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Published on August 26, 2020
What Metastatic Breast Cancer Treatments Are Available?
What are first-line treatments for different subsets of metastatic breast cancer (MBC)? When do clinical trials fit in? What is the role of biomarkers when deciding treatments? What treatments are in development that experts are excited about? In Episode 4 of our Let's Talk Metastatic Breast Cancer series, patient host Kelly Shanahan and Tigerlily Foundation advocate Nunny Reece answer these questions with input from experts Dr. Natasha Hunter of Seattle Cancer Care Alliance and Dr. Marleen Meyers of NYU Langone's Perlmutter Cancer Center. Watch to hear the full discussion.
This series is sponsored by Seattle Genetics. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.
Transcript | Let's Talk Metastatic Breast Cancer: What Are My Treatment Options?
Hi, thank you for joining us today. I'm Kelly Shanahan and welcome to episode four in Patient Power's Let's Talk Metastatic Breast Cancer series. In our last show, we talked about the tests and scans associated with metastatic breast cancer. If you missed it live, you can watch the replay on patientpower.info. Today, we're going to talk about treatments for metastatic breast cancer.
I'm excited to be joined today by two breast cancer experts and a Tigerlily ANGEL advocate. And it is my great pleasure to ask Nunny Reece, a fellow person living with metastatic breast cancer and an ANGEL advocate with the Tigerlily Foundation, to please introduce herself and tell a little bit about her story.
Hello, Kelly, and thank you. My name is Nunny Keyla Reece, and I was diagnosed in 2017 at the age of 39 with metastatic breast cancer de novo. Since my diagnosis, I have gone through a few different... chemotherapy, hormone therapy treatments, radiation, and kyphoplasty and some other types of surgery as well.
Before all of this came about, I was living a normal life. Well, what seemed to be normal. And I was a certified medical assistant for over 15 years. I'm married to my husband, Scott, for 20 years. We have three wonderful boys, and I was very active, had a lot of hobbies, spending time with my family, going to the beach, planning outlandish things that I usually like to do. And then out of nowhere, I was hit with stage four breast cancer.
Thank you for sharing your story, Nunny. I was diagnosed with early-stage breast cancer, and five years later was diagnosed with metastatic disease. In my former life, I was a physician, but believe me, all of that left my head the minute I was given my metastatic diagnosis. Dr. Meyers, I'd like to ask you, how do you decide what treatments to offer a patient newly diagnosed with metastatic breast cancer? Whether it's a de novo, from the get-go diagnosis, or whether it's someone like me, who became metastatic after an early-stage diagnosis.
Thank you, Kelly. I'm so delighted to be here today. And I think the first thing that I look at is really what we call the biology of the tumor. And that basically means, how is a person's breast cancer going to behave based on some of the proteins on the cell surface.
So specifically, I would look to see, is somebody's estrogen receptor-positive, are they HER2 positive, are they triple-negative? And that helps guide the type of treatment that I would consider giving somebody. Of course, very importantly, we also have to consider a person's performance status, how they feel, what their extent of metastatic disease is, are they asymptomatic. In other words, they have no symptoms. And this was found just out of the blue or does someone have a particular symptom that has to be addressed, such as bone pain, that may require radiation.
And then we sort of go through the armamentarium, looking back at what a person has had, if they've been previously treated, how long has the time been since their early breast cancer diagnosis and the recurrence. Or in someone who is de novo we have more options because they haven't been treated before. And once all of these things are put together, then I sit down with my patients. We have a long discussion as to goals of treatment, patient preference, or are they looking for something more investigational, or are they looking for something more standard of care to start? And very importantly, what are expectations of treatment? Can we expect the tumor to shrink? Can we expect it to go away? How long? And all of those really come into the first discussion about metastatic disease.
It's incredibly overwhelming when we hear that news.
For someone that's new and really don't understand biomarkers, to help them understand, what exactly does the biomarkers... How did you determine which biomarkers would help, as far as the best decision for the patient?
That's a great question. And that's some of the core information that I would have when I see somebody for the first time. And basically that information is given to me by the pathologist. And what I always like to do is draw a picture, because I think one picture is worth a thousand words. And I often describe a cancer cell, almost like a little human. And the way I describe it is that the way we have external characteristics, we have genetic characteristics on our surface. We have certain hair colors, certain eye color.
