Issues with reliability in HER2 testing and avastin for metastatic breast cancer

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Published: 19 Jan 2011
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Dr Edith Perez – Mayo Clinic, Florida, USA
Dr Perez talks to ecancertv at the 2010 San Antonio Breast Cancer Symposium about a debate she took part in on the use of Avastin (Bevacizumab) for metastatic breast cancer and also her recent analysis of HER2 breast cancer tests, revealing issues with reliability. Results for testing breast tumours for HER2 proteins and genes are most often straightforward when one piece of tumour is analyzed. However tumours can be diverse and Dr Perez’s research found that HER2 results can vary in up to 10 percent of patients when several tumour blocks are analysed. This could have impact in the clinic.

2010 San Antonio Breast Cancer Symposium, 8-12th December, USA


Interview with Dr Edith Perez (Mayo Clinic, Florida, USA)



We feel that proper identification of patients eligible to receive the HER2 therapy is extremely important. We’ve been working on this for several years and we are presenting really very important data at the San Antonio Breast meeting. The new data relate to a very large ‘HER2 pathological round robin’ project. Specifically, what we set out to investigate was to determine whether there could be concordance amongst expert pathologists related to the results of HER2 testing. Additionally, we sought to figure out whether there was heterogeneity in the breast cancer. By that what I mean is that some portions of the tumour could be positive; some other portions of the tumour could be negative. And we also tried to determine whether there were true patients with HER2 negative breast cancer who had been enrolled in the adjuvant Trastuzumab trials that may have derived a benefit to Trastuzumab.


So we had a multi-prong approach to our trial and the results were very interesting. First we found out that amongst the pathologists there was similar concordance or similar discordance when they evaluated the protein or the gene. In other words, there was an 8% discordance between the expert pathologists in the results of the IHC or the FISH. So you might wonder why is that important? Well we dispelled the notion that some people had had that FISH was going to be a more reliable test for HER2 testing.


We also found that there was a 5-10% range of tumour heterogeneity for HER2, which means that in about 5-10% of the breast cancer cases, there were portions of the tumours that were HER2 positive and others were HER2 negative. This is very important because in practise we at this time only test one portion of the tumour to determine whether the patient should receive therapy or not with Trastuzumab. And now this calls into question that practice. We now think that decision should consider testing a second portion of the tumour if the first test is negative.


Two tests every time?


That is right – two tests and in some cases it may be important to test immunohistochemistry on FISH and then, if negative, to consider testing another portion of the tumour with those tests.


You were involved in a debate at SABCS 2010 about the use of Avastin?


Avastin, or Bevacizumab, is a fascinating drug; there is a lot of science behind the development of Avastin. We know that there is a major discussion on-going, the level of the FDA foreign drug administration related to whether this drug should remain on the market for patients with metastatic breast cancer and that decision is expected next week.


There were no new data of Avastin in the metastatic setting at this San Antonio meeting that were significant, but there were some very interesting data presented in the neo-adjuvant setting in a trial led by the German co-operative groups. In that trial they demonstrated that at least utilising Avastin concurrently with chemotherapy for a few months before surgery did not appear to enhance what we call the pathological complete response or eradication of the tumour except in one setting and that was in patients with triple negative breast cancer. In that subset of patients there was a 40% improvement in eradication of the tumour when the Bevacizumab was added to the chemotherapy. So I think it’s going to be a very important story to follow.