early Christmas present--10 yr overall & bc specific survival results just published!

[AlaskaAngel]

The confusion is understandable, in part because it becomes less of a factual discussion and more of an emotional one.

Unfortunately, it is too easy to generalize about the effectiveness of trastuzumab due to the lack of scientifically based trials to demonstrate who benefits from the addition of chemotherapy and who does not.

Drug development customarily is done through testing a therapy upon a specific population, using specific characteristics and parameters for what demonstrates effectiveness and what does not. It then applies only to the specific population that had the specified characteristics required for the trial.

The original trials primarily were specifically designed not to include early stage HER2 bc patients with tumors under 2 cm or patients with negative nodes, and included the requirement for those patients who did qualify with those characteristics to receive trastuzumab AND chemotherapy.

Applying the results of those trials to the group of patients who were not included in the clinical trial and who were early stage then led to the unfortunate and UNPROVEN general practice of combining chemotherapy with trastuzumab.

There is uncertainty as to what extent the addition of chemotherapy is merited because of the lack of proof based on the combination therapy used in the first place as part of the clinical trials used to demonstrate "the effectiveness of trastuzumab".

There are those whose cancer simply does not respond to trastuzumab plus chemo. For that group, their chance to have some other form of therapy that IS effective for them sooner is thus delayed and damaged by the use of trastuzumab plus chemo.

Add to that the number of patients whose cancer remains in remission without trastuzumab but with chemotherapy.

Add to that the unidentified number of patients whose cancer would remain in remission without trastuzumab but who genuinely may have benefitted instead from some other treatment leading to menopause other than chemopause, such as other methods of ovarian ablation.

As long as we have infinite amounts of drugs and money to fund all the cost-intensive treatments and all the testing involved and huge loss of productivity, we don't do the homework to find out who benefits and who does not from which therapies. It is emotionally appealing, but poor use of resources.

We continue to apply blanket therapy to the broad group of early stage patients at great personal and general cost that would be better spent on patients that have been scientifically proven to benefit.

[Jean]

Amy,
I am not putting words in your mouth, nor am I starting a fight.
I am not in that frame at all.
When an article such as this one comes out with a ten year survival to 84% that is cause for celebration. No it is not a cure, no one said it was. To place a label it is not a cure is not fair to the report. I believe we all want a cure. Right?

You made a strong stand by saying, "I'd like to point out that early detection of breast cancer does not actually improve overall survival." I don't agree and that is what the forum is about.

You also wrote "not from "catching it early." But the ACS states,
The five-year relative survival rate for women diagnosed with localized breast cancer (cancer that hasn’t spread to lymph nodes or outside the breast) is 98.5 percent. (early stage).

I never wrote that not getting mammograms means you won't know you have breast cancer. I wrote that we have an obligation to ourselves, family and loved ones to take care of our health, which means yearly check ups...and that goes for all types of cancer.
Colon cancer, ovarian etc. Women (and men) need to have health maintenance. We don't know the numbers of how many women who have mammo's are told all is clear and then later to hear that they are dx. Yes, this happens, but it sounds odd that because there are false reports, does that mean we should drop the mammograms? Nothing in this world is perfected just yet.
My mammogam found a small 6MM cancer, I and many many other women are dx. with small early stage cancers. Maybe we should poll our forum and ask how many of us were dx. early via mammograms? That would certainly show some stats.
I am responding to the post to offer the other point of view that early stage dx. is a strong preference if one has to be dx.
We don't know who will advance and who does not advance.
Going back 40 and 50 years ago women did not have mammograms available. If we pull the stats from 50 years ago how many women died from breast cancer alone?
We have made extreme advances in technology and medicine.
Are we there yet? no sadly.
When reading your statement it is flavored with the feeling that early stage dx. did not have merit as you wrote early detection does not actually improve overall survival. I disagree and wrote what I wrote....do not take it on a personal level against you or a fight.
My thoughts are different than yours.
That is the essence of the site. To share thoughts, reports and promote support to all who are fighting the disease.
Sorry if you took my response as a fight.
Jean
_______________________________

[Jean]

I agree that a trial for early stage (which I believe is being conducted) would reveal some new data for us.

