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Old 06-05-2007, 12:11 PM   #1
Christine MH-UK
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ASCO herceptin trial updates for primary BC

http://www.nlm.nih.gov/medlineplus/n...ory_50099.html

The benefits seen at two years have at the very least held for four years.

Also, the peak of recurrences for her2 positive BC is within the first two years.
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Old 06-06-2007, 08:20 AM   #2
Hopeful
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Thanks for posting, Christine. I am a little confused about the ending of the article, which reads:

"Interestingly, Perez also found that estrogen-receptor-positive tumors experienced a 15 percent improvement, even though many physicians had believed these tumors did not respond well to Herceptin.

'That's going to be news to a lot of people,' Perez said."

I wasn't aware that there was a question about the efficacy of Herceptin in Her2+/ER+ patients, and don't know what the "15% improvement" refers to.
Does anyone know?

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Old 06-06-2007, 07:00 PM   #3
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People that are her2 positive and hormonal positive have a lower rate of relapse in the first few years after diagnosis than her2+ that are hormonal negative. Therefore, the benefit for the hormonal positives may be less as their risk of relapse is less, perhaps somewhere around 15%, if the article quote is correct.
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Old 06-06-2007, 07:39 PM   #4
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Robin,

I have not seen anywhere that the relative benefits of Herceptin were 52% for hormone neg, and only 15% for hormone pos. All the quotes state a relative 50% benefit across the board. That is why the 15% does not make sense to me. Could it be 15% absolute benefit? That seems to correlate better with the math (i.e., 85% vs 70%).

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Old 06-07-2007, 07:07 AM   #5
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I'm trying to present this lower response in the best light possible. Yes, according to the article link in this post, hormonal positives that were her2+ repsonded less to Herceptin than hormona negatives, probably due to the cancer having another pathway via the hormones to proliferate. I do think the 15% figure that the article gave was less than I would have suspected. Therefore, I would want to check this number before I bought into it. Also, remember that maybe hormonal positives repsond less to H. but hormonal positives do relapse less than hormonal negatives .
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Old 06-07-2007, 12:07 PM   #6
Lani
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Martine Piccart, head of HERA trials and Edith Perez, head of No American trials of

Herceptin both presented at evening symposia at San Antonio 2006 that the improvement in recurrence rates for her2+ bc by the addition of herceptin to chemotherapy were the same, whether the her2+ bc was ER+ or ER- according to the data as evaluated to that date.

I read the last sentence as saying there was some benefit found for her2-ER+ bc--which might be because some of these metastasize after becoming antihormonal resistant as her2+ bc. Perhaps the herceptin prevented that or treated that.

Am just speculating...this was my take on it...
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Old 06-07-2007, 12:11 PM   #7
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From Joe's post--this might explain things...a third possibility

ie, that the her2 testing was inaccurate, thus some her2-ER+ patients were found to benefit from herceptin...it seems her2 testing is plagued by both false negatives and false positives:


But one of the slides Perez screened at the annual meeting of the American Society of Clinical Oncology showed that some patients who were classified as HER2-negative got the same benefit as those who tested positive. Perez's data contained too few patients to be statistically significant, but another researcher was scheduled to present similar findings Tuesday in a bigger set of patients.

That caused a buzz among the cancer doctors gathered at McCormick Place, many of whom said the finding raised serious questions about their ability to offer patients the best possible treatment.

Dr. Kathy Albain, director of breast research at Loyola University Health System in Maywood, predicted the data would cause "mass confusion," adding, "It will give me pause to remeasure someone who is initially HER2-negative."

Perez also suggested it might make sense to retest anyone whose first test was negative, just in case it's a false result. "I'm worried about excluding patients who might benefit," she said.

Drug expensive, risky

But Dr. Dennis Slamon of UCLA, who is largely credited with developing Herceptin, noted that false-positive results are also problematic, because the drug costs about $3,000 a month and has sometimes-serious side-effects, including a heightened risk of heart failure.

Dr. Michael Press, a pathologist at the University of Southern California, said as many as one-third of positive antibody tests "could be false-positives."

