HER2 and Breast Cancer Recurrence

M. D. Anderson Cancer Center
Cancer Newsline Audio Podcast Series
Date: December 15, 2008
Duration: 0 / 13:04

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Edward Kim, M.D:

Welcome to Cancer Newsline, a weekly podcast series from The University of Texas M. D. Anderson Cancer Center. Cancer Newsline helps you stay current with all the news on cancer research, diagnosis, treatment and prevention – providing the latest information on reducing your family’s cancer risk. I’m your host, Dr. Edward Kim, assistant professor in M. D. Anderson’s Department of Thoracic Head and Neck Medical Oncology.

Today we’ll talk to Dr. Ana Gonzalez-Angulo, assistant professor in M. D. Anderson’s Breast Medical Oncology and Systems Biology. Groundbreaking study result presented just this week at the San Antonio Breast Cancer Symposium suggest that women with the earliest stage of breast cancer whose tumors are 1 cm or smaller and express an aggressive protein called HER2 are at a significant risk of recurrence of their disease compared to those with early stage disease who do not express the aggressive protein. This finding is the first large study to analyze this cohort and represents a shift in the way women with early stage HER2 positive breast cancer should be assessed for risk and possible treatment.

Thank you very much Dr. Gonzalez-Angulo for joining us today.

Ana Gonzalez-Angulo, M.D.:

Thank you for having me.

Dr. Kim:

Can you offer our listeners in lay terms a little history about the HER2 protein and what Herceptin has offered women with HER2 positive breast cancer?

Dr. Gonzalez-Angulo:

Sure. So, a few years ago a researcher from University of California Los Angeles named Dennis Slayman started to study this protein that is called HER2 and he showed that there was an important correlation of the levels of HER2 and the prognosis of breast cancer. In fact, the patients that had HER2 positive breast cancer were the patients that had the worst prognosis. Further, he actually joined with a pharmaceutical company to build this new targeted therapy called Herceptin, which is a monoclonal antibody, a type of immunotherapy that looks for that protein. In particular, when he is expressing the cancers and by finding the protein helps destroy the cancer cells.

This new medication was studied in patients that had advanced breast cancer and was one of the first medications that showed that the survival of patients with advanced breast cancer was improved by using it. Further, in 2005 four large clinical trials done in the United States and in Europe demonstrated that by using this medication in combination with chemotherapy, patients that have early HER2 positive breast cancer had at least half of the risk of recurrence that they used to have before this medication was available.

Dr. Kim:

Now for those patients who aren’t familiar what Herceptin is or a targeted agent, what type of impact has a drug like Herceptin really meant in the landscape of patients who are treated with different cytotoxic chemotherapy or hormonal therapies.

Dr. Gonzalez-Angulo:

Well, I think it’s a breakpoint for all of us because now we are tying to personalize a little bit more how we are giving treatments to our patients. Our goal is that one day we can avoid as much toxicities and use more of these targeted agents to focus in the biology of the tumor instead of giving just the same chemotherapy to everybody. Currently we know that, at least for patients with early breast cancer, we should combine with chemotherapy because apparently the results are a little better, so both medications – the chemotherapy and the Herceptin help each other. But, it may come to a point that we can select the patients particularly for certain types of cancer which we can use only targeted therapy and minimize toxicity as much as possible.

Zwelling:

And what are the primary toxicities associated with Herceptin?

Dr. Gonzalez-Angulo:

So, Herceptin is actually a very well tolerated drug. The main side effects or the most common side effects patients can have are infusion reactions since this is an antibody. They can have some chills or fever during the infusion. And then, the long term side effect we have seen that is reversible is actually cardio-toxicity. What it means is that it can make the heart weak, so a patient can end up with congestive heart failure. That is the reason because it is important to select a proper chemotherapy that we want to combine Herceptin with, as well as evaluate before they are given Herceptin and during the Herceptin therapy for cardiac events.

Dr. Kim:

So why did you decide to look at this study specifically at early stage breast cancer patients with tumors 1 cm or smaller? I understand that this study represents a real current debate within breast cancer clinical practices.

Dr. Gonzalez-Angulo:

Correct. So, basically in 2005, the large adjuvant studies using Herceptin were presented. And what we saw was that there was an extreme benefit from the use of Herceptin in these patients. We saw that the risk of recurrence was cut by about 50 percent. But most of the studies were in patients that had positive lymph nodes – so fairly advanced disease - and in two studies one-third of the patients had negative lymph nodes. What happened later was that only one clinical trial had a few patients that had these small tumors, but we did not know what the risk was for patients that have these small tumors to develop recurrences, to have metastasis. And, everyday we see, or every week we see these type of patients in clinic and we just don’t have enough data to support or recommend either X or Y treatment or not recommend any treatment. So that was kind of the idea of looking into it.

Dr. Kim:

So if I’m a woman whose been newly diagnosed with breast cancer and my tumor is found to be smaller than 1 cm and it’s found to be HER2 positive, what current guidelines would someone like yourself explain to me about that?