There is a trial for early stage bc without chemo/ just herceptin.

Jean

[StephN]

I just want to add that in my "neighborhood" in 1999, testing for HER2 WAS standard. Mine was determined by the IHC rather than newer FISH method.

There was a thread here many years ago exactly on the topic of HOW members' cancers were detected. There was a great number who found it themselves after a fairly recent mammogram. In my case I found a "lump" just three months after a clean mammo report which was accompanied by a letter warning me that I had dense breasts and should not forget to do self checks as often as I could.

I will go ahead and say in my case I attribute my long remission and continued life to Herceptin. But I am not everybody, and since I got Herceptin AFTER I was diagnosed stage IV, will point to its addition to treatment and long use of Herceptin alone as the trump card.

It pains me that more members here and women I know off this board did not get a better result with their treatment that included Herceptin or the other newer targeted treatments.

Better statistics are coming and just take so darned long to develop. In the meantime, most newly diagnosed would rather be safe than sorry. Or at least feel they are "safer."

[Jean]

Steph,
Thank you for pointing out the attributing factor of women with dense breasts, which places another issue all together. Like you, I had he same issues back in 90's. With unknown suspicious lumps in the breast.

My heart aches for those that have not had the results as you have experienced. For sure Herceptin took a huge bite out of this nasty Her2 and I am happy at the same time for that progress.

Herceptin has opened my eyes to see the glass half full. When I was dx. I was so frightened (natural reaction) I remember thinking Her2 OMG this is the worst news. Then doing my search I learned about Herceptin. Had to fight for it. Did it make the difference? I will never know for 100% but Dr. Salmon convinced me that all women should be treated.
With those feelings in place, I admit I am sensitive to the newly dx. women (like many others here) who come onto the site and are seeking information.
While we know Herceptin is not a fit for all, I have to agree with you that "rather be safe than sorry."
I am hoping the research will bring forth more trails for all the unknown moving parts to this disease.
In the meantime doing what we can to remain healthy and strong.
Jean

[AlaskaAngel]

Reassurance is a comfort at time of diagnosis. Sometimes we would rather be reassured than pursue a higher degree of truth upon which to base our trust.

What is cruel about that is the professional endorsement of practices based in part upon of the failure to demonstrate proof of efficacy of therapies recommended, which plays upon our hopes, and results in the diversion of much of the limited resources.

It may sound hard-hearted because we do care about each other's feelings and like to reassure each other, but do we want to focus our limited resources on reassurance regardless of efficacy and cost, or do we want to focus them upon efficacy?

Should we continue to encourage the professional practice of shotgun application of combined therapies through the failure to demonstrate proof of efficacy by clinical trial? Have we seen clinical trial proof offered by professional direction, demonstrating whether or not there are early stage patients who maintain remission through the application of trastuzumab when used as a single agent? Or are we continuing to see earlier and earlier stage patients still being "professionally" offered the shotgun combined therapies?

As mentioned, there is a trial of the use of trastuzumab without chemotherapy. Will it provide proof of efficacy for most early stage patients, or will it provide proof only for elderly patients (who do not require chemo in addition as one method to bring about the hormonal changes of menopause)?

[Jean]

AA and Mtn.
Why not address your statements to Dr Salmon and have him respond. I think he would be the best person to respond to your positions regarding herceptin and mammograms.
I have his email.....let me know.
I would truly like to read his response.
I admit, I was reassured by Dr. Salmon that Her2 TCH was the correct treatment for me.
His exact words...."you saved your life by NOT listening to the dr. in New York, as they have missed the boat." This was in 2006. Dr. Salmon's trial of TCH was not published at this point when I consulted with him. I do not remember him saying it would work for everyone of course. But the trail showed impressive and compelling results. For me I know it is not reasonable to think a cure would work 100% for every single person. Our chemical and biological make up as humans is vast. Similar to when antibiotics work for some and not for others. There are thousands of vaccines and drugs that work for a major group but there are always a sub group that does not benefit.

