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    PERSPECTIVES

    HR+/HER2- Advanced Breast Cancer

    Breast Cancer Roundtable With John Whyte, MD

    Reviewed by Poonam Sachdev on February 18, 2022

    Video Transcript

    [MUSIC PLAYING] DR. JOHN WHYTE: Welcome, everyone. I'm Doctor John Whyte, the Chief Medical Officer at WebMD. Metastatic breast cancer is the most advanced form of breast cancer. More than 170,000 people are currently living with metastatic breast cancer.

    But in recent years, there's been some advancements. So to help unpack the latest data, I've asked two experts to join me. Dr. Claudine Isaacs is the Director of the Clinical Breast Cancer Program at the Lombardi Comprehensive Cancer Center at Georgetown University. And Dr. Kathleen Harden. She's the Director of the Breast Medical Oncology Program at Inova Schar Cancer Institute. Doctors, thanks for joining me.

    DR. CLAUDINE ISAACS: Thank you for having us.

    DR. JOHN WHYTE: Well, let's start off, so we're all on the same page. What do we mean by metastatic breast cancer? What does that mean to you and your patients, Dr. Isaacs?

    DR. CLAUDINE ISAACS: So metastatic breast cancer really refers to breast cancer that has spread to a distant site. So this is breast cancer that has spread beyond the breast and the lymph nodes on the same side. So the typical sites that we think about our liver, bone, lungs, brain are the typical sites that we think of when we're talking about metastatic breast cancer.

    DR. JOHN WHYTE: And Dr. Harnden, who's most likely impacted? Do we know either by type of breast cancer or presentation? And men can also be affected as well, can't they?

    DR. KATHLEEN HARNDEN: Yes. So we certainly see some men, unfortunately, with metastatic breast cancer. Women by far make up the vast majority of metastatic breast cancer cases. And women with a history of early stage breast cancer are certainly the highest proportion of those that we see.

    The highest risk breast cancer subtypes are triple negative breast cancer and previously HER2-positive breast cancer. Although advances in that field have really decreased their risk of having a metastatic or spread recurrence. Estrogen receptor positive or hormone receptor positive breast cancer is still the most common. So the vast majority of our metastatic breast cancer patients, estrogen-fueled or estrogen-driven breast cancer.

    DR. JOHN WHYTE: And then do we know what the signs and symptoms are of metastatic breast cancer? Do patients present differently or is it patients typically that have presented and then chemotherapy has failed and it become metastatic?

    DR. CLAUDINE ISAACS: So what I typically say to them is, they have symptoms that are persistent and non-improving. So it could be a cough, it could be pain, and without any clear precipitate. But it's persisting for more than two weeks and not getting better or really getting worse to contact us.

    We prefer to know about it and then we'll watch it and we'll decide whether we want to do imaging. But we really just want to make our patients aware of it, but also not kind of crazy. Right? Because they are still going to get the normal stuff and it's important to tell them that they're still going to hurt their back and still going to do those things.

    DR. JOHN WHYTE: I mentioned at the beginning that we've had advancements in treatment over the last few years. For you Dr. Isaacs, how do you think through what the treatment regimen is going to be when a patient has metastatic breast cancer?

    DR. CLAUDINE ISAACS: Well, one of the very important things is first of all to figure out what subtype of breast cancer they have. And typically, we know that from their original diagnosis. But typically what we do is we biopsy a side of metastatic disease to A, confirm that it is indeed metastatic breast cancer, and then B, to re-look at the receptor status, because our treatment is very much predicated on the characteristics of the tumor.

    And then for certain breast cancer subtypes, we also want to send additional testing, either something that can be done, the routine pathology lab like PD-L1 testing to determine whether immunotherapy is indicated or sent out for molecular profiling to help guide our treatment.

    But our treatment is really focused if they have hormone receptor positive HER2-negative, we're going down a certain pathway. They have triple-negative, we go down another one. If they have HER2-positive, we go down the third pathway. So that's how we're generally guided in terms of our recommendations.

    DR. JOHN WHYTE: And let's talk about some of the therapies because they are targeted, and that's very different than years ago when we have a limited armamentarium. So how is the field of treatment for metastatic breast cancer changed even over the last few years?