If you think of a cancer cell, a cancer cell has these external characteristics, too. Of course, they don't have hair color or eye color, but they have something called receptors. And basically the three key ones that we look at are estrogen receptor, progesterone receptor, and HER2. And that helps define how the breast cancer cell will behave. And then we can try to target those receptors by using medications that may directly attack the receptor to give us a better outcome. So it's a pathology information that we get, but a very, very important part of the core of discussing breast cancer with anyone.
Dr. Hunter, I'd like to follow up with you. I know that you do research on biomarkers, in addition to the typical pathologic receptors that we all know about, ER/PR in HER2. So what do you see the role of biomarker testing, genomic testing, and other biomarker testing in treatment decisions around metastatic breast cancer?
I think it's a great question, and it's a complicated question. Biomarkers fall into a couple different categories. Basically, biomarkers mean some form of learning more about the breast cancer and predicting how it will respond to various therapies. But they fall into, I would say, roughly two categories, and one is more diagnostic in terms of understanding the characteristics of the tumor and maybe predicting the therapies that they might respond to. And the other would be monitoring response to therapy. So monitoring levels of what we call tumor markers and seeing whether we think that the tumor might be responding to therapy, or maybe becoming resistant.
Keeping in mind that those are a couple of different categories, metastatic breast cancer is interesting in that in addition to the traditional or more standard early-stage biomarkers that Dr. Meyer was talking about. And I really liked that analogy of the characteristics of treating the cancer, like a small human. I'm going to use that. But in addition to the ER/PR in HER2, we standardly in the NCCN, the National Comprehensive Cancer Network guidelines, do recommend that at the first diagnosis of metastatic breast cancer, that a biopsy is performed and that that biopsy be sent for molecular markers.
Our choice of which molecular markers to send, and when to send them, depends a bit on, what we already know about the cancer. So whether it's ER/PR positive or HER2 positive helps guide some of the decision making around sending, at least... I should add a caveat, at least in our institution, because we send for individual tests. So in terms of molecular testing, for example, if a patient is ER/PR positive, then we are interested in whether they might, and this is a very recent development in metastatic breast cancer, whether they might have a mutation in the actual tumor.
So that's different from the mutation that you might pass along to your kids, or that you might have gotten from a parent. But a mutation that your tumor has developed that helps it grow and divide. So one of those mutations for ER/PR positive breast cancer is PIK3CA. So that's a very common mutation that tumors develop, and about 40% of ER/PR positive breast cancers have that mutation. And it can help us understand that that tumor might respond to what we call a targeted therapy. So, a non-chemo-therapeutic drug that targets that particular pathway that that PIK3CA mutation gives us a hint is active.
Alpelisib (Piqray) is a new drug that was recently approved, I believe in, it might've been May of 2019. Anyway, very recently. And I think we'll begin to see more and more of these drugs coming down the line, helping us to understand matching mutations with actual therapy, and kind of opening the door to new kinds of treatments.
So that's one kind of biomarker, and I think PIK3CA is a good example of it. Other examples include PD-L1, which helps us understand possible response to immune therapy. And then lately we've been looking at ERBB2 mutations that may help us, even in patients who are not classically HER2 positive, they may actually respond to certain kinds of HER2-directed therapy. So I think all of those are exciting areas of research.
On the other side of things, the idea of monitoring a patient's response to therapy and trying to figure out whether that tumor is developing resistance, or whether it's responding. We currently have some quote-unquote tumor markers, and probably many of you are familiar with monitoring markers, such as CA15-3 or CEA, sometimes CA-125. And all of those have kind of varying levels of sensitivity in terms of how much they tell us about a tumor's response. I've certainly seen patients who don't have any bump in any of those biomarkers, despite having a pretty strong burden, or a pretty heavy burden of disease. And then other patients where you can find a biomarker that really does seem to track along the therapy quite nicely. So it's really very idiosyncratic, but they are useful in certain situations.