Limited resources, by who standards? Dr. Salmon was able to obtain the funding for his research. Those monies were donated by organizations that believed in his research. Who expected that herceptin would work for 100% of the population? This was based on the facts that Dr. Salmon presented for his research, not on reassurance. The only reassurance Dr. Salmon offered was his strong educated opinion as a researcher to tell me that TCH was the cutting edge and to certainly have the treatment. Good enough for me. I can honestly say I knew going in there was always the risk, and also the chance I could recur in a short time and maybe in the future. I could also die of something else.

I think this entire discussion is valid since it comes up often on the site.
If you are not comfortable to reach out to him I will be happy to send him your thread and ask him to respond with your permission since it is your thread.
I am just tried of the same old beating up the what if's of herceptin and what the research did not do. But it is valid like I said, so why not hear why the resources are being wasted from the mouth of the research man himself?

This life as we know it today right now offers us no guarantees.
I don't believe in Santa, the tooth fairy or the Easter bunny, but I do believe in Dr. Salmon. I am not a emotional wreck who requires reassurance. I wanted facts to make a health decision based on what we do know. We knew herceptin was working for some.

I still take the position that when a women is dx. those early days regardless of stage do need reassurances. By that I mean, not pie in the sky reassurances, of course telling the accurate truth that herceptin is a game changer and a wonderful life saving drug. We know it doesn't offer a cure or is 100% promise.

I focus on the many who have had positive results, certainly not turning a blind eye to the facts. Again, medicine is also an Art not just a science.
Just like those arrogant doctors who become annoyed with a woman who asks too may questions or are too upset to suit him. He dismisses her, as he can't or won't take the time she may need, because she is upset. How often have we read this on this forum? That is a dr. who is sour and more than likely could use a lesson in bed side manners. Or maybe he just has too many sour grapes under his belt.

I am sorry but it sounds like sour grapes to me.
Again, lets put it to the researcher and see what he has to say about the research plus costs and effectiveness.

Jean











Jean

[Jean]

http://video.pbs.org/video/2365362396/

Mtn. posted this link to the video.
These talented people have hope and are using drug that do work for some and not others. Are they wasting money, time for those that it doesn't work for?
I look forward to viewing this when it airs.

[AlaskaAngel]

I'm looking forward to seeing the upcoming documentary too.

It is meaningful to provide encouragement for those who just want to be told the treatment will work (whether it actually will for them personally or not), because treatment has improved for many HER2 positive patients.

But maybe there is room for some genuine practical support of the group of people who have done that same extensive, expensive and difficult treatment with no personal benefit at all? What do we say to help improve their situation? "It really is too bad.... that treatment is a miracle for some like us, you know.... even though many early stage patients never needed it at all, it is a great idea to continue to throw their money and time away.... it never did work for everyone... maybe someone will figure it out someday, somehow.... it is okay, you did your best... maybe you'll be lucky enough to find the right combination in time... best of luck... stay in touch?"

[AlaskaAngel]

As a HER2+++ 1.9 cm tumor patient who did chemotherapy, rads, and a very short run of tamoxifen and who remains NED at 12 years out, I wonder why there have been no clinical trials offered to me and those like me, to see if our tumors and genetics can help to identify any reasons that would then support a way to identify other patients who don't benefit from trastuzumab.

Likewise, I wonder why no doctors have created any trials for those who received a recommendation to do chemo and trastuzumab but have opted to do trastuzumab without chemo and who have remained NED, to review their tumor characteristics and genetics to see if that would provide actual proof, as opposed to failing to seek and utilize any information from such patients.

We are out there. I have never seen any indication that anyone ever suggested or tried to do it, in genuine practical support of those who do not get any benefit from these difficult and expensive drugs + all the support testing and medications they require.

[sarah]

Herceptin saved my life and is the reason I'm still alive. In 1999 I was diagnosed with HER2+++ BC but they called it DCIS and said Herceptin was not necessary even though I wanted it. 4+ years later I was diagnosed with metastatic bc HER2+++, it looked very grim. I was sure I was a goner but with taxol and Herceptin for 6 months then Herceptin and Femara for 6 more years, I'm here today so I can say confidently that I proved that for me, Herceptin made the difference - without the Herceptin (despite a mastectomy that I was told was over the top), my cancer came back, with it, I'm here today.
I have had heart problems and damaged lung but both due to radiation and not the Herceptin (my every 3 month sonograms for the left ventrigal were always very good). So I lift a glass to Herceptin and thank Dr. Slamon for continuing despite losing his financing from Genetech and proving to Genetech and the world that Herceptin is a great drug and profitable. I hope he never has to beg for research money again. Thank you Dr. Slamon and the Tartikoffs. Watch the movie "Living Proof" about him and Herceptin, it will bring tears to your eyes.

