene in hormone positive breast cancer

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

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