We are in the process, I think, of developing more sensitive biomarkers, especially in the last couple of decades. The ability to sequence genomically and find mutations that we can follow, and also look at things like circulating tumor DNA. So the tumors themselves, as they begin to die and shed DNA into the bloodstream, we can detect some of those mutations in the bloodstream and begin to see quantitative levels of those over time, to see response to therapy.
I promise not to say something that wasn't ready for prime time. I think it's actually nearing prime time, and I think we're seeing more and more promising results from that area of research in terms of, specifically, DNA-based blood tests looking at response to therapy. The cost of those kinds of therapies, and the quantitative, or the computing power over the last couple of decades, has just increased exponentially. And so there's a lot going on in that area and I'm really hopeful.
What if you can't get enough tissue from a biopsy to do biomarker or genomic testing, what's the next step then?
Sure. So there are a couple of situations where that occurs. Obviously there's some situations where you can't actually get the biopsy, where the location of the tumor is not amenable, or the tumor may look diffuse. You may have diffused lung metastases, but you don't have a lot of hope of getting an actual significant piece of tumor with a biopsy. The other situation that we see a lot is with bone metastases. About 15% of patients present with metastatic bone disease that's really predominantly, or even solely, in the bone. And so in some cases, unfortunately, what we find is that those are de novo patients. And so in that case, it's rare, but in that case, you really have trouble getting any tissue at all to evaluate the tumor.
But even if you just have bone metastases, the decalcification process, in a lot of institutions, renders a lot of the proteins and DNA that we would normally use to test the tumor, even for ER/PR and HER2, but certainly for molecular analysis, meaning DNA analysis, it tends to ruin those proteins. Essentially, you're taking a piece of tissue and dropping it in a bunch of acid, and that denatures a lot of the relevant tissue.
So I think there's a couple of options. In terms of bone disease, our institution always denatures the tissue in EDTA. Doesn't matter what that is, but it's a process that preserves all of those proteins, so allows for testing. In patients where there is no ability to get tissue, I think more and more we're turning to liquid biopsy. There is a platform called Guardant360, and I think that's the primary one that people are using, at least here on the West Coast, to evaluate possible mutations. ER/PR and HER2 are not able to be evaluated through that medium, but at least we can look for some tumors, what we call tumor-specific mutations, and use those to help us guide possible therapy options.
Yeah. Thank you. And, you know, from a patient standpoint, we certainly would prefer to have blood drawn, than have needles stuck in various parts of our bodies. Dr. Meyers, I'd like to ask you a question about triple-negative breast cancer, and specifically, treatment options. You know, triple-negative has always been the one that there are no receptors, but I think we're learning now that PDL1 status may impact treatment choices. Immunotherapy may have some promise in triple-negative. So how do you go about what that, that patient that comes in newly diagnosed with biopsy-proven triple-negative metastatic disease?
So that's a great question. Triple-negative has always been the sticky wicket of breast cancer. It's not common, but it is the kind of breast cancer we worry about probably more than any kind of breast cancer. Specifically, because to date, there's not an obvious target. So if someone has positive hormone receptors, we can target that. If someone has an amplified HER2, we can target that. But it's sort of like having, in a sense, what looks like a naked cancer cell. So you sort of feel you have to try to kill it with chemotherapy. And the problem with that is, chemotherapy kills rapidly dividing cells by definition, that's what chemotherapy is, chemical treatment, but we have so many other rapidly dividing cells in our body. And the response of triple-negative breast cancer tends to be not so great. So you end up having a lot of toxicity with a relatively low rate of success, in terms of trying to shrink the tumor and alleviate symptoms. So the excitement of harnessing our immune system is really a whole new field for treatment of breast cancer, particularly triple-negative breast cancer, but other breast cancers as well.
And commonly these drugs are used in combination with chemotherapy. There are several in clinical trials now, particularly used with Taxanes. So, such as Paclitaxel (Abraxane) or Taxol with PDL1 drugs, but there's a whole host of targeted therapy now that's being tried in triple-negative breast cancer. And I can tell you that from a practical standpoint, they are generally tolerated well, but do have a toxicity that can be very worrisome and may not be for the faint of heart. So one really has to consider when giving these drugs. So things like pembrolizumab (Keytruda), for example, that can have immune toxicity, things like thyroiditis, carditis, any kind of inflammation of any body organ, that you have to really alert the patient. And this has to be really an ongoing conversation with someone. Do you want to use this combination, chemotherapy plus immunotherapy? Or do you want to just start with chemotherapy first?