[JessicaV]

I think it is important to understand drug resistance when it comes to Herceptin and its sister drugs. The reason why these drugs stop working for many HER2+patients ie on HER2+ tumors or tumor cells is that when the drugs block off pathways that the tumor cells initially use, the CST tumor cells can mutate to form daughter cancer cells that use other pathways. Thus they get around the "blockades" created by these drugs.

Perjeta blocks different pathway/s to herceptin, so if both drugs are used at once, the chances are higher of killing off all the cells before the CSC manage to mutate into something that uses yet another pathway.

The researchers of one study into CSCs and metastatic processes recommend that eating brassica, tumeric, soy, and green tea all help knock out relevant pathways and interfere with tumor development too. If they can get a big enough bunch of these type of drugs together, blocking enough of the main pathways in one go, and the resistance issue is going to be a lot less of an issue, and blanket treatment for all HER2+patients might be so clearly effective that the equation becomes simple.

In time there may be vaccines to fix the tumor suppressors that stop working and that might be the treatment of the future. But in the meantime, I am very grateful to have been treated with Herceptin which my onc said has changed my 5yr survival chances from 45%(with surgery only) to 92%

[AlaskaAngel]

I believe that many of the people involved in bringing trastuzumab to us are to be admired and appreciated for their initiative and hard work.

To the degree that they have no control over the unfortunate blanket application for the various patients for whom the the mandated combination of drugs do not provide benefit and yet is the only option authorized, they should not be blamed.

The firsthand, anecdotal information and explanations I think are very helpful for anyone to consider. That includes my own anecdote.

Since the original trials led to blanket use of therapies, and since I did not have trastuzumab and yet I remain NED, it is reasonable to continue to question just exactly what therapy or combination of therapies did the trick for any of us. Can we know for absolute certain which therapy given made the difference for each person? Is it proof?

For some, it is possible that becoming menopausal through the use of the required addition of chemotherapy is what then slowed their rate of metabolism and would be enough without the other drugs.

Since I had a very aggressive, strongly HER2 positive 1.9 cm tumor (grade 3) and yet I never had any trastuzumab and continue to remain NED at 12 years out, what we DO know is that trastuzumab is not the reason that I remain NED.

It also especially poor practice to continue to pressure patients and the doctors treating early stage patients to push their patients to include chemo in order to receive trastuzumab, since the trials done for this group were done largely only for those who had positive nodes or tumors at least 2 cm in size. We cannot say who benefits from which therapies.

If it is true that becoming menopausal is adequate treatment for some to be able to remain NED, there are less invasive ways to accomplish that, which should be offered as alternatives instead of pushing chemo as the ONLY way to do it (in combination with trastuzumab).

It is true that chemo MAY also reduce the number of cancer cells when the type of cancer cells one has happen to be very responsive to the particular chemotherapy being given. At the same time, we do not know what mechanisms of the immune system are being suppressed by the chemo that otherwise could provide significant benefit to patients for whom other therapies (such as trastuzumab) when used alone would have been more effective. For early stage patients, this may be especially true in that therapies are often more successful when the tumor burden is less -- which is the case with early stage patients. We cannot know because the evidence was not obtained for this group.

These is is all pertinent information that should be provided to early stage patients. Instead the sledgehammer approach continues for this group, even though these patients have not had the opportunity to base the conclusions on carefully trialed evidence.

I do understand that trials cost a lot of money, and that the financial bias against providing money for any trial for this group exists, and that trial results could reduce the present policy of over-use of very expensive drugs. The bias is significant because the drugs are so expensive and revenues from blanket application are not insignificant. Who would fund such trials just because that is a more ethical, less harmful thing to do?

