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Article
Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors
Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a...
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Article
Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer
Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma conce...
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Article
Open AccessThe IGNITE network: a model for genomic medicine implementation and research
Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information (as reflected by genoty**, sequencing, family history or other data) to inform clinical decision-...
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Article
Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover
Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease ...
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Article
Factor XIII Val34Leu polymorphism and recurrent myocardial infarction in patients with coronary artery disease
Factor XIII (FXIII) is necessary for cross linking of fibrin strands and generation of stable fibrin clot. FXIII Val34Leu is a common genetic single nucleotide polymorphism that has been associated with accele...
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Article
Genetic associations with toxicity-related discontinuation of aromatase inhibitor therapy for breast cancer
Up to 25 % of patients discontinue adjuvant aromatase inhibitor (AI) therapy due to intolerable symptoms. Predictors of which patients will be unable to tolerate these medications have not been defined. We hyp...
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Article
Pharmacogenetics and healthcare outcomes in patients with chronic heart failure
To test for associations between genetic polymorphisms of adrenergic receptors (AR) and other candidate genes and healthcare utilization in heart failure patients, taking into account other important factors, ...
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Article
The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents
To improve the treatment of breast cancer, there has been a need for alternative aromatase inhibitors (AIs) that bring about adequate aromatase inhibition, while limiting side effects. Since two tamoxifen meta...
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Article
Functional Characterization of a Genetic Polymorphism in the Promoter of the ESR2 Gene
The ESR2 gene encodes the estrogen receptor beta protein. Several studies have shown that genetic variants in the ESR2 gene are associated with a variety of clinical phenotypes. However, very little is known abou...
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Article
Comparison of breast cancer recurrence risk and cardiovascular disease incidence risk among postmenopausal women with breast cancer
The majority of breast cancers are diagnosed in postmenopausal women. Competing comorbidities, particularly cardiovascular disease (CVD), should be considered when individualizing adjuvant therapies for these ...
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Article
Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer
The mechanism of tamoxifen action in the treatment of breast cancer is believed to be via active metabolites that act as potent estrogen receptor antagonists. Attempts to identify relationships between active ...
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Article
Open AccessMethadone adverse reaction presenting with large increase in plasma methadone binding: a case series
The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics...
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Article
Open AccessA modulated empirical Bayes model for identifying topological and temporal estrogen receptor α regulatory networks in breast cancer
Estrogens regulate diverse physiological processes in various tissues through genomic and non-genomic mechanisms that result in activation or repression of gene expression. Transcription regulation upon estrog...
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Article
Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort
Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes i...
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Article
Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4′-methanol-bisbenzonitrile in vitro
To determine the inhibitory potency of letrozole and its main human metabolite, 4,4′-methanol-bisbenzonitrile, on the activities of eight cytochrome P450 (CYP) enzymes.
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Article
Exploratory study evaluating the association of polymorphisms of angiogenesis genes with hot flashes
Purpose Hot flashes are a common symptom and an important cause of decreased quality of life in women with breast cancer. Hot flashes involve vasodilatation and flushing, however, their complex etiology is not fu...
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Article
Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy
Thromboembolism is a serious complication of tamoxifen therapy in women with breast cancer. Banked DNA from tamoxifen-treated individuals with breast cancer from the Marshfield Clinic Personalized Medicine Res...
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Article
Association of polymorphisms of angiogenesis genes with breast cancer
Few studies have systematically explored a pathway approach: to test the association of multiple polymorphisms from multiple genes important to angiogenesis simultaneously with risk of breast cancer. We repor...
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Article
Creating and evaluating genetic tests predictive of drug response
Recent advances in genomic knowledge and associated technologies should help accelerate the development of genetic tests that can predict drug response and toxicity; however several challenges remain. Here, We...
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Article
The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen
Tamoxifen is biotransformed to the potent anti-estrogen, endoxifen, by the cytochrome P450 (CYP) 2D6 enzyme. CYP2D6 genetic variation and inhibitors of the enzyme markedly reduce endoxifen plasma concentrations i...
