Live 2005 SABC on the net now!!!!!!!!!!!!!

[RobinP]

Wow, I just watched the 2005 SABC live webcast with Dr. D. Slamon, discussing the trail results of BCIRG, and the speaker for the HERA discussing trail results. These webcasts were excellent presentations on the uses and risks of adjuvant herceptin.

I found it particularly interesting that in the HERA discussion, node negative her2+ er,pr+ subtypes only had a 9% risk of recurrence of bc in two year follow up. This risk was so low that the investigators will be watching this group in follow-up to determine if Herceptin is indicated in this subtype. On the other hand, node negative er, pr negative, her2+ subtype relapse risk was at an alarming 18%! The break down of risk for relaspe in 2 yr. f/u is as follows:

ER,PR Negative, her2+
Node Negative 18%
1-3 nodes 25%
greater 4 nodes 33%

ER,PR positive, her2+
Node Negative 10%
1-3 Nodes 12%
greater 4 nodes 33%


Dr. Slamon's presentation, was enlighting as well. He indicated that the cardiac risk for the AC-TH group was as high as 17% cardiac risk of over 10 percent presistent LONG LASTING damage to the heart. He said the heart loss was beyong 550 days; much longer lost than historically thought.He felt the AC-TH combination was only indicated if you test TOPOII positive where AC targets TOPOII and Herceptin targets her2+.Otherwise, AC combination with herceptin should be avoided due to CV risks.

This makes me wonder if the Finnish trail, who had no CV risk, has efficacy in the TOPOII subtype, in particular. Additionally, it looks like Herceptin AFTER adjuvant may be advantageous to herceptin commitant with AC as we know the HERA trail had much less CV risks of 0.5 percent severe CHF, 1.5% CHF and 7% one episode of decreased LVEF during infusion. Note, according to the HERA speaker, 95% of the adjuvant chemo in HERA was AC; however, this AC was not given with Herceptin as the BCIRG trial.

[AlaskaAngel]

I listened to a conference from Cancercare this week with Dr. Winer as one of the speakers. In response to a question about early stage HER2 positives who are stuck in limbo, he briefly mentioned the possibility of clinical trials this year. Did Dr. Slamon say anything about that?

A.A.

[RobinP]

Hi AA,

I listened to Dr. Salmon's live webcast and he did not mention anything about clinical trails for late Herceptin.

[Joe]

It is not that Herceptin would not be effective in late HER2 patients, but only that it had never been studied. When researchers apply to the FDA to do a clinical trial, they have to outline in great detail all of the inclusion/exclusion criteria. In the case of the adjuvant trials, I believe one of the exclusions were that the patient had to have completed their chemo within 6 months of the start of the trial. I understand that some of these applications exceeds 100 pages so it is an extremely detailed document.

After the completion of the trials, the drug companies can only "label" according to the trial results. Hence, although Herceptin is still only FDA approved for stage IV metastatic bc patients. Genentech will apply to the FDA in the first quarter of 2006 to "relabel" the drug to include earlier stage patients as a result of the recent trials.

Any oncologist is free to prescribe any FDA approved drug if he feels it will help his patients, even if they do not meet the criteria outlined according to the product's label. This is commonly called prescribing "off-label" .

If you are more than 6 months out from your initial chemo, I am sure that many oncologists would readily prescribe Herceptin. You may have to shop around.

Regards
Joe

[Joe]

I would suggest looking into Tykerb (Lapatinib) trials. These Phase III trials are being held widely across the US and many are for women who progressed with Herceptin.

Could you please provide the source of your reference to 20% of her2+ patients becoming negative once they metastasize. (I may have read you wrong, but I assumed you meant that their mets were negative for her2 whereas their primary was her2positive) I think you may have this wrong, as I have read that contrary to Estrogen receptor, where mets from ER positive patients may be ER negative and mets from her2negative patients that may be her2positive. that "once her2positive, always her2positive" ie, if primary her2positive than mets her2positive. This has to do with what was discussed at length during questions after talks at SABCS--whether the ER is present on breast cancer stem cells (or only on the progenitor cells) or not. It has been felt by Max Wicha and others that her2 is likely present on stem cells--thus the primary tumor may represent a quickly dividing/growing group of more differentiated progenitor cells where as the mets come from the previously dormant stem cells .

