Tamoxifen is an antiestrogen drug commonly used to treat breast cancer and has been shown to cause prolongation of the electrocardiographic QT interval in humans. Because QT prolongation could influence cardiac arrhythmias, we sought to determine the electrophysiologic mechanism(s) underlying the tamoxifen action. The whole-cell patch-clamp technique was used to study the effect of tamoxifen on...

The reasons why human mammary tumors become resistant to tamoxifen therapy are mainly unknown. Changes in gene expression may occur as cells acquire resistance to antiestrogens. We therefore undertook a comparative gene expression analysis of tamoxifen-sensitive and tamoxifen-resistant human breast cancer in vivo models using Affymetrix oligonucleotide arrays to analyze differential gene expres...

BACKGROUND The prognostic accuracy for distant recurrence-free survival using a 21-gene reverse-transcriptase polymerase chain reaction (RT-PCR) assay underwent validation in 668 lymph node-negative, estrogen receptor-positive women with early-stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program (NSABP) B-14. The predictive accuracy for treatment efficacy also un...

Several large, prospective trials have evaluated tamoxifen compared with placebo for breast cancer risk reduction in women at increased risk for breast cancer. Analysis of the large, prospective breast cancer risk-reduction trials that used tamoxifen estimated that tamoxifen decreased breast cancer incidence by 38% on average and estrogen receptor-positive tumors by 48%. Tamoxifen is known to h...

BACKGROUND Our study aimed to assess the endometrial cancer risk after tamoxifen adjuvant treatment for female breast cancer patients in Taiwan. MATERIALS AND METHODS A total of 74,280 breast cancer patients between January 1997 and December 2004 were included in the study; 39,411 received tamoxifen treatment and 34,869 did not. Tamoxifen-associated endometrial cancer was defined as endometri...

Macrophage adipocyte fatty acid-binding protein (FABP4) plays an important role in foam cell formation and development of atherosclerosis. Tamoxifen inhibits this disease process. In the present study, we determined whether the anti-atherogenic property of tamoxifen was related to its inhibition of macrophage FABP4 expression. We initially observed that tamoxifen inhibited macrophage/foam cell ...

Endocrine therapy plays an important role in the management of all stages of breast cancer, and the development of effective endocrine therapies has focused on modifying the response of hormone-sensitive tumors to estrogen. The most widely used agents are the nonsteroidal antiestrogens or selective estrogen receptor (ER) modulators, the class to which tamoxifen, the standard in terms of antiest...

The cytochrome P450 (P450)-mediated biotransformation of tamoxifen is important in determining both the clearance of the drug and its conversion to the active metabolite, trans-4-hydroxytamoxifen. Biotransformation by P450 forms expressed extrahepatically, such as in the breast and endometrium, may be particularly important in determining tissue-specific effects of tamoxifen. Moreover, tamoxife...

Wild-type erbB-2/neu transgenic mice were used to study the interactions between tamoxifen and dietary phytoestrogens (or isoflavones) by dose and form in vivo . Mice were randomized to one of four dietary formulas and implanted with an 8-week continuous-release tamoxifen or placebo pellet at 8 weeks of age. In placebo-treated mice, soy meal diet (but not diets supplemented with low-dose or hig...

Purpose Whether tamoxifen affects the risk of neurodegenerative disease is controversial. This nationwide population-based study investigated the risk of Parkinson's disease (PD) associated with tamoxifen treatment in female patients with breast cancer using Taiwan's National Health Insurance Research Database. Methods A total of 5,185 and 5,592 female patients with breast cancer who did and ...