HER2 Support Group Forums - View Single Post - Another Study on Her2 and Tamox Resistance

Hopeful · 06-27-2008, 07:18 AM

Terri,

The above presentation was from the same conference, but not exactly the one I was looking for. Here is one much more germaine to your question, also by Ken Osborne: http://www.cancerconf.com/media/2008.../WEB/index.htm

The title is "Insights on Resistance to Hormonal Therapy"

Here is the abstract:

There are many potential mechanisms for de novo and acquired resistance to endocrine therapy. Absence of estrogen receptor (ER) in the tumor or loss of ER expression over time results in endocrine therapy resistance, although ER loss occurs in only about 20% of the patients treated with Tamoxifen. Loss of progesterone receptor expression, on the other hand, is common, and might be related to increased signaling from growth factor receptor pathways. Clinical and preclinical studies suggest that overactive growth factor receptor signaling, either due to de novo amplification of Her2 or to increasing levels of epidermal growth factor receptor and Her2 during endocrine therapy, is a potential reistance mechanism. Therapies targeting ER can be enhanced by simultaneous treatment with growth factor receptor inhibitors. In clinical breast cancer, Her2 amplification is known in some patients to confer resistance to Tamoxifen and estrogen deprivation therapies. In the recent TAnDEM trial, in patients with Her2+ positive tumors, the addition of trastuzumab to an aromatase inhibitor resulted in more frequent responses and longer time to progression (TTP) compated to an aromatase inhibitor alone. In a more recent trial in ER+ patients unselected by Her2 expression, gefitinib/tamoxifen yielded modestly superior clinical benefit rates and TTP compared to Tamoxifen alone. Clinical trials also suggest that 12%-35% of tumors will change from Her2- to Her2+ during endocrine therapy. Thus, there are preclinical and clinical data to support the idea that some patients might need a combination of ER and Her targeted therapy for optimal treatment. The key will be to identify this small group of subpatients a priori. (emphasis mine).

I am not a medical professional, and this is MHO, but if tamoxifen can upregulate some Her2- patients to the point they are Her2+, I really think all Her2+ patients should be very cautious about taking Tamoxifen without a corresponding Her2 downregulator.

Hopeful

06-27-2008, 07:18 AM	#8
Hopeful Senior Member Join Date: Aug 2006 Posts: 3,380	Terri, The above presentation was from the same conference, but not exactly the one I was looking for. Here is one much more germaine to your question, also by Ken Osborne: http://www.cancerconf.com/media/2008.../WEB/index.htm The title is "Insights on Resistance to Hormonal Therapy" Here is the abstract: There are many potential mechanisms for de novo and acquired resistance to endocrine therapy. Absence of estrogen receptor (ER) in the tumor or loss of ER expression over time results in endocrine therapy resistance, although ER loss occurs in only about 20% of the patients treated with Tamoxifen. Loss of progesterone receptor expression, on the other hand, is common, and might be related to increased signaling from growth factor receptor pathways. Clinical and preclinical studies suggest that overactive growth factor receptor signaling, either due to de novo amplification of Her2 or to increasing levels of epidermal growth factor receptor and Her2 during endocrine therapy, is a potential reistance mechanism. Therapies targeting ER can be enhanced by simultaneous treatment with growth factor receptor inhibitors. In clinical breast cancer, Her2 amplification is known in some patients to confer resistance to Tamoxifen and estrogen deprivation therapies. In the recent TAnDEM trial, in patients with Her2+ positive tumors, the addition of trastuzumab to an aromatase inhibitor resulted in more frequent responses and longer time to progression (TTP) compated to an aromatase inhibitor alone. In a more recent trial in ER+ patients unselected by Her2 expression, gefitinib/tamoxifen yielded modestly superior clinical benefit rates and TTP compared to Tamoxifen alone. Clinical trials also suggest that 12%-35% of tumors will change from Her2- to Her2+ during endocrine therapy. Thus, there are preclinical and clinical data to support the idea that some patients might need a combination of ER and Her targeted therapy for optimal treatment. The key will be to identify this small group of subpatients a priori. (emphasis mine). I am not a medical professional, and this is MHO, but if tamoxifen can upregulate some Her2- patients to the point they are Her2+, I really think all Her2+ patients should be very cautious about taking Tamoxifen without a corresponding Her2 downregulator. Hopeful