European Breast Cancer Conference, Vienna, March 2012

Managing HER2 overexpression in breast cancer

Professor Michael Untch – Helios Clinic, Berlin, Germany

Today we have a meeting where we present cases of breast cancer patients with a special type of tumour which is HER2 over-expressing tumours. Now usually these are very aggressive tumours but fortunately today we have different additional modern types of therapy which can help the patients.

We have trastuzumab which is an antibody against HER2, we have lapatinib. Both drugs are approved for the treatment of metastatic breast cancer patients with HER2 over-expression; trastuzumab, in addition, is approved for the treatment of adjuvant breast cancer patients and in the near future we will hear more about the combination of these two drugs and also a new type of drug which is pertuzumab, it’s a dual antibody, and also receptor tyrosine kinase inhibitors which are going to be approved in breast cancer patients.

What have you found when treatment is given before surgery?

We have the experience that in the neoadjuvant setting, so if the therapy is given before surgery, the efficacy of the treatment is very high, we can have pathological complete responses in about 50% of the patients which means that the tumour is completely eradicated from the breast and from the lymph nodes. And we have experience of more than eight years of follow up in breast cancer patients with this type of tumour and we can predict with the response of neoadjuvant treatment quite well the outcome of these patients. So, in summary, in HER2 positive disease one possible standard of therapy is neoadjuvant treatment with a combination of chemotherapy and HER2 blocking agents.

Is this currently a standard treatment?

Because we have the results of meta-analysis from the German neoadjuvant trials and we have a follow-up of these patients and we have large published trials in major journals and in the German national guideline, this is a standard treatment, so neoadjuvant chemotherapy with the addition of anti-HER2 agents.

What are the goals for advancing treatment?

I think that the most important message for the future will be that we have two types of knowledge, which are coming up from the neoadjuvant trials which we have done worldwide but especially from the German trials. Number one, in those patients who have a pathological complete response, meaning the tumour in the breast and in the lymph nodes eradicated, probably these patients do not need an additional treatment after those six months of treatment with chemotherapy and targeted so therefore we have to do additional trials for these patients. But especially in those patients who do not have a pathologic complete response, and these are those other, about 50% with the addition of anti-HER2 treatment, we have to look for new targeted agents after the neoadjuvant treatment. So we do kind of a selection – first, we know that 50% of the patients have a complete response, for those patients we could stop treatment. And for those other 50% of the patients who do not have a complete response we need additional post-neoadjuvant treatments and we are about to start these kind of trials with new agents like T-DM1.

What potential does T-DM1 have for these cases?

T-DM1 is a very intelligent drug because it links to an antibody, a very effective and very toxic molecule and this molecule is so toxic that it cannot be used as a usual chemotherapy. But in combination of this, I call it trionic horse, bound to an antibody, the drug combination is extremely effective and we have seen, in my own experience from trials in patients with metastatic breast cancer, that T-DM1 works even in patients who are pre-treated with trastuzumab or lapatinib. So of course we want to move this drug much further on in the treatment of breast cancer patients like in adjuvant or neoadjuvant trials.

Are there any clinical trials currently underway?

We have trials which are underway with this type of drug which is T-DM1 and probably we will have an approval in the year 2012 in patients with metastatic disease who are previously treated with trastuzumab and other HER2 agents. We have a very exciting year or decade in front of us, and especially for our breast cancer patients the message is that we have a lot of good drugs already on the market and more to come.