Okay I need to vent here it goes....

[sarah]

in 1999, I asked the oncologist about my HER2+++ reading and was told, like you I didn't need Herceptin because my cancer was DCIS, I was also told I had clear margins about a mastectomy and didn't need chemo or radiation. well, then it came back in 2003 as invasive. I had read up on herceptin in '99 but all the doctors said no.
today i wouldn't be so trusting.
sarah

[AlaskaAngel]

Hi Jean,

Your post is letting all of us vent, and hopefully that is a good thing.

I have very mixed feelings that are very much in context with where I fell in the timeline for the recommended treatments.

No one was routinely being tested for HER2, or treated for it routinely with trastuzumab when I was diagnosed. My surgery was done at a major cancer center and tested for HER2, but those results did not come back until sometime after all the other results were back, and I was never given the results for the HER2 testing. My onc neglected to even provide standard discussion about treatment, partly I think because I was primarily treated in Alaska and not at the cancer center -- and my PCP believed the onc had covered all of it with me while I was in Seattle. So I didn't know I was HER2+++ by IHC until I was almost 2 years out.

When the success of trastuzumab was announced, I and a lot of other HER2 positives were hanging off every bit of news, waiting to hear anything about what it meant for those of us who hadn't been in the trial. There was ZERO information provided to us.... day after day, week after week. We had to hear over and over what a "miracle" drug this was, and how "all HER2 positive patients now were going to benefit from this drug", but at the same time the actual result was limited to "all newly diagnosed HER2 patients". To us that clearly said loud and clear that even though our risk was identical to the risk for those who were newly diagnosed or even greater than some newly diagnosed with smaller tumors, etc., we were left in entirely in limbo. It was as if we simply did not exist to the oncology community. They didn't even have the humanity or wisdom to talk to us at all. How could that build any trust in what they are doing?

Eventually the information was provided to indicate that because we'd already had our chemo, we "missed out" because Herceptin "works better" with chemo (although there was no information provided as to the technical basis for this justification. And while I am at it, can anyone here explain more precisely why it works better with chemo?). At first the recommendation was that anyone who was within 6 months of completing chemo would be eligible for trastuzumab, and later that was changed to within a year of completing chemo.

No one has EVER explained why trastuzumab was not recommended for all of those people who were less than 2 years out from chemo. Considering that we are told over and over that HER2's are at greatest risk during the first 2 years, what sense could it possibly make to deny those who were over a year out from chemo and less than 2 years out the ability to have trastuzumab?

I was past 2 years out at the time. My onc was willing to provide but not in favor of it. A second opinion from the same major cancer center was the same. I chose not to have it.

I am 6 years out and so far, still NED. I know there is a percentage who get it and think they are benefitting from it even though they get no benefit. I know there is a percentage that fail on it. I'm glad that so many here have benefitted from it. I too find it appalling that for some the testing for HER2 still apparently is not routine.

I have very mixed feelings about how the oncologic community has responded to those of us who are HER2 positive.

[Joe]

AA,

The initial criteria used in the adjuvant clinical trials included the "2 year rule". BUT there is nothing in the Herceptin Labeling or "boxed Label" which places this restriction on patients. It is solely up to the prescribing oncologist:

Here is the "official" labeling

http://www.gene.com/gene/products/in...rescribing.pdf

Regards
Joe

[dlaxague]

At diagnosis in 3/2001, I was told that the bad news was that the cancer was ERPR- and HER2+. The good news was that they were enrolling in a trial of adjuvant Herceptin. I did enroll but did not get the Herceptin (control arm). Losing that toss was the hardest blow of the whole experience, although now I've mellowed considerably about it, being still here and NED.

