HER2-Positive Breast Cancer Recurrence

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Jamie DePolo: Hello, everyone, and welcome to the Breastcancer.org podcast. My name is Jamie DePolo, the senior editor at Breastcancer.org. Our guest today is Dr. Marleen Meyers, who is a medical oncologist and clinical assistant professor of medicine at NYU Langone. She also serves as director of the Perlmutter Cancer Center Survivorship Program. She received her medical degree from the NYU School of Medicine and has been in practice for more than 20 years. In today’s podcast, we’re going to discuss HER2-positive breast cancer and its recurrence risk. Dr. Meyers, welcome to the podcast.

Marleen Meyers: Thank you so much for having me.

Jamie DePolo: Just in case anyone isn’t aware, let’s start out, if you could explain HER2-positive breast cancer: what it is and how it ranks in terms of aggressiveness compared to other types of breast cancer.

Marleen Meyers: Of course. So, when we think of breast cancer and you think of a breast cancer cell, as clinicians, when we’re looking at the best way to treat people, we look at three proteins on a cancer cell among, of course, many other things. And those three proteins on a breast cancer cell that we specifically look at include two that are hormone receptors, estrogen and progesterone, and one that is called the HER2, which stands for human epidermal receptor.

And typically, when this receptor is amplified or we see that the receptor is there, it generally imparts a more aggressive type of tumor that makes a lot of people, of course, very anxious when they first hear about it. And back in the olden days, so to speak, before we had good therapy for these kinds of tumors, HER2-positive breast cancers, as they’re called, would have been ranked among the more aggressive breast cancers. Probably a bit less aggressive than triple-negative, but certainly more aggressive than estrogen- and progesterone-receptor-positive breast cancers. And what has changed over the years is not the fact that those breast cancers that are HER2-positive have become any less aggressive, it’s just that our treatments for these cancers have become significantly better.

Jamie DePolo: Okay. And that kind of leads into my next question. So, I know that there are treatments, Herceptin and Perjeta, specifically for HER2-positive breast cancer. So, it sounds like those treatments have perhaps, as you said, not made it any less aggressive, but made it perhaps more treatable.

Marleen Meyers: Yes. And certainly, in my professional lifetime over many years the discovery of HER2 blockers is really one of the most wonderful things that I’ve seen in breast cancer treatment. Because it has taken what is notably a more aggressive cancer and has greatly improved how well chemotherapy works as well as overall survival. And we’ve seen just dramatic changes in people in all settings, in all stages of breast cancer, by using HER2 blockers.

Jamie DePolo: Every person’s risk of breast cancer recurrence is unique, we know that. What factors do you consider when you’re estimating someone’s risk of recurrence?

Marleen Meyers: There are many factors that need to be looked at, and the most important thing to realize is that every single breast cancer is truly unique. So even when we look at the literature and we look at studies and we look at statistics, one has to keep in mind that no individual person is the same as the statistic. So, when we talk to our patients about breast cancer and risk of recurrence, often it’s very frightening to go online or to read about the risk of recurrence. But you have to take a step back and say, “My cancer is individual and unique.”

And some of the things as oncologists that we look at is we look at these three biomarkers as they’re called, the estrogen, progesterone, and HER2. We look at the stage of the tumor, which includes the size of the cancer as well as lymph node involvement: how many lymph nodes, how much are they involved? We look at the grade of the tumor, which means how aggressive do the cells look under the microscope? And in recent years we’ve gotten much more sophisticated in looking at the true molecular biology of the tumor and really parsing out which cancers are likely to be more aggressive and should be treated more aggressively, and which cancers are less aggressive.

And one big trend that we’ve been seeing in oncology in recent years is the less-is-more trend. And we’ve really tried to get away both in chemotherapy, duration of therapy and number of drugs. We’ve tried to decrease all of the treatment, of course based on trials that show that one can do that safely, but we’ve tried to get away from the highly toxic treatments that may not, in fact, give a person a significant value over less toxic treatments. And that’s actually been very well shown in the HER2-positive breast cancers as well.

Jamie DePolo: How do you talk to your patients who have been diagnosed with HER2-positive disease about their specific risk of recurrence? Do you have a different conversation with them than you would have with someone who has been diagnosed with hormone-receptor-positive disease or someone with HER2-negative disease?

Marleen Meyers: Although the scenario and the gestalt of the conversation is very similar, it has to be somewhat different because nowadays most people who come to see me have already done extensive reading or extensive talking to their friends and relatives. So, they sort of come armed with a lot of information, some of which is true and some of which is not, but a lot of that information really turns to HER2-positive breast cancer as being aggressive.

And in fact, if you go online and you read any articles or talk to people that have read articles, everyone will say the same thing, “Oh, my goodness, it’s HER2-positive breast cancer.” And part of the conversation that I try to have very early on in the conversation is to take the anxiety level down as much as possible. Because the facts are that with HER2-positive breast cancer, whether it’s in the adjuvant setting, meaning that the cancer has been removed and we’re treating for cure, or even in the metastatic setting, the outlook nowadays is really quite good.

So I try very much when I’m working with someone who has HER2-positive breast cancer particularly, I try very hard and in the beginning of the conversation to stress the good things about it. That what the HER2 blockers have done is make chemotherapy work better. We know how to use the HER2 blockers. There are several of them now which are in use. There are different ways to use them. There is more extended therapy now. And the important thing about many of the HER2 blockers is that they’re relatively non-toxic. So, unlike chemotherapy, which does have significant side effects, the HER2 blockers have relatively less side effects.