So a lot goes into this decision, but I think the trend, based on trials that were presented at ASCO and based on a lot of the new data we have, it seems like the best combination is chemotherapy with immunotherapy.
I know we just was mentioning triple-negative, but what about for ER-positive and HER negative? What is the first line of treatment that is good for the ER-positive and HER negatives? I have a lot of ladies that ask about that.
So, ER-positive. I think the reason, Nunny, that you're getting a lot of ladies who are asking that, is because it's the most common type of breast cancer. It tends to be the type where people do very well and have longer survivals, and respond to treatment very well. And the first treatment typically depends on whether someone is presenting de novo. So they're presenting with metastatic disease, or they've been on hormone therapy in the past, in the adjuvant setting and now have a recurrence, or they'd been off hormone therapy for many years and now have a recurrence.
But in general, the first-line treatment is going to be a class of drug called an aromatase inhibitor. And even if that means making somebody, or rendering them, post-menopausal when they're younger, we tend to do that, give them an aromatase inhibitor, which is a hormone blocker, and then add a CDK inhibitor to that. And that has been shown to improve overall disease-free survival, overall response, and has really been a boom to treatment of metastatic ER-positive breast cancer.
And recent trials have shown with ribociclib (Kisqali), actually, an improvement in overall survival, how long it is before we actually croak and die from this disease. So that is ultimately the goal. How come we have to give chemotherapy and immunotherapy? Why not just immunotherapy alone?
That's a great question, and the truth is we actually may not have to give chemotherapy. Immunotherapy may work well as well. And I think we're in the midst of clinical trials looking at that. And one good example is, not to give my age away. I already gave my location away because of my accent, but not to give my age away. I do remember vividly the HER2, the Herceptin, the trastuzumab clinical trials in the 1990s, and trastuzumab for HER2-positive breast cancer was almost a miracle, I guess it's the only way I can put it. It was a miraculous drug. And we used it initially in clinical trials by itself, and it worked, and it was okay. But as soon as we put it together with chemotherapy, it was truly miraculous. And we would see people come in with pulmonary, with lung metastases and extreme shortness of breath, and they would get the drug and a few weeks later they'd be sprinting in and just feeling great. And it was truly miraculous.
And I think we are on a very, very long and steep learning curve with therapy, other than chemotherapy. We have a lot to learn, a lot to discover. So it in fact may turn out that immunotherapy alone might be fine, and might be perfect. It might be the drug of choice for some people with triple-negative breast cancer. I don't know that we're at that point yet, to be able to say that.
Yeah, there's always been the thought that breast cancer is an immune cold tumor and that it's not going to respond to immunotherapy the way that other cancers like melanoma, for example, do, but we are starting to get some promising results from clinical trials. Speaking of clinical trials, when do you discuss the option of a clinical trial with your patients? Dr. Hunter, would you like to start with that one?
Sure. I mean, I think it really depends on the kinds of clinical trials that we have available. I mean, in general, I think... As soon as my patient is diagnosed with metastatic breast cancer, I at least start trying to talk with patients about clinical trials, because I think there's a lot of misconceptions about what clinical trials are. I think there's a common idea that we're making patients lab rats, that we're experimenting. And really... Certainly, there have been some terrible things that have happened in the past to destroy trust between physicians and patients. So I think we have to acknowledge that.
But I think currently, it's important to very early on start talking about clinical trials because what clinical trials at their best do, is combine a standard therapy that we know is effective, that's been approved, with something that we think is a good idea, and compare that against that standard of care. And so I think that when, when patients... And that tends to be when there is a standard of care, there certainly are clinical trials sort of later on, at later lines of therapy, where we don't have a lot of options or we don't have a lot that's standard. Obviously I think many of you have... At least my experience is that as patients go further along in their lines of therapy, their choices become very individualized. And so, there are some situations where there may only be a clinical trial that's available, in which case there's no real standard to compare it to.