[JessicaV]

Hi Amy, you say that early detection does not affect survival rates. This is something I keep hearing quoted. It interests me because it is counter-intuitive, and I decided I would like to explore it further in order to understand the issue properly.

When I did a search on the research into correlations or the lack of them between early detection of breast cancer and survival rates, what I found was a study published in 2007/8 called "An overview of prognostic factors for long-term survivors of breast cancer" (A review of the PubMed database from 1995 to 2006, also using data from long-standing Eindhoven Cancer Registry summarizing available knowledge on the determinants of survival 10 years or more after breast cancer diagnosis.) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217620/

"Trials on population screening have reported 21–29% reduction in BC mortality for women invited for screening within 14–16 years of follow-up [19, 97]. Screening identified tumours at an early stage consequently, survival improved [98, 99]"

"Conclusions Effects of traditional prognostic factors persist in the long term and more recent factors need further follow-up. The prognosis for breast cancer patients who have survived at least 10 years is favourable and increases over time. Improved long-term survival can be achieved by earlier detection, more effective modern therapy and healthier lifestyle."

This is different to the information you have found. Maybe these different research projects deal with different populations (this one only looks at woman who have survived 10years post diagnosis). Maybe they are talking about statistical significance not being reached. Maybe the research design affects the results. Or maybe there are changes happening with time so what is true in 2007 is not true at the time of the research you are referring to (which may be earlier or later).

Would you mind giving the links to the research that says that early detection makes no difference to survival, so we can start to look together at these different bodies of evidence and discuss them? I am not trying to tell you that you are wrong, just inviting you to be part of a joint process to help get to the bottom of this discrepency.

[JessicaV]

I sympathise with the concern about having to have chemo too if you want trastuzumab, and the principle of a blanket treatment for all that is not fine-tuned to the best needs of the individual patient.

I think part of the reason for this is that the only treatment regimes the oncologists can offer with any sort of confidence are the ones that have been tested out on hundreds of people over quite a few years ie in large trials. If the oncologist changes any part of the regime from what was used in the trial, they are immediately using a totally untried treatment which could be either useless or dangerous. When they stick to what has been shown to be effective for someone like the patient in question, they can know a lot more about what side effects to expect, what tests to administer etc. They know the chances of it working to get rid of the cancer in question. My onc says that reducing dosage of anticancer drugs to less than 86% of the recommended protocol significantly reduces effectiveness.

The other part of the problem is that ethics committees who have to approve research trials (I understand the FDA uses this process though maybe they call them something different)generally will not permit any trial to start unless it offers all participants a good proven treatment. So it would have been initially hard for researchers to get approval for a herceptin-only treatment, until the drug becomes so well recognised as a good proven treatment on its own for patients with a particular kind/size/etc of tumor. In their wish to protect us the watchdogs slow down the approval of the sort of treatment you advocate.

The more different trials are done of different combinations, and the more the researchers manage to trial different protocols/regimes of drugs etc, the more options they can use with reasonable confidence they will work.
Carboplatin and Taxotere were used together with Herceptin in the big trial that finally proved there was a good chemo alternative to the heart-damaging andriamycin type drugs. Those particular chemo drugs were chosen because there were helpful interactions between them and herceptin and the HER2+ tumor that made the combination more effective. They were not just picked at random.

[Debbie L.]

Great discussion.

I agree with AA on both her points. We need more evidence to know what to do with very small HER2+ primary cancers, and we need to dial it down so that we give anti-HER2 therapy in the most targeted way possible (knowing who is most likely to benefit and from which anti-HER2 tx). One of the "problems" with figuring out how to manage the very small (say, under 0.5cm) primaries is that the recurrence rate is so low that it requires huge studies that take forever to get results. And then, even if we do get results, by the time we get them there are many more options on the table (for example, Kadcyla, Perjeta, etc).

It's easy, with hindsight, to say that a certain treatment (Herceptin is the best example), should have been approved sooner. But as others have said, it (alas) takes a long time to prove that a treatment is both effective and safe. In addition, the old style of taking a big group of cancers and just seeing if "x" is better than "y" is no longer enough. Most if not all of the newer trials are collecting as much data as they can -- markers, immunoscores, gene assays (of both the cancer and the host) etc., to attempt to tease out how to predict who will benefit. This can eventually spare both the toxicities and cost of treating those who won't benefit -- while also spurring research into finding new treatments for them.