I've been listening to these podcasts (bcupdate and oncology unplugged) and I'll have to go back and see who said what and quote them properly, but the discussion was about topoIIa, HER2, and anthracyclines. A statement was made that for HER2+ topoIIA+ cancer, an anthracycline probably offered an equal benefit to Herceptin. HuH?! I'd heard it the other way round from Dennis Slamon - that if Herceptin is used, an anthracycline offers no added benefit even for topoIIa+ cancer. But said that way - it could well be that I had a topoIIa+ cancer (it wasn't tested for) and that the anthracycline trumped the no-Herceptin and that's why I'm here. Or not - no way to know for sure. But still, I liked hearing that.

AA, as I understand it, what they are saying about not giving Herceptin without chemo is two-fold. One, they do know that with some chemos, the effect of the two together is synergistic (stronger benefit when given together than the sum of the two given separately). In addition, this is the era of basing decisions on evidence. Evidence based medicine, as we see here, has its strengths and its weaknesses. There is no evidence for giving Hercptin alone in the adjuvant setting. Some oncs are more cautious than others when it comes to evidence to support their recommendations. Some have been burned, jumping on a bandwagon before the evidence was in (stem cell transplants for breast cancer was the biggest and worst example of this - read "False Hope" by Rettig). So I understand their caution. And then there are the insurance companies, usually quick to point out lack of evidence and thus deny coverage, especially for something as expensive as Herceptin. (have you noticed that it's really hard to type "Herceptin"? It goes against some principles of the fingers somehow - mine really want to put the "p" after the "c", and/or add a "g" at the end)

Debbie Laxague

[AlaskaAngel]

Joe: Thank you for that info, as it is new to me. One other problem for me was that I specifically asked my oncologist at the time about clinical trials, and even though HE knew I was HER2 positive he did not mention the trial to me since I was both node-negative and under 2 cm (not eligible for the trial). A patient can be asking the "right" questions to the best of one's ability and still be left out of the loop....

Deb: As I understand it, TOPO IIA testing doesn't require a fresh sample, and someone did post recently that a test for it has been approved... You know quite a bit about the process behind clinical trials, and I am wondering whether it would provide reasonably important information to collect a representative group of those of us who "missed out" on traztuzumab and test us to get more of an idea how relevant TOPO IIa testing actually is? I gather that about 1/3 of HER2s would be TOPO IIa? Wouldn't it also help in deciding whether (or not) to do other therapies? Wouldn't it also provide some insight into whether there are HER2 positives who both did not get trastuzumab AND are not Topo II and have not recurred?

I definitely have followed the questionable treatments and understand the need for caution. But evidence-based medicine stumbles around when trials for nontoxic treatments are subordinated to established toxic regimens that are already known to work for less than 20% of the people recommended to receive them.

What they do not know is 2-fold:

1. The effect of chemotherapy may be stronger initially, but since chemotherapy effect only generally holds for around 5 years (and the evidence long-term for trastuzumab with or without chemo is not yet in), having adjuvant trastuzumab "late" without chemo may in fact be MORE effective in that the combination treatments in that the immune system has not been damaged (not to mention, the patient has not been left carrying an extra load of fat from the drugs like steroids that are given with chemo, and thus MORE predisposed to recur).

2. Is there any technical explanation after multiple years now of why chemo given with trastuzumab would actually be more effective?

[dlaxague]

>AA said: Deb: As I understand it, TOPO IIA testing doesn't require a fresh sample, and someone did post recently that a test for it has been approved... You know quite a bit about the process behind clinical trials, and I am wondering whether it would provide reasonably important information to collect a representative group of those of us who "missed out" on traztuzumab and test us to get more of an idea how relevant TOPO IIa testing actually is?

I don't know, AA. If Slamon is correct, it would mean that at least in countries where Herceptin is available, topoIIa status is a moot point (ie: not relevant at all). He uses it only to make his case that anthracyclines have no place in current treatment, when he shows that the stats that appeared to show an increased benefit of anthracycline for all breast cancer, or even for all HER2+ breast cancer, were not truly showing it for all. They were reflecting a large increased benefit for topoIIa+ cancers and none at all for the rest. The increased benefit in that small group was strong enough, however, to skew the stats for all. And at that time, we didn't even know the subgroup existed. (I wonder how many other subgroups we'll learn of over time - that we don't have a clue about today).