So clinical trials vary, but what I would emphasize is that it would never be ethical to offer only a clinical trial, meaning something that might seem like it's a good idea, if there is a standard therapy that works really well. For example, we know that the medication that Dr. Meyer was mentioning, a CDK inhibitor, works really, really well in ER-positive breast cancer. I would never offer a clinical trial offering some untested medication against CDK4/6 inhibitors because I know that that's not ethical. But I would offer a CDK4/6 inhibitor, plus something that's exciting, versus that same CDK4/6 inhibitor.
So that's how I think about clinical trials. And then the discussion becomes a very individualized one, and it's individual to the patient, and it's individual to the institution as well, because all institutions have kind of a variety of clinical trials that are available, and some may or may not be good fits for patients. And so depending on the patient, how mobile they are, how aggressively they want to pursue clinical trials in various areas when it's possible for anyone to travel, that comes into play. And then also obviously the clinical trials that are available at our particular institutions and what might be a good fit for the patient.
Dr. Meyers, do you have anything that you'd like to add to that?
So, yes, I think that was a great summary of what clinical trials are all about. And it's important to remember, I think two other things. One is that in the metastatic setting, we don't do clinical trials where someone is randomized to placebo versus the treatment. So I know that patients are often very, very scared of entering clinical trials, because of that concern, that they may be given nothing or a sugar pill. So it's really important to explain that in this setting, people are not randomized to placebo versus something else, they're randomized to the known treatment versus something else. And another important thing, I think, as clinicians, that we always think about when we see a person that are thinking about clinical trials is the eligibility criteria because we don't want to lose a window of opportunity. So for example, in the metastatic setting, there may be a new and exciting drug or a combination of drugs, but the eligibility may say, you can only have had one chemotherapy drug before it.
So we always have to keep this in mind in planning a trajectory when people come to see us and they're so frightened, and it's a first diagnosis of metastatic breast cancer, and they can barely put things together because of the fear, we have to be looking ahead and saying, okay, this is step number one. If this works great, if not step number two is this. So we're thinking three, four steps out to take into account the eligibility criteria.
Right. And, I think as someone who lives in a rural area, I need to remind both of you, that not everyone goes to an NCI designated cancer center or has one in their backyard. And then it's also from the patient's standpoint, we want to hear about trials, not necessarily just the ones that are in our backyard, but ones that we may be eligible for, even if it requires trial.
I have one question and that's because I get people asking me this a lot as well. As an African-American female, and I'm on my eighth round of treatment, what would you say to me, or to your patient, in lines of trust and clinical trials? I know we talked about clinical trials, but one of the things is trust. What would you say to me as far as trust and clinical trials?
As someone who came from Johns Hopkins, which has a fairly ugly history in terms of African-Americans in clinical trials, and as someone who in fellowship treated a lot of African-American patients where that was an issue that came up, I usually try to speak pretty openly to that. When I have a conversation with a patient about clinical trials, I think that it's important to build trust. There's been a lot that's happened that's broken that trust, and I think the first step in trying to rebuild that as being transparent about our history, and talk with the patient about their concerns and their fears, and try to meet them where they are and explore that relationship. Because I think it's a very individual relationship with a patient, and it has to be done with transparency and respect.
I completely agree. I think that's perfectly said, and at NYU Langone, we have a very strong relationship with Bellevue Hospital, which of course has multi-ethnic population. And it is... I think building trust, it has to be on an individual level. It's not trust within a group. It's a doctor-patient relationship. And I think it's particularly important for people who have stage four disease, first and foremost, to have that relationship, because it is a lifelong-term relationship. And if you don't trust your doctor, or your nurse practitioner, or whoever is taking care of you, you're not going to trust them whether it's a clinical trial, whether it's standard treatment, whether it's a recommendation to take an antidepressant, whether it's a recommendation to exercise. If you don't trust somebody, you don't trust them. So that is first and foremost, you have to be one with your care provider. This has to be a lifelong relationship.
