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Old 05-23-2014, 11:27 AM   #1
'lizbeth
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Post Synergistic Interactions between Tamoxifen and Trastuzumab (Herceptin)

Synergistic Interactions between Tamoxifen and Trastuzumab (Herceptin)

  1. Athanassios Argiris,
  2. Chun-Xia Wang,
  3. Steve G. Whalen, and
  4. Michael P. DiGiovanna
+ Author Affiliations
  1. Yale University School of Medicine, Departments of Internal Medicine (Section of Medical Oncology) and Pharmacology, and the Yale Cancer Center, New Haven, Connecticut

Abstract

Purpose: HER-2/neu and estrogen receptor (ER) are critical in the biology of breast carcinoma, and both are validated therapeutic targets. Extensive interactions between the signaling pathways of these receptors have been demonstrated. This suggests that targeting both receptors simultaneously may have a dramatic effect on the biology of breast cancer. This hypothesis was tested in cell culture experiments.
Experimental Design: ER-positive, HER-2/neu-overexpressing BT-474 human breast carcinoma cells were cultured in the presence of the anti-HER-2/neu therapeutic antibody trastuzumab (Herceptin), the antiestrogen tamoxifen, or both. The effects on cell growth, cell cycle distribution, clonogenicity, survival, and the level and activity of HER-2/neu were examined.
Results: The combination of tamoxifen and Herceptin resulted in synergistic growth inhibition and enhancement of cell accumulation in the G0-G1 phase of the cell cycle, with a decrease in cells in S phase. Clonogenicity was inhibited in the presence of each drug and more so by the combination, although prior exposure to drugs did not affect subsequent clonogenicity in drug-free media, and neither drug nor the combination induced apoptosis. Herceptin, but not tamoxifen, inhibited signaling by HER-2/neu.
Conclusions: The combination of tamoxifen and Herceptin is formally demonstrated to result in synergistic growth inhibition and enhancement of G0-G1 cell cycle accumulation. In vitro, the individual drugs or combination produces a cytostatic effect. These results suggest that combined inhibition of ER and HER-2/neu signaling may represent a powerful approach to the treatment of breast cancer.





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http://clincancerres.aacrjournals.or...10/4/1409.full
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Old 05-23-2014, 11:29 AM   #2
'lizbeth
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Re: Synergistic Interactions between Tamoxifen and Trastuzumab (Herceptin)

This study is 10 years old and posted to help examine the question of benefits / interference of combining Tamoxifen with Herceptin.
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