    DR. KATHLEEN HARNDEN: So the field of metastatic breast cancer has completely changed almost every few years. In the last decade or two, I feel like we are always keeping up with the latest and greatest breakthrough treatments, and each treatment that comes to market seems to make larger and larger advances in the field.

    In the field of triple negative breast cancer, some of our greatest, newer treatments are the advent of immunotherapy in triple-negative breast cancer for patients who have PD-L1 positivity, which means on the outside of their breast cancer cell, they have a marker or a receptor. It's like an arm sticking outside of their breast cancer cell that's able to evade their own immune system from identifying their cancer.

    So we have treatments that can block that hidden way of those breast cancer cells moving around the body. And then we also have new targeted treatments in triple-negative breast cancer like sacituzumab. Additionally in HER2-positive breast cancer, we have new treatments that combine a chemotherapy or a payload, as we call it, with an antibody. So it finds its way to the proper cell and deposits the treatment inside the breast cancer cell like a smart bomb.

    DR. JOHN WHYTE: And Dr. Isaacs, given the armamentarium that you have, how do you think through with the patient what's the best therapy? Is most of it routinized in terms of what you give or you really think through with the patient based on let's be practical, there are risks and benefits of any type of therapeutic intervention?

    DR. CLAUDINE ISAACS: So absolutely. We think it through on an individual basis. And I think you used a term earlier on the breast cancer journey. And I really think of metastatic disease as being a journey. The good news about breast cancer is that we have a lot of treatment options, even for the different subtypes.

    And there's often multiple choices of things that would be very appropriate to think about. So we do tend to very much individualize it based on the patient. What has her prior treatment been? How has she tolerated water or other comorbidities? What are her preferences?

    We have oral drugs, sometimes it might be preferable. So we really do try and individualize it. And it's often not a choice between A or B. But is do I do A first or B or do I do it the other way around? And that could depend on whether she is planning to go to the beach and spend a month at the beach with her family.

    So it is very much an individualized treatment. And what we're really trying to do is afford our patients the best quality of life, as they define it, for as long as possible with the various treatment options that we have available.

    DR. JOHN WHYTE: Dr. Hardin, what do we know about survival benefit in patients with metastatic breast cancer? Let's be honest, when people hear that term, it's very alarming and jarring to them. What's the latest data on five-year survival?

    DR. KATHLEEN HARNDEN: So five-year survival in the metastatic breast cancer world really depends on what type of breast cancer you have. And then in addition to that, how well the breast cancer responds in an individual to the treatments we're utilizing.

    So we can look back two decades. And many women with metastatic breast cancer that was triple-negative or HER2-positive survived for less than a year. And now we see women, particularly in the HER2-positive setting who can survive on average eight or more years with treatments that are much less toxic than what we use to offer.

    Additionally in the estrogen positive metastatic breast cancer setting, those women are living longer and better with more and more treatments that prevent them from needing chemotherapy for longer. In the triple-negative breast cancer setting, we are hopeful that immunotherapy is substantially improving survival.

    We have some studies that show that we are doubling survival in patients who are eligible for or would respond to immunotherapy. So there's a lot of hope on the horizon, and women are living and men are living longer and longer with metastatic breast cancer.

    DR. JOHN WHYTE: Well Dr. Isaacs, I'm going to go back to that journey term that you liked. So what do you tell patients who are diagnosed with metastatic breast cancer? What does that journey look like for them?

    DR. CLAUDINE ISAACS: So I typically tell them when we talk about treatment for metastatic breast cancer, we're talking about indefinite treatment. It'll be different treatments. And we talk about making choices. I say, you know, we're going to make the best choice at this time for the treatment that you're going to get right now based on the characteristics of your tumor based on prior therapies, all of the things that we talked about before.

    And at some point, the treatment that I have you on will stop working. That doesn't mean that it never worked, but it will stop working at some point. And I can't define that point. I try and give them an average, particularly if they ask for it so they can plan because I think that's important.

    But I say then at the next time point, we'll relook at things, we'll reevaluate, and we'll think about the next therapies. So I think it's really important, I think, to frame it for them that we are talking about continuous therapy.