Thank you, Nunny, for asking that question. And as someone who's known for being shy, retiring, and not afraid to speak my mind, I just want to remind you, Dr. Meyers, you, Dr. Hunter, and every other clinician and researcher out there, that by involving advocates in the design of your trials, you will have better trials. By inviting a diverse group of advocates that reflect the population that will eventually use the drug, you will have a better trial. Ask us. It's like "Field of Dreams," you know, "Build it and they will come." Ask us and we will be there for you. Nunny has a great, great cohort of people in her community. I know a ton of people. We can help you make better trials that can enroll a diverse population of patients so that the drugs that come out of these trials work better for more people.
So there's my soapbox and I'm going to get off of it now. We're getting close to the end. So I want to asking each of you what you are most excited about, that's coming down the pike in terms of treatment. And we haven't talked much about HER2 positive, if there's anything coming down for HER2, that'd be great to hear about that. But you know, again, if each of you can give us an idea of what you're most excited about that we may not as patients know about, but you guys know that's heading down the FDA pike.
I am so excited about so many things because we have seen over the past year such a boom in new drugs that are approved by the FDA, largely the HER2 targeted therapy, drugs like tucatinib (Tukysa). So there've been a whole boom of new drugs, which are really exciting. One thing I'm very excited about is a new drug called elacestrant for estrogen receptor-positive breast cancer in people who have failed CDK inhibitors and hormone therapy.
Okay, I'm going to interrupt you right there.
People do not fail therapy, therapy fails the people.
Okay. You are absolutely right. You are absolutely right. So when therapy fails the person who has estrogen receptor-positive breast cancer, who has had hormone blockers and a CDK inhibitor, this is really a new type of drug, which is very exciting. Because keeping in mind that estrogen receptor-positive breast cancer is the most common, and therefore it's going to affect the greater percentage of women going forward. But I'm also excited conceptually about a lot of other changes in oncology, largely drugs that are now being formulated in the oral setting. So we can get away from people feeling sick and having to go to an office for their treatment. Drugs that are being... Such as trastuzumab that instead of having to get an infusion, you can get under your skin.
So I'm excited about the human aspect of the survivorship in metastatic breast cancer, where people, although they are dealing with metastatic breast cancer, they also have a very full, wonderful life. And the more you can keep people away from the doctor, really, the better it is.
Yeah. And especially now in the era of COVID, things that we can self-administer at home, like a sub-Q injection or oral medications, are a boon to us. Dr. Hunter, what about you? What are you excited about that's coming down the pike?
Sure. I would second everything that Dr. Meyer just mentioned. I think that while it's on my mind, I would mention that I would very much agree with her thoughts about the quality of life drugs, drugs that are meant to improve quality of life for patients with metastatic breast cancer, including the injectables. I'm the PI of a study where we're doing a home nurse-injected, Herceptin and Pertuzumab (Perjeta), so that patients don't have to leave their homes. They can have somebody come to their homes and inject, it's not self-injection, but it at least is somewhat more convenient than having to come to a cancer center. Oral SERDs so that you don't have to get two shots every 28 days, for fulvestrant (Faslodex), I think is another one.
But I think in terms of the more, sort of the cancer-directed therapy, that's more revolutionary, I think that because of my research and my interests are in molecular markers, I'm excited about AKT inhibitors. There's a couple of AKT inhibitors. AKT is a mutation that occurs in somewhere, not common, but six to seven percent of metastatic breast cancer. And I think those have shown really interesting activity in both ER-positive and triple-negative breast cancer. Another, FGFR2 inhibitors. FGFR2 is a hallmark of very aggressive breast cancer. And I think that we're beginning to see... I've certainly seen off-label uses of FGFR2 inhibitors that seem to be somewhat effective in that disease.
And so I think that those are, um, those are some exciting developments, but I think that what's exciting to me is sort of a general sense that our ability to learn more about the disease and respond, is, is really exponentially growing with our ability to process data and gather molecular information at a level of... At a volume and a cost that's been unheard of in the past. And so, I think that it's a really exciting time. It's a bit of a Wild West, but I think it also is very, very exciting and hopeful.
Thank you. I'd like to thank all of you for joining us. Thank you to the audience for tuning in. So join us for our next program. And you can send any questions that you may have in advanced to email@example.com. I'm Kelly Shanahan, and remember, knowledge can be the best medicine of all.