Tamoxifen administered in the diet (420 ppm) to Wistar rats (TOX:P) for only 3 months caused cumulative hepatic DNA damage as assessed by 32P-postlabeling, consistent with the proposal that tamoxifen is a genotoxic carcinogen in this species. Promotion of tumor development with phenobarbital after discontinuation of dietary tamoxifen resulted in the formation of liver carcinomas after 9 months....

PURPOSE To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. To elucidate both strategies comprehensively we used a physiologically-based pharm...

Gene expression profiling aimed at classifying and prognosing breast cancer has yielded signatures with little, if any, concordance. However, expression arrays used in these studies do not discriminate alternate RNA splice isoforms that vary widely in cancer and may resolve this problem. In this study, we profiled splice isoforms in a panel of tamoxifen-sensitive and -resistant cell lines, defi...

Gene expression profiling aimed at classifying and prognosing breast cancer has yielded signatures with little, if any, concordance. However, expression arrays used in these studies do not discriminate alternate RNA splice isoforms that vary widely in cancer and may resolve this problem. In this study, we profiled splice isoforms in a panel of tamoxifen-sensitive and -resistant cell lines, defi...

The PI3K/Akt/mTOR is a key signaling system that binds oncogenes and various receptors to many cell functions, promotes estrogen resistance, the most frequently activated pathway in malignant neoplasm, including breast cancer (BC). About 70 % of BC hormone‑receptor positive endocrine therapy main component treatment for patients. Tamoxifen remains one basic drugs adjuvant estrogen‑positive Howe...

AIMS Tamoxifen is a selective oestrogen receptor modulator widely used in the prevention and treatment of breast cancer. Women receiving long-term tamoxifen therapy do not experience cardiac arrhythmias although acute perfusion of tamoxifen has been shown to inhibit cardiac K(+) currents. This observation suggests that chronic tamoxifen treatment does not negatively modulate cardiac K(+) curren...

Tamoxifen is the accepted therapy for patients with estrogen receptor-α (ERα)-positive breast cancer. However, clinical resistance to tamoxifen, as demonstrated by recurrence or progression on therapy, is frequent and precedes death from metastases. To improve breast cancer treatment it is vital to understand the mechanisms that result in tamoxifen resistance. This study shows that concentratio...

BACKGROUND In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy. METHODS Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classifica...

The nonsteroidal antiestrogen tamoxifen is widely used in breast cancer treatment and is currently under evaluation as a chemopreventive agent for individuals at high risk of contracting the disease. The effects of tamoxifen administration on the expression of xenobiotic metabolizing enzymes in F344 rat liver have been investigated. Tamoxifen administration for 7 days produced a dose-dependent ...