This has been important in a very interesting and frightening paper I found
on the prognostic significance of her2 positive isolated tumor cells in bone marrow (ie, they did cytokeratin AND her2neu double staining ) by IHC.

Will try to search for that article and post it for you

Lani

I saved this a while ago. I am out of my depth but I suppose it helps answer half of the question.

Interestingly the status of the eigth person referred to is not given.

It is clearly a highly significant issue for those potentially vulnerable.

RB



http://www.cancerlineuk.net/news/7910.aspx

ABSTRACT

Testing secondary tumours that have spread to various areas of the body for a protein called HER-2 may help identify the most effective treatment for some women with advanced breast cancer, results of an Israeli study suggest.
However, Dr Jamal Zidan, from the Sieff Government Hospital in Safed, and colleagues have found that not all secondary tumours have the same biological makeup as the original breast cancer, suggesting that some women with breast cancer that has spread to other areas of the body are not receiving the most effective treatment for their condition.
For the study, the researchers assessed HER-2 levels in the primary and secondary tumours of 58 women with advanced breast cancer.
They found that eight of the women had primary and secondary tumours that were biologically different. Of these eight women, seven had primary breast tumours that were negative for the HER-2 protein, while their secondary tumours were positive for the protein.
As a result, four of these women were treated with trastuzumab in addition to chemotherapy, and three responded to the treatment having initially failed to respond to chemotherapy alone.

[RobinP]

Here's the abstract from SABC on her2 status change.I would like to have seen this in a bigger cohort; however, I think similar findings have been found in other research that I have read.



[2019] Concordance of HER2 and hormone receptor expression in primary and recurrent breast cancer.

Wirk B, Geiger X, Hillman D, Perez EA. Mayo Clinic, Jacksonville, FL

Background: Determination of accurate HER2 and hormone receptor status is of primary importance in breast cancer treatment. Concordance of expression of these 2 prognostic and predictive factors between primary and recurrent tumors provide guidance related to the potential need to re-biopsy patients at the time of recurrence, or managing them based on the characteristics of the original tumor. Methods: Retrospective review of all medical records available of patients (pts) with recurrent breast cancer between 1997 and 2003 (160 cases total) at a single institution as to whether expression levels of HER2 by immunohistochemistry (IHC) using HercepTestTM or fluorescence in situ hybridization (FISH) using PathvysionTM as well as ER (estrogen receptor) and PR (progesterone receptor) by nuclear staining differ in the primary tumor and the asynchronous recurrent lesions. Results: Out of 160 cases, 39 pts (ages 41-85 years) had HER2 status available on the primary breast cancer and biopsies of the asynchronous recurrent breast cancer lesions. 8 (20.5%;95% CI 7.8-33.2%) pts had HER2 status conversion (table 1). 7 pts with HER2 status conversion had HER2 status determination by HercepTest and 1 patient had FISH. All pts with HER2 concordance had HercepTests. 14 (35.9%; 95% CI:20.8-51%) pts had ER/ PR status conversion from the primary breast cancer to the recurrent breast cancer (table 2). Of those pts with HER2 status conversion, the disease free interval (DFI) was 10 to 45 months. Of those with HER2 status concordance, the DFI was 9 months to 12 years. 7 of the 8 pts with HER2 status conversion had locoregional recurrence (with biopsies of the breast [4 pts], axillary lymph node [2 pts], chest wall [1 pt]) and 1 had distant recurrence (biopsy of the bone). 3 of 8 pts with HER2 status conversion had ER and PR status conversion (ie ER+ or PR+ status of the primary breast cancer and ER- PR- status of the asynchronous recurrent breast cancer). 4 of the 8 pts with HER2 status conversions received anthracycline based chemotherapy and tamoxifen; 1 of the 8 pts received tamoxifen alone; 3 of the 8 pts received chemotherapy alone and 6 of the 8 pts received radiation for their primary breast cancer. Conclusions: Changes in HER2 (20.5%) and hormone receptor expression (35.9%) were found between the primary and asynchronous recurrent breast cancer. Pts with recurrent breast cancer should have new biopsies performed to best determine whether therapy with trastuzumab and/or antiestrogen therapy is indicated. Only 39 of 160 recurrent breast cancers examined between 1997-2003 had biopsies of the recurrent lesions and data regarding the 2004 metastatic breast cancer cases are forthcoming.