Slamon called for a high-level task force to figure out how to reduce errors in testing for HER2. As a first step, he said, any negative tumor samples of women who got Herceptin in the clinical trials should be retested by independent, "blinded" pathologists to make sure they're true negatives.

Slamon said there have always been "technical challenges" to determining whether a patient is positive or negative for HER2. One study found that when five pathologists looked at the same slides, they disagreed on the diagnosis in half the cases. "This will bring it to a head," he said, "and that's a good thing."

Early errors found

Shortly after Herceptin was approved by the FDA in 1998, studies began showing that the lab tests to determine if breast-cancer patients should get the drug often yielded false results.

At first it was believed most of the bad results occurred when less-experienced, community laboratories processed the samples or used non-standard test kits. So researchers insisted the tests be performed in a central lab that has processed at least 100 HER2 tests a month for six months.

But Perez said Monday that some of the women who responded to Herceptin in her trial had received negative test results from the central pathology lab that was entrusted with overseeing all the samples.


http://m.trb.com/b/ss/tribglobal/1/...&hp=N&[AQE]
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Old 06-13-2007, 07:53 PM   #8
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Ladies, the hormone positive people do better in general due to tamoxifen/AI reducing their risk of recurrence by 40%. With chemo reducing 40%, the hormone therapy another 40%, the 15% added benefit of hercepting brings up the total benefit of tamoxifen+herceptin to about 55% -- essentially the same as the hormone negative ladies.
So, take a deep breath and relax!
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Old 06-14-2007, 01:50 AM   #9
Lani
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dilly

I think you have oversimplfied the matter because the true statistics have not been gathered/published. The decrease in recurrence for AIs/other antihormonals are for ALL BC patients. As we all know, if you take statistics for ALL BC patients they just don't hold for her2+ patients. Her2 has not been tested for that long, in that many patients and with enough exactitude to generate the kind of statistics needed it seems.

I have asked Charles Perou, who is one of the world experts on the molecular subtyping of breast cancer (look his articles up on PubMed) about
where her2+ER+ tumors fit into all this

He admits they still really don't know where the "her2+ER+s" should be classified, with most of them falling within the luminal B group (which is a hodgepodge of other tumors with quite diverse gene expression profiles)rather than in the "her2 group" (where the her2+ER- tumors lie)

Most have VERY different genes up- and down- regulated than most her2+ER- TUMORS and there is a great deal of diversity even within the her2+ er+ group.

The old statistics from Adjuvant online have not yet been adjusted to take into account our knowledge of the molecular subtyping. I will be hearing a lecture from the man who "invented" Adjuvant online within the next month in which he discusses just that.

Who would pay for all breast cancer tumors to have a gene expression profile( best done on fresh or freshfrozen tumor specimens) in order to subcategorize them to discover the natural history of each, recurrence rate of each, best treatment for each?

If Edwards were President or VP, I am sure the money would be found.

Were that to occur ie, with such a precedent, I am certain the fight against cancers OF ALL TYPES
would be greatly accelerated.
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Old 06-14-2007, 05:04 AM   #10
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Lani,

Wow, you got to speak with Dr. Perou - how cool! I read as many of his papers as I could find on line right after I was dx last year. Thanks very much for clarifying that the Her2+ ER+'s are classified as Luminal B. I have tried searching for hard stats on how AI's affect specifically Her2+ ER+'s, but, other than references that they are an improvement over Tamoxifen, I have found nothing more specific.

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Old 06-14-2007, 12:02 PM   #11
Christine MH-UK
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'Help Defeat Cancer' project tried to link genes, treatments and outcomes

Hi Lani,

What you are describing in terms of looking at large numbers of breast cancer markers, treatments used, and recurrence rates sounds like what the 'Help Defeat Cancer' project on the World Community Grid has been trying to do. As I recall they were analyzing microarrays of hundreds of thousands of samples and were hoping that findings could be used to match treatments to patients. Researchers at a medical school in New Jersey had developed the project and prepared all the samples. The computers just finished crunching the data from the project a short time ago, so there are no findings yet, but this is an active area of research.
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