Association of CYP2D6 metabolizer status with mammographic density change in response to tamoxifen treatment
Li, J Czene, K Brauch, H Schroth, W Saladores, P Li, Y Humphreys, K Hall, P
Czene, K
Brauch, H
Schroth, W
Saladores, P
Li, Y
Humphreys, K
Hall, P
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Alternative Title
Abstract
Introduction: Not all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition. As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate the association between germline CYP2D6 polymorphisms and PMD change.Methods: Baseline and follow-up mammograms were retrieved for 278 tamoxifen-treated subjects with CYP2D6 metabolizer status (extensive (EM), heterozygous extensive/intermediate (hetEM/IM) or poor metabolizer (PM)). Logistic regression analyses were conducted comparing subjects who experienced >10% reduction in PMD to those who experienced ?10% reduction or increase.Results: After multivariate adjustment, PMD change was found to be significantly associated with the degree of CYP2D6 enzyme functionality (Ptrend = 0.021). Compared with EM, hetEM/IM and PM were 72% (95% confidence interval (CI): 0.10 to 0.79) and 71% (0.03 to 2.62) less likely to experience a >10% reduction, respectively.Conclusions: Tamoxifen-induced change in PMD appears to have a genetic component. © 2013 Li et al.; licensee BioMed Central Ltd.
Keywords
cytochrome P450 2D6, tamoxifen, antineoplastic hormone agonists and antagonists, tamoxifen, adult, aged, article, body mass, breast cancer, enzyme polymorphism, female, follow up, genetic variability, human, major clinical study, mammographic density, mammography, quantitative trait, treatment response, breast tumor, congenital malformation, genetic polymorphism, genetics, genotype, mammary gland, mammographic density, metabolism, middle aged, pathology, prognosis, risk factor, treatment outcome, Aged, Antineoplastic Agents, Hormonal, Breast Neoplasms, Cytochrome P-450 CYP2D6, Female, Genotype, Humans, Mammary Glands, Human, Middle Aged, Polymorphism, Genetic, Prognosis, Risk Factors, Tamoxifen, Treatment Outcome
Source Title
Breast Cancer Research
Publisher
Series/Report No.
Collections
Rights
Attribution 4.0 International
Date
2013
DOI
10.1186/bcr3495
Type
Article