Dr. Gonzalez-Angulo:

So the main guidelines that we use all over the United States are the NCCN guidelines and for these particular size of tumors that are HER2 positive, the guidelines say that if the tumor measures from 6 mm to 10 mm, we should discuss adjuvant therapy to the patients. It doesn’t’ say which type of therapy, what type of chemotherapy, we should combine with Herceptin. It doesn’t say much. There are no current recommendations for patients that have 5 mm or smaller. We keep seeing more and more of these patients since we are diagnosing breast cancer earlier and earlier.

Dr. Kim:

Now your study is quite impressive in the fact that there is much research done in breast cancer and it’s hard to really find the changes in treatment guidelines. Can you provide just an overview of your study – what the goal was and what are the findings?

Dr. Gonzalez-Angulo:

What we did is assemble a cohort of patients that were treated at M. D. Anderson that had tumors that were 1 cm or less. We had 965 patients. The important characteristics of these patients is that they did not receive any chemotherapy, nor any Herceptin, so we could really tell what was the difference what was the true risk of having a HER2 positive small tumor compared to a HER2 negative tumor. We looked into that and we saw the patients that had HER2 positive small breast cancers had a 5 year risk of recurrence or about 23 percent compared to the patients that had HER2 negative breast cancer had a 5 year risk of recurrence of less than 10 percent. It was about 6 or 7 percent. This was a very significant difference. Then, what we did is we assembled a second set of data from two collaborative institutions in Europe of 350 patients and repeat the analysis and saw that the data was reproducible, meaning that we saw exactly the same findings. So, with a little bit more certainty we can say these patients are a high risk of recurrence and we should either discuss therapy with them or at least start contemplating what clinical trials we should design to treat them.

Dr. Kim:

So the impact of this data, how are physicians going to apply this knowledge? Will they do it immediately? Personally I would think that physicians will need to really asses how they care for these patients and perhaps offer Herceptin in the post operative setting.

Dr. Gonzalez-Angulo:

Correct. So I think that the main findings of this study allowed us to be a little more confident when we talk to our patients and tell them ok, although your tumor is small, the risk is high and we should at least consider the possibility of giving you treatment, and that treatment should definitely include HER2 therapy with Herceptin.

Dr. Kim:

Do you have plans for follow up research, or plans for a specific clinical trial? Are there ways to incorporate these patients into current clinical trials?

Dr. Gonzalez-Angulo:

Well, we have a couple of plans. One is we are trying to look into the NCCN database to try to confirm one more time our results. This is a very important database that encompasses centers from all the United States. So it will be interesting to look at them, if we have enough follow up for those patients.

The second part is how can we incorporate these patients in clinical trials? And I think that there are several clinical trials ongoing for HER2 positive patients, so the most practical way of doing this is make these clinical trials available for patients with small tumors.

The other way, or maybe the ideal way will be to study a clinical trial in which patients with small tumors are randomized to two groups and one group will receive Herceptin alone and the second group will receive chemotherapy in combination with Herceptin. We may need a third group that have to be controlled, but at this point, having this risk of recurrence I doubt that we could do it that way.

Dr. Kim:

I think that’s potentially very exciting to be able to treat patients with a single targeted agent, especially a very specific population.

Dr. Gonzalez-Angulo:

Yes, as we discussed before, I think it’s interesting that now we are looking more at the biology of the tumors more than the physical characteristics like size and how many lymph nodes are involved. I think that sometimes patients that have smaller tumors may have worse prognosis than patients that have larger tumors and if we focus on the biology of the tumor and these new targeted therapies that are directed to the specific biology of the tumor, we can get better results for patients with less toxicities.

Dr. Kim:

Great! Well, thank you very much for talking to us about your study. Any closing thoughts that you would like to share? Anything that we have not covered, and especially most importantly, what is the take home message you would send to our listeners out there who are going to listen to this podcast?

Dr. Gonzalez-Angulo:

I think that there are two messages. One, it’s very important for a patient as well as a doctor to know the complete information about a tumor including all these biological characteristics, not only the size and the presence of positive lymph nodes. And, for the physicians it is important that they have clinical trials available for patients so they can participate and help us confirm the findings in the prospective way.

And the other thing is, if there are no clinical trials available, at least we should be able to discuss these finding with patients and offer them therapy, since we think that therapy will benefit them.

Dr. Kim:

And if you are a patient now and you’ve found your study online or on our webcast series, what do they need to do when they approach their doctors now with newly diagnosed breast cancer?

Dr. Gonzalez-Angulo:

I think that they should just show them the data and discuss with the doctor that if they have this small tumor that is aggressive at least they should be considered for therapy.

Dr. Kim:

Well thank you dr. Gonzalez-Angulo. If you have any question about anything you have heard today on Cancer Newsline, contact askmdanderson at 1-877-MDA-6789, or online at www.mdanderson.org/ask.

Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.

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