Hopeful
01-22-2008, 07:30 AM
http://www.breastcancersource.com/breastcancersourcehcp/6096_31956_0_0_0.aspx?
Here is the salient info from the paper which was the basis for this article:
"The molecular mechanisms of tamoxifen resistance are still not fully understood, but recent literature suggests a common theme of tamoxifen-induced ER serine phosphorylation leading to the recruitment of nuclear hormone coactivators and increased expression of ER-regulated grwoth-promoting genes. There have been a number of molecules implicated in ER serine phosphorylation including protein kinase A, Her2/neu, and Pak1. In particular, these studies highlight the importance of ER phosphorylation at serine 118 and serine 305 that can lead to an ER agonistic response upon tamoxifen exposure. Interestingly, Her2/neu has also been shown to phosphorylate p21 via AKT, thereby excluding it from the nucleus and abating its growth-inhibitory properties. . . . this report demonstrates that loss of p21 can reverse the cellular response to this SERM from antagonistic to agonistic."
IMHO, this study demonstrates how Oncotype Dx scores can be compromised in the Her2+ population, and should not be used as the sole determinant for adjuvant tx for Her2+ patients. The test was validated retrospectively using a group of Her2+ women who received only Tamoxifen as adjuvant tx. The test assumes that the test subject is contemplating the same therapy as the validation group, and projects a result based on that assumption. If the basis of comparison is a group of patients taking only a drug that is likely to become a promoter of the disease in a substantial number of people, the scores are all going to come back very high.
Hopeful
Here is the salient info from the paper which was the basis for this article:
"The molecular mechanisms of tamoxifen resistance are still not fully understood, but recent literature suggests a common theme of tamoxifen-induced ER serine phosphorylation leading to the recruitment of nuclear hormone coactivators and increased expression of ER-regulated grwoth-promoting genes. There have been a number of molecules implicated in ER serine phosphorylation including protein kinase A, Her2/neu, and Pak1. In particular, these studies highlight the importance of ER phosphorylation at serine 118 and serine 305 that can lead to an ER agonistic response upon tamoxifen exposure. Interestingly, Her2/neu has also been shown to phosphorylate p21 via AKT, thereby excluding it from the nucleus and abating its growth-inhibitory properties. . . . this report demonstrates that loss of p21 can reverse the cellular response to this SERM from antagonistic to agonistic."
IMHO, this study demonstrates how Oncotype Dx scores can be compromised in the Her2+ population, and should not be used as the sole determinant for adjuvant tx for Her2+ patients. The test was validated retrospectively using a group of Her2+ women who received only Tamoxifen as adjuvant tx. The test assumes that the test subject is contemplating the same therapy as the validation group, and projects a result based on that assumption. If the basis of comparison is a group of patients taking only a drug that is likely to become a promoter of the disease in a substantial number of people, the scores are all going to come back very high.
Hopeful