    DR. JOHN WHYTE: And then Dr. Harnden, you mentioned that treatment seems to change every two years. So I'm going to put you on the spot. What does treatment look like in two years from now? What's on the horizon?

    DR. KATHLEEN HARNDEN: That is a fantastic question. I think that I am most hopeful that we truly find ways to allow someone's own body to detect and take care of their own cancer on a basis where we are able to take someone off of what we now consider treatment and allow for their body to really continue to fight the fight for us in a way that is sustainable.

    Now, of course, that's sort of a longer term goal probably than two years. But I think some of the most exciting things on the horizon are that we're getting better and better at detecting why cancers are able to grow around the treatment, what levers are those cancer cells using that we can then leverage against it?

    And so having more mutational targeted therapies. Really having those work better than they work now. Having more individualized basis of treating people. So I hope in the next two years, we're able to take subtypes like triple-negative breast cancer and break it down into really the different categories that it is.

    Triple-negative breast cancer became a subtype because it was sort of the not A, not B, therefore, C category. So it's not hormone-driven, it's not HER2-positive or HER2- positive. Therefore, it's triple-negative. And I think that's really a bin of individuals who have very different types of breast cancer.

    So my hope is that we're able to break that down better and we're able to leverage mutations in the tumor to work for us, as well as leveraging someone's immune system or other mechanisms within the body to fight off their breast cancer.

    DR. CLAUDINE ISAACS: I think Dr. Harnden gave a really comprehensive and thoughtful answer. The one thing that I want to just add is that the importance of clinical trials, because clinical trials have gotten us to the advances that we are at today. So all of these new drugs that we have available are really based on yesterday's trials.

    And what we really want to be doing is developing new treatments, and we're only going to be able to figure that out within clinical trials.

    DR. JOHN WHYTE: Dr. Isaacs, let's acknowledge the elephant in the room, the COVID pandemic. I want to ask you, how has the pandemic impacted the way we diagnose, treat, and manage people with metastatic breast cancer?

    DR. CLAUDINE ISAACS: It has been an interesting journey. And I think the past year and a half, it's really changed how we've looked at things. Although I think we've gone back closer to where we were. We've learned how to treat people and how to think safely.

    I think, obviously, the vaccine has made a huge difference for our patients. And the recent recommendation for booster shots for our oncology patients has really changed things. I think we look at our treatments and think about their side effects and put them in context in a little bit different light.

    But I do feel that we are in a very different place than we were, for instance, in April 2020. So I think there, we were really putting the brakes on things. And we were so worried about everything that we were doing. And I think what we've discovered is that we can continue treatment, and we can do it safely. And we are again trying to re-initiate that and not impact our patient's long-term livelihood because of COVID.

    DR. JOHN WHYTE: Dr. Harnden, I want to give you an opportunity to talk to viewers who have been diagnosed with metastatic breast cancer or maybe it's a family member or loved one watching this program, what's your message to them?

    DR. KATHLEEN HARNDEN: It's a great question. I think that the most important part of the journey for most individuals is feeling that they have the support of their family and friends and their greater network to make the decisions that are right for them at that moment in time. And so being that source of support, being a listening ear, and being a part of their journey where you enable them to feel comfortable to make an individualized decision that's right for them without feeling undue pressure and other directions.

    I think for women and men actually facing metastatic breast cancer know that there is a lot of hope that people individually and as a group continue to outlive and outlast our greatest expectations that people continue to do fantastically well with the latest and greatest treatments. And that clinical trials are on an everyday basis establishing new breakthroughs for us in the field of metastatic breast cancer.

    DR. JOHN WHYTE: Well, Dr. Isaacs, Dr. Harnden, I want to thank you both for taking the time, as I mentioned at the beginning, to help unpack what is the latest information about diagnosis and treatment of metastatic breast cancer.

    As you both point out, it's important to make sure you get the best care, to have a good relationship with the physician and ask questions, and make sure they're aware of what's on your mind. Thanks for watching.

    DR. CLAUDINE ISAACS: Thank you.

    DR. KATHLEEN HARNDEN: Thank you.

    [MUSIC PLAYING]

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