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Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival.

Martins DM, Vidal FC, Souza RD, Brusaca SA, Brito LM - Braz. J. Med. Biol. Res. (2014)

Bottom Line: We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant.This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes.These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

View Article: PubMed Central - PubMed

Affiliation: Instituto Maranhense de Oncologia Aldenora Bello, São Luís, MA, Brasil.

ABSTRACT
The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. We observed a high frequency of CYP2D6 *10, with an allelic frequency of 0.14 (14.4%). The *3 allele was not present in the studied population, and *4 had an allelic frequency of 0.13 (13.8%). We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant. We also observed a high frequency of CYP2D6 *10, which had not been previously described in this specific population. This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes. These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

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Disease-free survival was estimated using the Kaplan-Meier method anddefined as the period between diagnosis and local or distant recurrence.Survival curves between phenotypic groups were compared using the log-ranktest. P=0.75, not statistically significant.
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f01: Disease-free survival was estimated using the Kaplan-Meier method anddefined as the period between diagnosis and local or distant recurrence.Survival curves between phenotypic groups were compared using the log-ranktest. P=0.75, not statistically significant.

Mentions: The study results demonstrated that patients with reduced enzyme activity did nothave shorter DFS than women with normal CYP2D6 activity (log-rank test, P=0.75; Figure 1). The only patient classified as PM didnot have local or distant recurrence; however, her use of TMX was interrupted due toendometrial thickening.


Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival.

Martins DM, Vidal FC, Souza RD, Brusaca SA, Brito LM - Braz. J. Med. Biol. Res. (2014)

Disease-free survival was estimated using the Kaplan-Meier method anddefined as the period between diagnosis and local or distant recurrence.Survival curves between phenotypic groups were compared using the log-ranktest. P=0.75, not statistically significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230293&req=5

f01: Disease-free survival was estimated using the Kaplan-Meier method anddefined as the period between diagnosis and local or distant recurrence.Survival curves between phenotypic groups were compared using the log-ranktest. P=0.75, not statistically significant.
Mentions: The study results demonstrated that patients with reduced enzyme activity did nothave shorter DFS than women with normal CYP2D6 activity (log-rank test, P=0.75; Figure 1). The only patient classified as PM didnot have local or distant recurrence; however, her use of TMX was interrupted due toendometrial thickening.

Bottom Line: We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant.This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes.These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

View Article: PubMed Central - PubMed

Affiliation: Instituto Maranhense de Oncologia Aldenora Bello, São Luís, MA, Brasil.

ABSTRACT
The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. We observed a high frequency of CYP2D6 *10, with an allelic frequency of 0.14 (14.4%). The *3 allele was not present in the studied population, and *4 had an allelic frequency of 0.13 (13.8%). We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant. We also observed a high frequency of CYP2D6 *10, which had not been previously described in this specific population. This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes. These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

Show MeSH
Related in: MedlinePlus