I also agree with Mountain Girl about mammography. It may have a small benefit, but not nearly as much as we've been led to believe. This debate has been going on for a long time. There are many studies showing no benefit (no improvement in survival) for those whose cancers were detected by mammography vs. those whose cancers were detected by other means. Even the positive studies (showing benefit) show only a small benefit (and some harms). There are lots of reasons for this fact, including that it's the slower-growing, less deadly cancers that are most likely to be detected by mammography. Also, it's tricky (perhaps impossible) to figure in the improvements in treatment and know for sure whether improved survival can be attributed to earlier detection or improved tx (or both). Someone asked for the evidence -- here is one fairly-concise summary, with references: National Breast Cancer Coalition Statement on The Canadian National Breast Screening Study

No one person can state that "x" (mammography, Herceptin, whatever) saved her/his life. Although, those with stage IV HER2+ disease and long NED-ness can certainly make a good case for the argument (smile).

I'm putting my hopes on the immunotherapy research -- not just vaccines, but ways to trigger/control/direct immune responses in more global ways. Our knowledge about it is increasing daily. The bad news there is that with each increase in understanding, the incredible complexity of immune function becomes more evident. But still, I believe that it has potential both for primary prevention and for preventing or controlling metastasis.

Debbie Laxague

[Jean]

Debbie,
Thank you, well said.
We are doing all that is possible at this time.
This is a complex disease and I strongly doubt that the research is being ignored as to the why's.

[Jean]

Debbie,

The report went on to say that “…while the incidence of early-stage breast cancer increased significantly in the period between 1976 and 2008,

I was dx. early sage small tumor via mamogram.
For me and the others who were dx. early I see the beneift of the exam.

The report continues:

The incidence of late-stage disease decreased only slightly and the incidence of metastatic breast cancer did not change at all.1 More data continues...

Debbie - I would ask - was this group - their first exam?
Or had they been going on a yearly basis?

I had been having mammograms exams on a yearly basis. Having had dense breast it helped during those years to track any changes in the breast.

While I have to accept the report I still need more information on the groups that were early dx. and those that were later. Have lots of questions.

Thank you again Debbie,
Jean

[Jean]

Just to clear up any misunderstanding:
I also would have enjoyed having everyone have a positive results with herceptin. The flavor of the thread was reading as if the research community had abandoned those cancer patients who did not have positive response. Which is certainly not the case.

Or the research is not doing their job since some failed on Herpcetin and they should know why and why now.

I am looking forward to the documentary which will hopefully offer some clarity to the debate over the issue. Hopeing it will deliver information on the research and how hard the medical industry is working to find a cure.

For those of you who were able to see Vice and the approach of the current treatment shown, new doors are opening, as soon as next year. Will that work for all of the cancer population?

This thread began with positive news and moved to another level.
So be it, but let's not forget the good progress. We have a long way to go indeed and we all want everyone to be treated with drugs that offer a positive results to all.

[AlaskaAngel]

One negative and very likely factor/probability affecting the question regarding mammograms is that in wanting to "think positive" about this question, we also tend to want to disregard the knowledge that radiation itself to a degree is known to be a cause of cancer. To what exact degree the low level of radiation used for mammograms causes cells to malfunction is the question, but we can't entirely discount the likelihood by wishful thinking.

In addition, in reality we are subjecting both those who actually get breast cancer in their lifetime (is our guess at that at present 1 in 3 women???) as well as the 2/3 who never are formally diagnosed with it. Those who are diagnosed with it, logically, receive far more radiation over time than those never diagnosed with it.

So, in considering both the positives AND the negatives about current professional recommendations for mammogams, the question quite possibly would be, how many original occurrences plus recurrences are due to the steady/increased exposure to radiation, as opposed to how much benefit we get from detection by mammograms and other radiation exposures.

Two-thirds of those receiving mammograms are not diagnosed with bc in their lifetime and get essentially no benefit from having them (other than periodic reassurance by them, and any incidental diagnosis of other problems that a mammogram might expose).

A.A.