neoadjuvant study shows AI treatment may upregulate her2
 

Br J Cancer. 2009 Sep 15. [Epub ahead of print]

Nuclear receptor co-activators and HER-2/neu are upregulated in breast cancer patients during neo-adjuvant treatment with aromatase inhibitors.

Flågeng MH, Haugan Moi LL, Dixon JM, Geisler J, Lien EA, Miller WR, Lønning PE, Mellgren G.
[1] Institute of Medicine, University of Bergen, N-5021 Bergen, Norway [2] The Hormone Laboratory, Haukeland University Hospital, N-5021 Bergen, Norway.
Background:Acquired resistance to endocrine therapy in breast cancer is poorly understood. Characterisation of the molecular response to aromatase inhibitors in breast cancer tissue may provide important information regarding development of oestrogen hypersensitivity.Methods:We examined the expression levels of nuclear receptor co-regulators, the orphan nuclear receptor liver receptor homologue-1 and HER-2/neu growth factor receptor using real-time RT-PCR before and after 13-16 weeks of primary medical treatment with the aromatase inhibitors anastrozole or letrozole.Results:mRNA expression of the steroid receptor co-activator 1 (SRC-1) and peroxisome-proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) was correlated (P=0.002), and both co-activators increased during treatment in the patient group as a whole (P=0.008 and P=0.032, respectively), as well as in the subgroup of patients achieving an objective treatment response (P=0.002 and P=0.006). Although we recorded no significant change in SRC-3/amplified in breast cancer 1 level, the expression correlated positively to the change of SRC-1 (P=0.002). Notably, we recorded an increase in HER-2/neu levels during therapy in the total patient group (18 out of 26; P=0.016), but in particular among responders (15 out of 21; P=0.008).Conclusion:Our results show an upregulation of co-activator mRNA and HER-2/neu during treatment with aromatase inhibitors. These mechanisms may represent an early adaption of the breast cancer cells to oestrogen deprivation in vivo.British Journal of Cancer advance online publication, 15 September 2009; doi:10.1038/sj.bjc.6605324 www.bjcancer.com.
PMID: 19755984

since rate increased among responders, question is if they recurred.

Will check article further

Re: neoadjuvant study shows AI treatment may upregulate her2
 

Tamoxifen has been shown to upregulate Her2 also: http://cancerres.aacrjournals.org/cg...tract/68/3/826

Both studies support the logic for simultaneously blocking both the ER and Her2 pathways.

Hopeful

Re: neoadjuvant study shows AI treatment may upregulate her2
 

The most pertinent question for triple pos. is: should we take A.I.'s without Herceptin? We are to do 4 years without anything blocking the Her-2 while on an estrogen blocker.

Re: neoadjuvant study shows AI treatment may upregulate her2
 

update --looked at the original article

many pts were her 2 undetermined, some were her2-, one was her2+

why don't they just go back to the specimens and her2 test??? oh, well

Re: neoadjuvant study shows AI treatment may upregulate her2
 

Or, maybe the point is that antihormonals can upregulate Her2 even if the original tumor was not Her2+

Re: neoadjuvant study shows AI treatment may upregulate her2
 

Becky,

That is definitely the message in the link I posted on tamoxifen resistance. The researchers conclude by suggesting anti-her2 therapy for anyone on a tamoxifen trial in the future.

Hopeful

Re: neoadjuvant study shows AI treatment may upregulate her2
 

Could you please explain what the term "upregulate Her2" means?

Thanks!

Re: neoadjuvant study shows AI treatment may upregulate her2
 

Bumping this up for Alice.

Chelee

Re: neoadjuvant study shows AI treatment may upregulate her2
 

cancer cell growth/survival/effects have been found to be due to various pathways being either upregulated (encouraged, turned up in volume) or supressed. There are various feedback loops involved so turning one pathway up may turn another up as well, and yet another down. In other words, things are interrelated.

Cancer can escape blocking one pathway or route by substituting another route to allow it to grow, spread, etc.

In this study starving the her2+er+ tumor (and in some patients the her2-ER+ tumors) of estrogen by using an AI, just caused the cancer cell to increase its usage (upregulate ) of the alternate pathway, in this case the her2 pathway in order to continue to grow, thrive and spread.

This article brings into question whether alternative and/or additional drugs should be given to prevent this escape before it happens ie, faslodex instead of AIs (which may or may not work) or a HSP90 inhibitor which affects both her2 and ER from what I understand.

Hope this helps

Re: neoadjuvant study shows AI treatment may upregulate her2
 

Lani,

Do you suggest faslodex because it has a different interaction; or has it been shown or theorized that it does not upregulate Her2?

Thanks

Terri

Re: neoadjuvant study shows AI treatment may upregulate her2
 

since there seems to be cross talk between the ER and the her 2 receptor using a drug which irreversibly degrades the ER might possibly be more effective than just starving the ER of its ligand (estrogen)

Having no ER to cross talk with the her2 receptor may be more effective at stopping growth than having a "starved" ER talk to the her2 receptor, upregulate its pathway and give the tumor an alternative pathway to escape the ligand starvation of the ER.

Re: neoadjuvant study shows AI treatment may upregulate her2
 

Hmm. I'm going to have to decide whether or not to continue on an AI, after 5 years of arimidex. I was Her2 ++ initially. On the other hand, I'm almost 6 years out from diagnosis and doing well. So it probably didn't harm me too much. Oh well, questions, questions.

Jacqueline