Paul or anyone, her2+ without herceptin

My wife is stage 2b, with 4 positive nodes, er/pr-. Have any of y'all hear of long term survivors without recurrence? She didn't get into the herceptin arm.

Hi there,
I am a 2 1/2 year survivor without it, because of the same situation. I would reccomend that you try to find an onocoligist that will give it to you anyway. Mine has finally agreed to after alot of discussion and persistance!!

Hi Eugene,
I agree with Carlye, it would be wise to look for a doctor who is open to the idea of Herceptin off-protocol. Since your wife is Her2+, ER/PR- with positive nodes, her chance of recurrence is higher.
I was Stage 3b, Her2+, ER/PR- with 5 of 5 positive nodes, so my situation was more grave than your wife's, but in hindsight would have pushed for Herceptin off-protocol had I known then what I know now.
Best Wishes, Lolly

Thanks for y'all suggestions on getting herceptin, but its been 2 years since her dx. At the time MD Anderson would not give her herceptin off protocol. I'm concern about recurrence since she was her2+ and node positive. I'm just wondering if there are long term survivors who are her2+ and node positive. Thanks.

Eugene,
I am a long term survivor--20 years! I had 12 or 24 nodes involved. Chemo for one year--before Herceptin was tested. I am Her2+++-- am now taking Herceptin with Arimidex and stable after 15 months.

Dear Eugene,

In the 1800s, Benjamin Disraeli, a famous Prime Minister of England, said, "There are three kind of lies: lies, damn lies, and statistics." I'm not a big fan of statistics because, to the extent that they make you over-confident/complacent or extremely pessimistic, they seriously impact the motiviation of a women to properly fight this disease. For example, there are stats around that suggest that less than 50% of HER-2 positive women respond to Herceptin. It should be noted that all statistics take a "hindsight" approach and look "backwards." The fact is, when these stats were compiled, HER-2 status was determined primarily by IHC testing. Some believe that if FISH testing had been around since the advent of Herceptin, the monotherapy response rate would be in excess of fifty percent and the chemo/Herceptin response rate would be in the 60 percentile. In addition, the science is moving at breakneck speed and most data published is potentially questionable within 24 months of publication.

There are some 1998 HER-2 statistics provided at www.her2status.com. You need to register to view the information on the site. It is sponsored by Hoffman-LaRoche, the company that promotes and sells Herceptin outside the U.S. The graphs seem to indicate that the biggest risk of recurrence for a strongly HER-2 positive patient occurs prior to or around 36 months to 48 months after diagnosis. This does not mean that after 48 months, the risk is zero, it simply means that the disease-free survival line becomes primarily horizontal at that point. As Kathy's case indicates, no one should underestimate HER-2 positive breast cancer in the long-term.

I would, instead, look at survival in terms of all technology at your disposal, and based upon the facts underlying your wife's case. I believe that this is your approach and related question.

What options are available to a Stage IIB, node positive, ER-negative, HER-2 positive (I'm assuming positive through FISH testing)patient, who has been randomized to the control group in a Phase III Herceptin adjuvant clinical trial?

I believe that most of the information available with respect to this issue is anecdotal, but here are a few thoughts (most of which have already been commented upon by others below) --

1. OBTAIN MORE SPECIFIC PROFILING OF YOUR WIFE'S CASE: At the outset, you may want to see if M.D. Anderson can perform any type of gene profiling work to provide you with more information regarding your wife's case. I am familiar with one assay for node-negative, ER+ women known as Oncotype DX. Oncotype DX™ is a clinically validated assay that evaluates a tumor’s expression of 21 genes and quantifies the likelihood of a distant recurrence in women with node negative, ER positive breast cancer. I believe that M.D. Anderson has done similar work with respect to gene profiling for breast cancer patients (e.g., p53 gene overexpression, etc.). This is more in line with "statistics" again but at least it is in the form of results relating specifically to your wife's case.

2. "WATCHFUL WAITING": I believe that Kathy is at least one person who represents living proof of effective watchful waiting. Keep in mind that the www.her2status.com graphs indicate that between 50% and 58% of patients experience disease free survival after 48 months. So, as noted below, many of the women who are disease free are not posting on the board. If this path is choosen, please ensure that your wife has periodic scans to determine her status (i.e., both body and brain scans).

3. OBTAIN HERCEPTIN OFF-LABEL: You're simply not going to find herceptin off-label at a major established teaching institution. The concept at many conservative institutions is that it is hard or impossible to make a disease-free patient better by using more treatment; and conversely, it is possible to make them worse (e.g., cardiotoxicity with Herceptin). This takes us into the area of prevention.

There is currently no scientific evidence that Herceptin is "preventative" in an adjuvant setting. As you know, Phase III human trials are on-going at this point, and as far as I know, there is no indication as to when results will be presented. With respect to this point, the next major breast cancer reporting symposiums are ASCO in June, and San Antonio in December.

That being said, if you are trying to convince a doctor to use herceptin off-label consider making the following points:

a. Dennis Slamon has been quoted as noting that the biological activity of Herceptin, as tested in the lab, should be identical in every stage of HER-2 positive breast cancer.

b. Herceptin and Navelbine have been successfully used in a neo-adjuvant (i.e., pre-surgery) setting with similar response rates to those experienced in Stage IV HER-2 positive breast cancer (i.e., this is an example of effective Herceptin use prior to Stage IV).

c. Arguably, women with HER-2 positive breast cancer are at greater risk of brain metastasis (although this may be caused by longer survival with the advent of Herceptin), and the use of Herceptin sooner makes sense because generally Herceptin cannot penetrate the blood-brain barrier to battle such metastasis at a later point in time.

d. Herceptin is FDA-approved for advanced breast cancer. Although advanced breast cancer is generally thought of as "distant" metastasis, the fact that your wife is node positive is evidence of "local" metastasis. Arguably, node positive disease is a form of metastasis, albeit local rather than distant.

4. PARTICIPATE IN A HER-2 VACCINE TRIAL: In terms of HER-2 positive breast cancer prevention, there are several vaccine programs available throughout the country. At one time, a women who was node positive, could not participate in many of these trials but that is no longer the absolute rule (e.g., the Windber trial listed on the "clinical trials" message board). There are excellent programs located throughout the U.S., including University of Washington, Duke, University of California, San Francisco, University of Pennsylvania, and the University of Minnesota. Keep in mind that many vaccine programs will not allow participation if you have already tried herceptin or are not in a state of "no evidence of disease." So, be aware that obtaining Herceptin off-label may disqualify you from participating subsequently in certain vaccine programs.

Eugene, I have not made a recommendation as to which option is best for your wife. This is a personal decision and is best made after evaluating all of your available options.

I hope this helps.

Warmest regards,

Paul

Paul and others, many thanks.