So, the main goal of the beginning of the conversation is really, in a sense, to talk a person off the ledge. Because first they hear the word cancer and then they hear the word HER2-positive breast cancer, and you almost can’t read any article online, especially in the lay press, that doesn’t make it sound very frightening. And the fact is the prognosis for the majority of people with HER2 breast cancer is quite excellent.

Jamie DePolo: That’s very good to know. Thank you. Now, are there specific ways, and I’m thinking of medicines as well as lifestyle changes, that a person could reduce the risk of HER2-positive breast cancer recurring?

Marleen Meyers: Neratinib, which is the newest HER2 blocker, it’s a very interesting new drug, which actually blocks not only the HER2, but something called the EGFR receptor. So, it actually has what we call dual blockade. And we are very excited about the data with neratinib. Currently, the approval is for what’s called extended adjuvant therapy, meaning that the standard therapy right now for women who have HER2-positive breast cancer and are treated in the adjuvant setting, for a curative intent, once they’ve completed a year of trastuzumab, or Herceptin, that’s where the indication for neratinib comes in. And the recommendations for neratinib are it’s a pill that’s taken once a day for a total of a year following the Herceptin.

So, it’s a very exciting drug. We are generally using it now for people that are at particularly high risk of recurrence. So, it’s something that we might not do only because every drug has side effects and benefits as we know. So, in someone who has a very low risk of recurrence, let’s say a very small HER2-positive breast cancer and they’ve been adequately treated, we might not use neratinib. But certainly in someone who has known positive lymph nodes and people who have been treated in what we call the neoadjuvant setting, meaning that they got chemotherapy first and then had surgery and still has residual disease at surgery, that’s someone we might look more closely at.

And again, always weighing the risks and benefits, but I think the exciting thing about neratinib is it’s a newer type of HER2 blocker. And because we’ve made such progress with HER2-positive breast cancer — the progress has been wonderful, but it is not enough. Till the day we can eradicate every single cell, that’s what we have to keep trying to do, and I think this is another good step towards that.

We do know that there are certainly lifestyle changes that are important to reduce the risk of recurrence of breast cancer and also to keep in mind that if someone has a HER2-positive breast cancer, or any breast cancer for that matter, they are at risk of another breast cancer, and the risk is somewhat elevated above the general population. And that second breast cancer might not be HER2-positive. So, when we talk about risk reduction and we talk about how to best individualize risk reduction, you’re not only looking at the individual cancer for right now, but you’re also looking ahead.

And ways to reduce the risk, there are several things that I usually recommend. Not smoking, of course, is very well known. But some of the less well-known things that one can do, which are very important, are lifestyle changes that include bumping up exercise. And what we’re really looking at is a minimum of 30 minutes/5 days a week of moderate exercise. We also look very much towards maintaining a good body mass index. So, not being overweight, eating very healthfully, having a diet that’s high in vegetables and lean protein, and eating less of everything else.

And also, alcohol consumption has become more and more important in breast cancer risk reduction. And we do know while the intermediate amount of alcohol is a little bit less clear, we do know that women who are drinking two glasses of alcohol or wine per day tend to have an increased risk. So, generally we recommend that people limit their alcohol intake to around two to possibly three drinks per week or less.

Jamie DePolo: All very good advice. Now, visitors to the Breastcancer.org site often talk about fearing recurrence. And I’m wondering if you hear that a lot in your practice and how you help your patients overcome that fear?

Marleen Meyers: I think anyone that’s heard the word cancer — it’s a life-altering word. And that goes for HER2-positive, for estrogen-receptor-positive, even for ductal carcinoma in situ, which is not a cancer that we generally expect will cause problems or recur. I think inherent in the word cancer is some increased fear of mortality for the rest of your life. And my job and my pleasure as an oncologist is to really put this in perspective. And what I like to do is present data in the positive. And by that I mean if I’m talking to someone for the first time, rather than say, “Your risk of recurrence is 10%,” what I like to say is, “If you walk out of here right now, your chance of this cancer not coming back is 90%. And what you’re here for is to make that number even higher.” And by focusing simply on that, simply on the positive rather than the negative, it puts everything really into perspective.

I also try to stress doing everything that you can do and then trying to let it be. So, what does that mean? It means when the appropriate treatment is recommended to do that treatment, although there are certainly sometimes side effects. But to try to get through the best treatment for you that will decrease your risk of recurrence. To make these important lifestyle changes, which for many, many women or men are often very, very difficult and sometimes more difficult than going through chemotherapy. Having someone eat healthfully and give up a lot of carbohydrates or a lot of sweets is sometimes much more difficult than taking chemotherapy once every 2 to 3 weeks. But that’s such an important aspect of good health and risk reduction.

We also try to stress uniqueness of every person, that there is nothing at the moment that is showing that the cancer is recurring. That they are in good health, and it’s very important to focus on that. We never know, none of us knows, what the future will bring. It’s a cliché, I know, that we always talk about, but it is a fact, and I try to leave my patients with the message that, “I would hate for us to be meeting 50 years from now,” and they have spent 50 years worrying about the cancer coming back. Each day is precious, do the very best you can do for your health, whether medical treatment, lifestyle changes, and then try very hard to move forward.

If it’s still very difficult for many people, therapy is sometimes helpful or doing mindfulness training. That, for many people, is very helpful. I stress exercise particularly because it makes you focus on yourself in a healthy way. And it’s very hard when you’re panting to think about cancer recurrence. You’re basically thinking about your health and when you finish you’re thinking about how proud you are that you got through the workout. So, doing all of these healthy things takes away from the non-healthy things.

Jamie DePolo: Thank you so much.

Marleen Meyers: My pleasure. Have a good weekend.