Pharmacogenomics of tamoxifen and aromatase inhibitors

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Pharmacogenomics of tamoxifen therapy.

BACKGROUND Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor-positive breast cancer. CONTENT Tamoxifen requires enzymatic activation by cytochrome P450 (CYP) enzymes for the formation of active metabolites 4-hydroxytamoxifen and endoxifen. As compared with the parent drug, both metabolites have an approximately 100-fold greater affinity for...

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Tamoxifen versus aromatase inhibitors for breast cancer prevention.

Long-term exposure to estradiol is associated with an increased risk of breast cancer, but the mechanisms responsible are not firmly established. The prevailing theory postulates that estrogens increase the rate of cell proliferation by stimulating estrogen receptor (ER)-mediated transcription, thereby increasing the number of errors occurring during DNA replication. An alternative theory sugge...

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Pharmacogenomics Guided-Personalization of Warfarin and Tamoxifen

The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date on the association between cytochrome P450 enzymes and the clinical end points of warfarin and tamoxi...

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Effectiveness of aromatase inhibitors and tamoxifen in reducing subsequent breast cancer

Tamoxifen (TAM) has been prescribed for decades and aromatase inhibitors (AIs) have been used since the early 2000s in preventing subsequent breast cancer. However, outside of clinical trials, the effectiveness of AIs is not established. We examined the long-term risk of subsequent breast cancer among survivors treated with TAM and AIs in a large health plan. The study included 22,850 survivors...

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The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients.

The traditional hormonal cascade of the 1970s and 1980s used tamoxifen followed by megestrol acetate and subsequently by aminoglutethimide. In the 1990s, however, three trials of third-generation aromatase inhibitors (AIs) compared with megestrol acetate and two trials of third-generation AIs compared with aminoglutethimide showed improved efficacy and decreased toxicity for the newer AIs. Thus...

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ژورنال

عنوان ژورنال: Cancer

سال: 2008

ISSN: 0008-543X,1097-0142

DOI: 10.1002/cncr.23192