I wondered if there might be some link between topoIIA+ and response to Herceptin, since there seemed to be no subgroup of Slamon's cited studies where there was an additional benefit for an anthracycline with Herceptin, even though we know that only about 1/2 of HER2+ cancer responds to Herceptin. So in that 1/2 that doesn't respond, shouldn't we see 1/3 of that 1/2 (1/6 of all HER2+, if it's randomly associated) who did get an additional benefit from the anthracycline? Maybe it's too small a group to show significance, or maybe being topoIIa+ has something to do with Herceptin response? I'm sure that they looked at that, so the answer must be - no association between topoIIa status and Herceptin response.

I wish that I knew more about clinical trials. NBCC has a Project LEAD course on clinical trials, held every two years, and I think it begins in early November. Is anyone on this list attending?

> AA: Wouldn't it also help in deciding whether (or not) to do other therapies? Wouldn't it also provide some insight into whether there are HER2 positives who both did not get trastuzumab AND are not Topo II and have not recurred?

As I said above, I don't think that it has any relevance, if Slamon is correct. Again, most any information about those who didn't get Herceptin is now moot, in our country at least. I would be interesting to those of us who didn't get it, but the information would have no practical application. That also applies to discussions of "late" trastuzumab. Science has moved on (and left you and me in the dust).

I'm curious (if you don't my telling us) why you did not take your onc up on the offer to do late Herceptin? Was it cost? Or some other hesitation?

I'm not sure what you're asking when you ask for technical information about why trastuzumab works better with a chemo. You mean the biological/cellular explanation? I don't know. It would involve one of those complex growth pathway diagrams that make my head hurt. And as far as synergy, I don't know that they do understand the phenomenon at cellular level - they are simply able to measure it from clinical observation. But I could be wrong.

Do you remember in the movie, Slamon/Connick said something about Herceptin being able to keep disease stable but not able to shrink it? Maybe that's why it's better with a chemo? Most of the targeted therapies (Avastin, Tykerb) seem to work better, or work only, with a chemo. I don't know the answers. But the questions are interesting.

Debbie Laxague

[Marilyn]

I am finding this very interesting. I was diagnosed in Feb. of 2000 and my surgeon is the one who told me of my Her2 status and that it was an agressive cancer but the good news was that there was a drug, Herceptin, specifically for my kind of cancer. After meeting with my oncologist I was devastated to learn that I didn't qualify for that trial. My tumor was too close to the chest wall and that excluded me from the trial for patients who were not metastatic. At least that's what I understood at the time. I talked to someone at the Oncology office about this and she told me that the good news was that I would get the drug if I had a recurrence. At the time I thought, no, the good news would be if I never had a recurrence. I had that recurrence and started Herceptin along with Taxotere in July of 2001. I have always been grateful for Herceptin and the timing of the drug for me but after watching the movie I'm even more grateful!

[Catherine]

Love and thanks to all those that have gone before us. I taped Living Proof and have only watched half of it. I think it is very well done. Thank goodness for Dr. Slamon and those that have struggled thru the science and trials in order to advance treatment for all of us. I, too, feel like one of the lucky ones. I had a bioposy on a Tue in April 06 and in less than a week I saw one of the best surgeons in town. She told me all about Her2. I was clueless. She referred me to an excellent oncologist. They all told me right away (April 06) that I would be having Herceptin. Knowing what I know now, I am so thankful that Herceptin was prescribed for me without question. I would not have known enuf to ask for it. My other thanks goes out to Tricia K in Ireland. She found me snooping around the Komen site for info about Her2 and directed me to our site. I am a lucky woman. Thank you all for sharing your wisdom and support. What a wonderful group of people.

Hugs to all, Catherine

[harrie]

Did I read correctly that herceptin actives the immune system? If so, how does it do that?

[Christine MH-UK]

So far, everyone has said that they got their her2 result soon enough.

