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Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen.
This article was published in the following journal.
Name: Toxicology and applied pharmacology
In addition to the effect of CYP2D6 genetic polymorphisms, the metabolism of tamoxifen may be impacted by other factors with possible consequences on therapeutic outcome (efficacy, toxicity). This ana...
Development of a high performance liquid chromatography method with fluorescence detection for the routine quantification of tamoxifen, endoxifen, and 4-hydroxytamoxifen in plasma from breast cancer patients.
To date, several methods for quantification of tamoxifen and its metabolites have been developed, most of which employ liquid chromatography tandem-mass spectrometry (LC-MS/MS). These methods are high...
Tamoxifen is widely prescribed as adjuvant therapy in patients with early-stage breast cancer. It has been postulated that concentrations of endoxifen, the active metabolite of tamoxifen, are a better...
Cytochrome P450 2D6 (CYP2D6) is a major drug-metabolizing enzyme that exhibits large interindividual variability. Recent studies suggest that differential transcriptional regulation of CYP2D6 may be i...
Interleukin (IL)-8 is a proinflammatory cytokine, and high levels of IL-8 are associated with poor prognosis in many malignancies. The objective of this study was to explore the clinical benefit of mo...
In hormone-receptor positive breast cancer or DCIS (ductal carcinoma in situ) tamoxifen remains an important treatment option for patients before menopause and those patients after menopau...
Aim of work: 1. To estimate the frequency of Cyp2D6*1 and *4 alleles in Egyptian patients maintained on tamoxifen (20 mg/day) for management of ER +ve breast cancer. 2. To...
We hypothesized that subjects with CYP2D6*10 alleles may have a lower steady state levels of endoxifen due to reduced conversion of tamoxifen to endoxifen. Primary objectives: - ...
Tamoxifen is an important drug for the treatment of breast cancer. Used adjuvantly after operation in early breast cancer, tamoxifen reduces annual recurrence rate by half and cancer death...
This study is an observational study to determine phenotype and genotype of CYP2D6 as predictors of z-endoxifen concentrations in plasma of outgoing patients treated with tamoxifen for at ...
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2D6.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP2D6.
Any liquid used to replace blood plasma, usually a saline solution, often with serum albumins, dextrans or other preparations. These substances do not enhance the oxygen- carrying capacity of blood, but merely replace the volume. They are also used to treat dehydration.
A fluid-filled closed cavity or sac that is lined by an EPITHELIUM and found in the BREAST. It may appear as a single large cyst in one breast, multifocal, or bilateral in FIBROCYSTIC BREAST DISEASE.
A common and benign breast disease characterized by varying degree of fibrocystic changes in the breast tissue. There are three major patterns of morphological changes, including FIBROSIS, formation of CYSTS, and proliferation of glandular tissue (adenosis). The fibrocystic breast has a dense irregular, lumpy, bumpy consistency.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
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