just wondering

[lolam]

When my kids were little I was leary of them getting antibiotics for every illness as I wanted their bodies to heal themselves and not be dependent on them. I thought that that would deter their immune systems from fighting.

So now I wonder about herceptin. Isn't it like an antibiotic? Does my immune system now think that herceptin will do what it now doesn't have to do?

It seems also that an antibiotic would eventually lose its effectiveness. Could the cancer eventually outsmart it if it had enough time to figure out how to?

I am wondering if the ones who were on herceptin during the first trial and still on it have no cancer in their bodies for some reason, and it is not the heceptin that is keeping them clear of tumors. Am I on herceptin because once I had recurrence there is absolutely no way at all that I do not have cancer cells in my blood? Or are we guessing that more than likely I have cancer cells in my body? My doctor says, "Now Lola you know there is no cure for you since recurrance." So my immune system can no longer handle this disease.

I do not have cancer because I have a deficiency of Herceptin! I have cancer because my immune system failed to kill the cancer cells this time right? Is herceptin like my insurance company, in that as long as they are paying my bill, I don't complain about the outrageous prices they charge? As long as I have herceptin, my immune system doesn't pay so why try to enhance it?

Just wondering!

Hugs, Lola

[Paul]

Lola,

Wow! I had to take on the challenge of addressing this one. The problem with cancer generally is that most of the time, our immune system will not attack it because it can not "see" it. This, in a nutshell, is what makes cancer such a tempest in a teapot. Cancer is, in essence, part and parcel of us. It is not a foreign bacteria or virus, it is our own cells that have lost the ability to self-regulate. The immune system does not see it as a threat.

Now, one of the functions of herceptin is to lock on to the HER-2 receptor on the outside of the cancer cell. When the herceptin antigen locks into the receptor, it has several effects. First, the cancer cell is now "visible" to the immune system because the antigen alerts the immune system that something is out of the norm. Second, the HER-2 receptor blockage helps prevent that receptor from binding with HER-1 and HER-3 on the outside of the cell. The loss of binding ability for HER-2 can cause loss of cell proliferation. Third, herceptin "backs up" chemo by making it more difficult for the cancer cell to repair the damage to its DNA caused by Chemo.

So, if anything, herceptin allows the immune system to "see" a problem cell that it otherwise would not see. As far as I know, it does not weaken the immune system, it simply gives the immune system better "vision" if you will.

Now, your point regarding the ability of cancer cells to mutate is fair. In fact, the way I understand it is that cancer is effectively a genetic defect of sorts. Each time a defective cancer cell replicates, it has the ability to change. Keep in mind that cancer cells are human cells and normal human cells are remarkably resilient with an incredible ability to adapt. Cancer cells are no different.

Herceptin works by blocking the HER-2 receptor on the outside of the cell. If herceptin fails to prevent HER-2 from pairing with HER-1 and HER-3, the proliferation process may continue by so-called "kinase" activity within the cell. Drugs like GSK 572016, block the HER-1 and HER-2 kinase activity within a cell. Omnitarg prevents HER-2 from binding with HER-1, HER-3 and HER-4. As we learn more about cellular biological proliferation pathways, the drug companies figure out ways to "block" the proliferation path of the cancer cell in targeted fashion. Because all pathways used by the human cell to proliferate are not known, research continues to figure it out for the majority of patients.

Keep in mind, that when you shut down cellular pathways to battle cancer, you must ensure that you do not harm normal body functions. This is why Herceptin has cardiotoxicity as a side effect in about 5% of the cases. As it turns out, HER-2 genes are important to cardiac function. This fact was not known when herceptin was discovered.

As for Stage IV Lola, you will not hear a doctor use the "cure" word. The term "no evidence of disease" was created for this purpose. Long-term studies suggest that cancer, as a technical matter, can recur in Stage IV at any time. But, the stats also suggest that after the passage of a certain amount of time without recurrence, the likelihood of recurrence decreases for the majority of patients. Some recent studies suggest that metastatic cancer is caused by just a few "master" cells. If initial treatment does not kill these master cells, they continue to proliferate. The real answer is that cancer is a complicated problem and we do not have all the answers yet.

With all this said, keep in mind that herceptin is effective for 40 to 50% of women (the stats may increase once FISH testing to determine HER-2 status becomes the norm). If herceptin, or GSK 572016 or APC 8024, can control HER-2 positive cancer in Stage IV, who cares what terminology is used as long as the cancer stays in check.

Keep in mind that Barbara Bradfield used Herceptin and cisplatin one time in one clinical trial in the early 1990s and she has been NED ever since. Ginger Empey has used herceptin consistently since that same time period, and she is also NED. As you can see, we have much to learn about the human cell and why some people have recurrence and some don't. Despite that fact, I believe that in fifty years, Dennis Slamon, M.D. (credited with the discovery of Herceptin) will be considered the Louis Pasteur or Jonas Salk of my generation. The idea to attack genetic defects in cancer with targeted therapies is truly novel and strikes me as the right approach.

[Merridith]

Hi Lola:

I recall reading that there is some minor concern with loss of immunity with herceptin therapy. I tried to find the research article again but couldn't.

The concerns with immunity loss were minor because the stats only very slightly supported the concern. No direct test had actually confirmed anything.

I did find this link that discusses herceptin immunity in general terms: http://www.breastcancer.org/tre_opts_holbo...tml

Hope (http://www.breastcancer.org/tre_opts_holbodsys.html

Hope) this helps,
Regards,
Merridith

[Kathy]

Paul
Thank you ever so much for taking the time to present these great explanantions!