There can be problems because of shortages of people to do the tests. According to a doctor I met at a party (who did not know that I was a cancer patient), the government put in very hard standards for the test interpreters with harsh penalties for people who failed the tests. As a result, people focus on just qualifying to do one test. This doctor had worked on the European continent before and most people there had one main test they did and one or two others that they did as needed. Major problems can arise if something happens to the person who is qualified to do the test. I was in chemo with the woman who did the BRCA1/BRCA2 tests and she couldn't even get herself tested because she was THE person who interpreted the results for a wide area.

It will be good to know where the her2 test is still a problem so the blackspots can be sorted out and I have told people to keep a look out for this.

[Becky]

Herceptin activates the immune system because (in theory) the herceptin attaches to the outside of the cancer cell preventing receptor crosstalk (which leads to reproduction). So, the cancer cell is just hanging out not being able to do anything. Some cancer cells will die a natural death. Others are theortically killed by the immune system because Herceptin is an antibody that is "non self". The immune system attacks "non self" things so the immune system attacks the Herceptin (which is attached to a cancer cell) and anniliates both.

[dlaxague]

>Becky said: Others are theortically killed by the immune system because Herceptin is an antibody that is "non self". The immune system attacks "non self" things so the immune system attacks the Herceptin (which is attached to a cancer cell) and anniliates both.

Thanks for the understandable explanation, Becky. So is that also how heart cells can be damaged? By the person's own immune system which is tricked into attacking the heart (whose cells have lots of HER2 receptors also)?

This also reminds us that the immune system does not recognize successful cancer. It's not the immune system that it as fault, it's that successful cancer is extremely clever at finding ways not to alert the immune system. The think that sometimes it can even recruit the immune system to help the cancer establish itself and/or grow. All the talk of "boosting the immune system" to fight cancer is on the wrong track, because of this fact. You can have the most robust immune system in the world but if you have a wiley and clever cancer, your immune system will bop on, heedless of its presence or even unwittingly assisting it. That's why vaccines might work - to try and trick the immune system into recognizing the stealthy cancer, so it will attack it. The cancer cells that you hear about that "everyone has in their body every day", that are killed by the immune system - that's true. Those cancers did not have that lethal ability to escape notice by the immune system. They were not a threat to life, for that reason.

Debbie Laxague

[Becky]

A few comments that are just my opinion (but based on a variety of facts).

I think the immune system doesn't recognize some established cancers because they have alot of "self" because they are from you and not from the outside. However, there are also alot of studies that cancers can and do camofauge the immune system but perhaps the "helping" effects of our immune systems is because of the "self" theory (which is my opinion).

Secondly, when the body doesn't get rid of that first pesky cancer cell I (again, my opinion) think its other mechanisms besides the immune system. It may have to do with the function of organelles (like mitochondria) in the cell that are faulty and perhaps cross talk between cells that goes awry. For example, one function of the mitochondria is to give signals for abnormal cells to undergo cell death OR signals to the chromosomes (or specific genes on the chromosomes) to fix the abnormality. Perhaps the fixing part isn't right - it is partially fixed and the cell can continue to survive and then reproduce (perhaps this is the first stage of getting cancer - aplasia, then hyperplasia, then dcis etc). The first steps may be that the cell and cell environment may not recognize that first small change and fix it. This would make some sense since cancer is (primarily) a disease of older age. Also, I want to say that cell environment could benefit one thing happening over another. Examples of this would then (or might) be impacted by environmental factors. Let's say you are overweight and don't exercise - you might have more estrogen or insulin growth factor bathing cells which could influence the "fixing" factors. Omega 3/6 balance etc. Please do not misconstrue that I am implying that we caused our own disease at all. Our own genetics are at play BUT studies have indicated that foods, vitamin D, exercise etc can prevent cancer to begin with and reduce recurrence. We have learned a balance omega 3/6 does the same etc, etc. Therefore, there can be some creedence in "manipulating" the cellular environment to help ourselves. Even HRT is a negative manipulator (for example).