Table 1. Number of patients Primary breast cancer HER2 Recurrent breast cancer HER2 4 HER2 2+ IHC HER2 0 IHC 1 HER2 3+ IHC HER2 1+ IHC 2 HER2 0 IHC HER2 3+ IHC 1 HER2 FISH amplification HER2 no FISH amplification



Table 2 Number of patients Primary breast cancer ER PR Recurrent breast cancer ER PR 7 ER+ or PR+ ER- PR- 2 ER- PR- ER+ PR+ 4 ER+ PR+ ER+ PR- 1 ER- PR- ER- PR+



Friday, December 9, 2005 7:00 AM

Poster Session II: Detection and Diagnosis: Diagnostic Pathology (7:00 AM-9:00 AM)

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[Christine MH-UK]

Both HERA and the Finnish trial had low cardiotoxicity. The anthracycline used in the Finnish trial was epirubicin (the E of FEC), sold under the trademarked name Ellence, and many of the women on HERA would have had FEC, since epirubicin is more common that adriamycin in most of Europe. M.D. Anderson made news at ASCO 2004 by giving women FEC+herceptin AT THE SAME TIME to patients and getting a really good response rate and there weren't heart problems, whereas AC at the same time as herceptin caused heart failure in 25% of patients with secondaries in a separate trial, which is why it isn't done. Perhaps this is something that the oncologists should consider when designing future trials. I don't think that FEC and AC have ever been run head-to-head.

Topo IIa amplification (or deletion!) seems predict FEC sensitivity, whereas HER2 does not (as I know all too well :-(
http://www.ncbi.nlm.nih.gov/entrez/q...514&query_hl=3

[RobinP]

Epirubicin is the sister cousin to AC but has less cardiac side effects so it makes sense to use it with Herceptin rather than AC, especially for those who have TOPOII. Thanks for pointing that out; oncologist should consider that mix, FEC+herceptin for TOPOII and her2 expressers.

[RhondaH]

I think my doc was planning on IF I needed Herceptin.

Rhonda

I was at SABCS and went to all the poster sessions, but I missed that one.

If you have any other sources of similar information re her2+ (particularly FISH+) recurring as her2-, I would appreciate your passing it on!

Thanks again,
Lani

[RobinP]

The 65 % for greater 4 nodes for er,pr+ should be 55% when I doubled check this for you. Also, just go to the san antonia breast cancer site and click live webcast 2005 for the lecture

[sassy]

Robin,

Do you have a link because I can't find it on the site--or maybe I'm going to the wrong site.

Thanks for the help,

Sassy
________
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[RobinP]

http://www.sabcs.org/SymposiumOnline/index.asp#webcast

[sassy]

Thanks, Robin, I did find the webcast, and it appears rate of recurrence for four or more positive nodes for both hormone negative and hormone positive stands at 33%. Close to what my onc has been telling me. That is very interesting considering the difference of percentage in the node negative and 1 to 4 node positive hormonal comparison.


Was glad to see the 4 or more positive was at 33% rather than 55%! I feel 22% better!


Sassy
________
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[RobinP]

Really? Maybe I need spectacles, I thought it was 55% on the bar graph. Anyway, I hope you are right about 33% for your sake.

[Christine MH-UK]

And I bought a new set of eyeglasses recently. You can also tell by the relative size of the bars.

I find it interesting that hormone receptor status doesn't affect outcome when loads of nodes (4+) are involved. I don't think anyone would have expected that.

[sassy]

That is not what you would expect looking at the other numbers. Looking at the original number Robin put up, I was expecting about 26 or 27%. Seeing that node negative was actually 33%, would have thought node positive would come in around 18%, even though my onc has been telling me about 30%. I wish it had been!

Sassy
________
Park Royal 2 Condominium

[Alice]

How do I find SABC on the net.I'm not good at finding things and would very much like to see this.

Thanks, Alice