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HER2-Positive Breast Cancer

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“We talk about breast cancer and other forms of cancer often here on Sound Medicine. And we can sometimes get into the weeds in discussing different genes and treatments and whatnot. So we thought we’d take a step back now and dig a little deeper into one particularly common form of breast cancer, and how treatments for it have really been transformed in the past decade. Out of an estimated 200 thousand cases of breast cancer each year, every one in five falls into the category of “HER2” cancer… Joining me to discuss what that means and how it’s treated is Dr. Eric Winer. Dr. Winer is a professor of medicine at Harvard Medical School, and director of the breast oncology center at the Dana Farber Institute in Boston.”

Dr. Winer: HER2 is a gene. It’s a gene that makes a protein, and when a breast cancer is what is called HER2-positive, there are typically too many copies of the gene in the nucleus cell and too much HER2 protein sitting on the surface of the cell. That protein has the ability to make the cell spread more, grow more, be more resistant to certain therapies. This is an area where there have been completely dramatic changes over the last 15 years. It’s important to point out that HER2-positive breast cancer only accounts probably about 20 percent of all breast cancer, but we are still talking about 40,000 cases a year in the United States, so this is more common than many other kinds of cancers and many other health problems. Prior to the year 2000, HER-2 positive breast cancer was considered one of the worst types of breast cancer. It was responsible for, relatively speaking, more deaths than other types of breast cancer. What’s changed is that there have been therapies that have been developed that very specifically interact with HER-2 and take it out of commission.

Lewis: So we’ve heard of Herceptin. Is that the big one? Or are there other ones that are very affective against HER2?

Dr. Winer: Herceptin is the prototype. It was the first. In truth, when Herceptin first became available, I think many people, and I'm one of those many people, would not have imagined that it would have such a profound effect on the course of HER2-positive breast cancer. When it was first approved, it was approved for women who had advanced HER2-positive breast cancer, so breast cancer that had spread outside of the breast, to places like the liver and the lungs. Since that time, what has happened is we’ve seen the widespread use of Herceptin as a result of results from clinical trials; the widespread use of Herceptin in women with earlier stage breast cancer to prevent a recurrence; and then, over the last several years, there have been three drugs developed, which also, very specifically interact with HER2. And these are three of more that are yet to come.  One of them still plays a relatively limited role. And that’s the drug that is called Lapatinib. Two drugs:  once called Pertuzamab and one called TDM1 have been both shown in women with breast cancer to very clearly control the breast cancer and have also been shown to improve survival.

Lewis: One last question about Herceptin. How much of an increase in survival rates? Or how affective has it really been on both maybe the quality of life and the survival among the women who are HER2-positive?

Dr. Winer: Quantifying survival is pretty tough. The reason it’s tough is because we can quote you numbers from a specific clinical trial or we can quote for a patient. But as it’s turned out that it’s not just giving Herceptin once as part of an initial therapy that is important, it turns out that it’s giving anti-HER2 therapy for the duration of someone’s illness. And it’s really hard to know the magnitude of the survival benefit doing that compared to not using it…  Women with HER-2 positive breast cancer today (and this is advanced HER2-positive breast cancer; there are many, many women with HER2-positive breast cancer who are cured and I’ll speak more about that in just a second), but for women who have advanced HER-2 positive breast cancer, there are women living with this for five years, and eight years, and ten years, and this was almost unheard of in the past. And for women with early stage HER-2 positive breast cancer, so breast cancer that can be removed surgically and treated with the intent of curing a patient, we’ve cut in the half the number of people who have recurrences with Herceptin.

Lewis: TDM1 and the other drugs that are currently available that are showing great promise for women with HER-2 positive breast cancer, are they used in conjunction with Herceptin?

Dr. Winer: So the drug Pertuzamab, is given in conjunction with Herceptin.. TDM1 Is Herceptin. TDM1 is a very complicated drug, but in many ways, the kind of drug we hope to develop more and more of in the future. TDM1 is Herceptin linked to a tiny dose of chemotherapy. It works in two ways: One, it works just like Herceptin. The Herceptin part of TDM1 Attaches to the Her2 positive breast cancer cell and it essentially negates the effect of HER1.. But then it also acts essentially as a delivery truck, so it’s a Trojan horse. It comes to the cell, it drops off its payload (the payload being the DM1, which is a tiny dose of chemotherapy), that DM1 is internalized into the cancer cell, it destroys the cancer cell, and virtually no DM1 is released into the systemic circulation, and the result is a drug that is very, very affective, and at the same time, unbelievably very well tolerated. It’s not entirely without side effects, but compared to standard chemo therapy, the side effects are far, far reduced and that’s now been shown in several clinical trials.

Lewis: Of the drugs that are being developed, which ones are you most excited about, when it comes to HER-2 positive breast cancer?

Dr. Winer: I think TDM1 is clearly a drug that is going to go a longer way in probably a very long way. We need the result of trials before we know how far it will go for the treatment of some patients..

Lewis:  When we think of get rid of chemo therapy and we’re talking about TDM1, I’m thinking how do you do that? What does that look like?

Dr. Winer: TDM1 essentially is chemo therapy. But it’s chemo therapy that doesn’t feel like chemo therapy because it’s this tiny dose that goes directly to the cancer cell.

Lewis: Is it an IV? Is it a pill?

Dr. Winer: It is an IV. When I talk about getting rid of chemo therapy, I’m talking about getting rid of drugs that make you lose your hair, getting rid of drugs that make your blood count low and put you at risk for infection, getting rid of drugs that just make you feel badly. What we would all like to see is the development of drugs that people can take and simply don’t have a major impact on their quality of life. Herceptin is a drug like that. The down side of getting Herceptin is that you have to go in every three weeks and you have to get the drug. But apart from that, it has relatively few side effects. Almost none. TDM1 isn’t quiet that easy, but it’s pretty close.  And the hope is that a woman with newly diagnosed breast cancer at some point in the future (HER2-positive breast cancer), might be able to have surgery done, and then instead of receiving chemo therapy could get something as simple as TDM1 by itself, might not have to experience hair loss and the other side effects. And less people think that I or anyone thinks that this is enough or this will take us where we really want to go. Of course, ultimately where we want to go is treatments that are easier than this. Treatment that don’t involve surgery, that don’t involved intravenous therapy. And finally the hope is that we eliminate breast cancer. But that’s going to take that much longer. 

Dr. Eric Winer is a professor of medicine at Harvard Medical School. He's also the director of the Breast Oncology Center at the Dana Farber Institute in Boston.