Why does Herceptin stop working?

[julierene]

1) Haven't the studies shown that MORE Herceptin gives the same results as the current dosages without increasing effectiveness?

2) Can we make the theory that the tumor cells have capabilities of "learning"? I used the term loosely though, because I don't think cancer cells are necessarily smart - but maybe just survive out of 'natural selection'.


Cancer isn't just one type of cell replicating itself over and over. It's a product of an immune system that fails to recognize a damaged cell. My left breast had er-/pr- grade 3, IDC. My right breast had er+/pr- moderately differentiated DCIS. When I found out about that, I was like how? How could I be er-/pr- in one breast and er+/pr- in the other? It wasn't about the cancer... It was about my immune systems inability to recognize bad cells. Our normal cells are constantly learning how to overcome viruses and all sorts of stuff. The immune system seems smart when it comes to foreign attack (in a lot of cases). But when it comes to our own body malfunction, it struggles - especially when our genetics aren't perfect.

We already know that cells have a LOT of receptors on their surface. HER2/neu is just one of them. But for those of us who are HER2+++, that's great right? Here is a made up example:

I would think Herceptin Ineffectiveness is a mechanism where those tumor cells (in their active state) whose cell surface makeup has a few more IGF-IR receptors, survive and replicate after Herceptin has blocked all of the HER2 receptors on its surface. Even though the HER2 receptors are plugged, the immune system doesn't necessarily kill the cell. For many of us, the chemotherapy is what goes in and kills all the fast dividing cells. Just because the receptors are blocked, doesn't mean the cell is dead.

Those cells that have almost all HER2 receptors are killed (while in their active state), because chemo comes in and recognizes it as a fast dividing cell. While on Herceptin alone, the stuff that's maybe got some IGF-IR receptors - could live (if not in their active state, maybe while in their inactive state. I am on the side of the fence of oncology theory that believe cancer cells 'hide' while in their stem cell slowly dividing state - which is why they evade chemotherapy). As those cells live, I think more are replicated with 'possibly' more of those type of IGF-IR receptors. As all the HER2 receptors start to disappear (because those cancer cells were killed - either because they had no receptors left or the chemo killed them) - we get cancer cells that continue to divide - even while taking Herceptin. Then is it possible that HER2+++ status may change? Could you now be NER2- after years of being on Herceptin? Are other receptors, like EGF-IR, taking their place? <Or maybe the HER2/neu receptors are being blocked, but the IGF-IR unblocked receptors allow the cell to survive and divide?>

Is it plausible?

<I used IGF-IR just because it's a hot topic and I can't remember all the other ones abbreviations>
I am REALLY interested in this topic, sorry for the double post. I hope to hear some discussion on it. Thanks in advance for any brainstorming contributions. Julie

Hi
I know it is several months since you wrote this article but just want to tell you briefly my history. Diagnosed in march 2005 whilst pregnant, stage four - massive liver secondaries. Tumor was then - er+, her2 +++ and pr-. Had AC, then taxotere and herceptin. After 7 months of herceptin discovered I had lowered LVEF to 39%. Stopped herceptin, started heart medication. Two weeks ago I had my breast lump removed at my request and analysis showed - highly Er + BUT HER2 NEG. I have not had herceptin for 6 months. Have you found out much more about this since you wrote the article?

Look forward to any responses.

Rosheen

[Becky]

Julie


I agree with you 100%. I do not believe that Herceptin stops working, I believe the cancer changes in order to survive and reproduce (Darwinism at its finest).

I hope you and your family are doing well as you have not posted in awhile.

Kind regards

Becky

[julierene]

What sample did they use to test your HER2 status the first time?

[RobinP]

Hi Julie,

After reading your post, I do hope you are well and not progressing while on Herceptin. I think that it is possible for her2 status to change; however, this apparently happens less often than not according to an abstract I read from the 2005 SABC. Further, the change of her2 status they cited was from the primary to the metastatic and not necessarily a result due to taking Herceptin. Take care.

[julierene]

I am doing well. I am still NED, but Dec 05 was when I was dx Stage 4... so I still have a ways to go.

Thanks for the post! Julie