I am just talking out loud here. I like to think I can have alittle more control of my own fate (both present cancer that I know I had and any that might have been).

[MJo]

This is a great place to vent. And it doesn't blow up the board. I am one of the lucky ones. I was diagnosed in late October 2005, when info about Herceptin and Her2 was heating up and this board was available. I had an aggressive oncologist who helped me get a free Oncotype test and who recommended Herceptin. I am grateful.

[AlaskaAngel]

AA: Wouldn't it also help in deciding whether (or not) to do other therapies? Wouldn't it also provide some insight into whether there are HER2 positives who both did not get trastuzumab AND are not Topo II and have not recurred?

Deb: As I said above, I don't think that it has any relevance, if Slamon is correct. Again, most any information about those who didn't get Herceptin is now moot, in our country at least. I would be interesting to those of us who didn't get it, but the information would have no practical application. That also applies to discussions of "late" trastuzumab. Science has moved on (and left you and me in the dust).

AA: Why do you think that finding out if there is a subgroup with possibly unique characteristics that require no therapy at all would only be interesting to those of us who have not recurred, and that finding out would have no practical application to current or future HER2's? Why would you believe it is not worthwhile to question whether or not there is such a subgroup? Are you assuming there is no such group without investigating whether there is or not?

Deb: This also reminds us that the immune system does not recognize successful cancer.

I don't agree that this has been proven. It very well may recognize cancer and succeed in keeping it at bay for most people, and fail only in certain subgroups with particular characteristics. It may continue to work to a significant degree in slowing cancer in those who have "more favorable characteristics", including characteristics other than those that are genetic (such as eating and exercising and not smoking, etc.)

I'm curious (if you don't my telling us) why you did not take your onc up on the offer to do late Herceptin? Was it cost? Or some other hesitation?

Probably for the same reason I don't depend on winning the lottery, or on the majority of our politicians to use common sense in dealing with economic buyouts. It had little to do with cost, other than a personal reluctance to devote such a big chunk of health care resources to a 50/50 chance (and only stage I at that) for being fortunate enough to have good health care insurance.

A.A.

[RobinP]

Here We Round Around The Old Issue Of Late Herceptin And It Still Stinks. AA., You're Right There Never Were Any Direct Answers To Those Who Missed Herceptin And That Sucks.

I Had To Research Late Herceptin Until I Drove Myself Nuts Where I Finally Decided I Needed It, After Being Kindly Counseled By Neil Spector- Expert On Her2 Pathways And Lapatinib Innovator And Director Formally Of Gsk Labs. I Pray It Was The Right Thing For Me AND I DO BELIEVE GOD LEAD ME TO THAT CHOICE.

PS. JEAN, ME TOO, YES, I DID HAVE TO CRY TO MY LOCAL ONCOLOGIST IN ORDER TO GET LATE HERCEPTIN... IT WAS A REAL FIGHT AND PLEAD FOR MY LIFE.

[hutchibk]

When I was dxed in '03 - I was almost the perfect candidate for Phase III trials, (but I would have also been randomized...) however we could not get a clear enough picture of 'something' on my liver, which turned out to be only hemangioma. In my case, sometimes no-one or nothing is really to blame, just is what it is. Consequently, I didn't qualify.

I wasn't entirely sure I really understood what the trial would entail anyway, and what it would really do for me, even though my onc did a great job of explaining it to me. I was just too green to "get it" at that point.

When I recurred 15 months out of treatment, my onc presented me with Herceptin as a great opportunity. I loved him for that. He still says that we have a lot of opportunity with Herceptin and here I am on it for my second time, this time as a double targeted approach with Tykerb. I would love to kiss both Dr Slamon and Dr Spector, and someday I hope I will get the chance. I also hope to enjoy the opportunity of Herceptin, Tykerb (and whichever new targeted agent is in the pipeline) for a very long time to come!


(where Dr. Spector is now: http://inside.duke.edu/article.php?I...ParentID=14669)