Clinical trial - Herceptin w/ chemo for HER2-low

KCandJsMom · February 2011

New here and looking for some advice from Herceptin users. I start chemo next week and.have been asked to participate in a nationwide clinical trial involving early stage (I am stage III - is that early???) HER2 - low patients to learn if adding a targeted therapy, Herceptin, to standard treatment with chemotherapy will prevent brest cancer from returning. Seems that in some HER2 positive trials, the breast cancers actually turned out to be HER-low but after reviewing the data, they found the Herceptin seemed to have benefit in keeping the cancer for returning even when the HER2 levels were in the normal range. Thus this trial.

If I go for it, there is only 50% chance I will get the herceptin meds, which would be in combo with docetaxel and cyclophoshamide (AC) otherwise I will be in the group receiving the conventional chemo treatment of doxorubicin and cyclophosphamide(AC) for 4 cycles followed by several cycles of Paclitaxel.

Originally they diagnosed me as HER2-positive (80-85%) so I was already expecting to take herceptian. They re-ran the tests after removing my tumer and found that I am actually HER2-low (15-20%). I'm 44, have a 5 and 8 year old, and want to be as aggressive in my treatment as possible as I don't want to put my family through this again!!!! But after looking at the SE, I wonder if I am needlessly adding additional stress to my heart, lungs, and body? This is a NSABPstudy, Phase 3. Was not sure where to post this, but figured you herceptin users might be the best place to start. Thanks for any advice.

orange1 · February 2011

If you were originally Her2+ you should be getting Herceptin. Period. You should not have to be in a clinical trial to get it. Once tested positive, you should not have been retested unless there was a known error in your original test.

You are correct that an analysis of a trial (I can't remember which, I'll look it up and post later) showed a very significant reduction in recurrence in patients that had tumors that ever tested positive for Her 2, regardless of test method and regardless of degree of positivity.

You need to tell your onc you want herceptin and ask him why he/she retested your tumor - to fill up his clinical trial??

orange1 · February 2011

Here is what I was referring to...

In this study - all classes of tumors that showed evidence of Her positivity (IHC 1+, 2+ 3+ and FISH+) benefited significantly from Herceptin, including tumors that scored IHC 1+ or 2+ and did notsubsequently test positive by FISH testing. From Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post Meeting Edition). Vol 25, No 18S (June 20 Supplement), 2007: 511AbstractBenefit from adjuvant trastuzumab may not be confined to patients with IHC 3+ and/or FISH-positive tumors: Central testing results from NSABP B-31S. Pal, C. Kim...others511Background: Trastuzumab is a humanized monoclonal antibody targeted to HER2 protein and currently indicated for Her2 positive breast cancer defined by overexpression of Her2 protein (3+ IHC staining by HercepTest) or Her2 gene amplification (Her2/CEP17 ratio over 2 by PathVysion FISH assay). These criteria were determined for advanced disease but have not been formally tested in the adjuvant setting. We examined these tests' ability to predict benefit from adjuvant trastuzumab in NSABP B-31. METHODS: All available tumor tissue blocks from the B-31 trial were sujected to HercepTest and PathVysion assay as defined in the B-31 protocol. Formal statistical test of interaction between HER2 levels measured by these two tests and benefit from trastuzumab was performed. RESULTS: 207 or 1795 cases (11.5%) showed gene amplificiation as as determined by PathVysion, and 255 of 1662 (15.3%) showed overepression as determined by HercepTest. 161 of 1662 (9.7%) had neither gene amplificiation nor overexpression There was a consistent benefit from trastuzumab in every subset defined by IHC or FISH. No statistical interaction was found between DFS benefit from trastuzumab and level of protein (p = 0.26) or Her 2 gene copy number (p= 0.60). Benefit was observed in patients with tumors that were negative for FISH and had less than 3+ staining intensity on IHC by HercepTest (RR= 0.36, p = 0.32). CONCLUSION: Current definition of HER2 overexpression/gene amplificiation based on data from adjvanced disease may need to modified for the adjuvant setting.In all categories of Her2+, regardless of degree or how measured, relative risk with Herceptin was less than half of what it was without. And all results were highly statistically significant, meaning results were likely not due to random chance.

KCandJsMom · February 2011

Thanks for your responses!

\First test showiing I was HER2 positive was WRONG. I am HER2 low.

When the oncologist initially reviewed results of my core biopsy she was immediately suspicious that some tissues had been switched. Something inconsistent with the Estrogen being positive, Progesterone being negative, and the HER2 showing - strongly positive (I think). She was going to have the lab back rack on my sample but since I went in 5 days later for the mastectomy, she just re-ran the test with the tumor they knew was mine. When she gave me my ACTUAL results today, she confessed that a similar mix up had happened recently with another patient and this lab, which is why she had to have the test re-run. I am HER2 low.

Trying to figure out if herceptin, which seems so promising with HER2 positive patients, is worth the small heart, lung etc risks I run by adding it to my treatment? I really got the feeling my dr felt like this may be a new standard of treatment in the future. And I am all about being aggressive to prevent re-occurrence. But I don't want to invite any problems, either.

orange1 · February 2011

I am still not understand why Her2 low is not considered Her2+. What does your path report say?

Based on the article above, it seems as though Herceptin could significantly reduce your risk regardless of weather you are Her 2 low or Her2+. I would try to get it anyway I could.

lago · February 2011

I was concerned about long term stress on my heart for Herceptin too. So far no issues. I have finished 6 tx of chemo (Taxotere, Carboplatin, Herceptin) and now just doing Herceptin only every 3 weeks.

Typically with Herceptin if you do experience heart issues they will stop or at least have you skip a treatment till your MUGA is normal. Most of the time heart related issues with Herceptin are reversed once you stop taking the drug as long as it is stopped before it creates damage.

Some chemos in combination with herceptin can make you more susceptible to heart issues. You need to discuss this with your onc. These may not be so easily reversed but can be successfully treated with meds.

This is a very personal decision. If I felt that there was a chance that it could help my survival I would do it. If you look at the stats for heart issues it really isn't that high. Also it can be treated if for some reason you fall into that risk. I rather take heart meds than treatment for advanced stage cancer. Odds are you will live longer with the heart issue.

jteach · February 2011

hi KCand Jsmom,

I understand. I was originally suppose to be in the Avastin trial, as I was told by my breast surgeon and onc that I was triple negative. The paperwork was submitted and the powers that be bounced me from the trial. Why? Because my pathology showed a 10% her2 positive in some areas.

So a year of Herceptin was offered to me. I replied that the 90% negative would be much better served with Avastin. I did not qualify though.

So I figured that, even with the risk for only 10% positive, it was a 10% better chance of fighting the cancer. I've finished the Herceptin with no side effects. Easy peasy. The easiest thing I've had to endure so far. I know there are risks, but so far, so good.

Best of luck! Janice

Clinical trial - Herceptin w/ chemo for HER2-low

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