Does Herceptin Reverse The Estrogen Receptor?????
 

A lot of research seems to indicate that herceptin can reverse the estrogen receptor in her2+ er-, pr- bc. Has anybody else heard this?

Robin

I have the downloaded an abstract of an article by Munzone et al in Breast Cancer Research 2006, 8:R4 'Reverting estrogen-receptor-negative phenotype in Her-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy'. It hasn't got a link at the bottom so I can't paste it in. I expect I found it via pub med. This is a very small sample of 10 patients with advanced BC, Her2+ve, ER and PR -ve, who received Herceptin weekly as a monotherapy or combined therapy. 3 of the 10 showed overexpression of er first appearing after 9,12 and 37 weeks.

We are using this to ask for a re-test for my sis who has progressed on herceptin, in case hormonal therapies may become an option for her.

Hope this helps

Sue M

Please see my post from 12/14/05...
 

So...
 

Then being hormone-receptor positive, a better situation, could with the use of Herceptin leave one hormone-receptor negative, a less advantageous situation?

A.A.

Your status should should not change if you are ER+PR+ (or neg for PR) if you are also taking a hormonal at the same time as Herceptin (and blocking both receptors simultaneously).


I have read that one can change from negative to positive, both in regard to Her 2 status or hormonal status. I think the change may be "provoked" if you are on the edge to begin with (ie: tested as Her 2 +2 or +1) or so slightly hormone positive that you are considered negative (for example, I am less than 5% PR positive and I am told that it is considered negative (but I am 50% ER positive)).

Becky

Hi AA, I think the rationale for the hormonal receptor reversing is so the cancer cells can survive via of the estrogen pathway once the her2 pathway is shut down. It just doesn't seem like a cancer cells would want to shut off an alternate good growth pathway by becoming estrogen negative. Ney, they would want to keep the estrogen pathway upregulated or positive so they could grow so I don't see how Herceptin would increase the chances of evolving from a estrogen positive to negative state.

It would be interesting to know why cancers become estrogen negative. I've read that once cancer cells are really growing fast, the estrogen receptor gets downregulated and pathways like her2 take over to drive the cancer. Seemingly, new research seems to indicate all this can be reversed with Herceptin, interesting.

Forgot to log in.

Robin

I see Robin's point why ER would down-regulate under unimpeded proliferation but....if you are taking herceptin, most research indicates up-regulation of ER through the survival instinct of x-talk. Lapatinib for example, has re-sensitizing effects on ER+ tamoxifen resistance BC cells. This is because the cancer has a multi-pathway fail-safe survival system. The goal of targetted therapies is to shutdown enough pathways to cause tumor death, as opposed to cellular death alone.

If I were the king of the cancer fighters, in HER2 cancers I would block HER1, HER2, and hopefully HER3 (either with pertuzumab or a combo of lapatinib and herceptin), P13K (which we try with curcumin, but there are better drugs under development), cox2 inhibitor (celebrex), ER (Faslodex seems to have the best results), VEGF (with avastin and maybe even add in some lucentis which is used in adult macular degeneration), c-myn and P53 inhibitors and probably a cyto-toxic drug such as xeloda (which is really a pro-drug there it isn't systemic) along with neupogen support (neupogen has been shown to mobilize anti-cancer t-cells).

OK, I just left the cat out of the bag because that is what I am going to push for a treatment regime for Linda. She has an appointment in Seattle on Jan 25 with one of their specialists. I'm sure she won't get the whole bag and alot has to do with $$$ BUT, I am going to ask for each of these pathways to be addressed with either a logical "can't do that " explanation of or tx. I know that we can't cover all the bases in one regime but......

Thanks for starting this thread,
A