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Melanie Cole (Host): Welcome to UAB Med Cast. I'm Melanie Cole. And today we're discussing the future of breast cancer treatment. We're going to be talking about the era of targeted therapies in triple negative and HER2 positive breast cancer, how genomic assays help to guide treatment options and how the specialists at UAB Medicine are using patient reported outcomes to guide patient care. Joining me in this panel round table is Dr. Erica Stringer-Reasor, she's an Associate Professor of Medicine in the Division of Hematology Oncology, and she's the Director of the Breast Program at UAB.

Dr. Ahmed Elkhanany. He's the Assistant Professor of Medicine in the Division of Hematology Oncology at UAB and Dr. Gabrielle Rocque. She's an Associate Professor of Medicine in the Division of Hematology, Oncology, and Gerontology, Geriatrics, and Palliative Care at UAB Medicine. Doctors, thank you so much for joining us for this fascinating panel today. And Dr. Stringer-Reasor, I'd like to start with you. Tell us a little bit about triple negative breast cancer. What makes this cancer more challenging? And what are some of the common features of this type of cancer?

Erica Stringer-Reasor, MD (Guest): So triple negative breast cancer is one of the most aggressive subtypes of breast cancer that we actually treat and diagnose. It often occurs in young patients. And it often disproportionately affects young minority patients, specifically, black American patients. We do know that it has a high doubling factor and so growth rates happen within weeks to months as opposed to some other breast tumor types, such as hormone driven breast cancers that double or grow within months, two years. So certainly is a very aggressive subtype of breast cancer, which unfortunately has very limited amount of treatment aside from chemotherapy.

Host: Well, then tell us about the exciting era of targeted therapies. I've done shows, so many of them on this and it's such a fascinating and exciting time in your field. Tell us how they're being used for triple negative and HER2 positive breast cancer and some of the most exciting treatments that you, yourself are excited about.

Dr. Stringer-Reasor: So recently, there have been a few discoveries in triple negative breast cancer because of it's growth rate is so fast, there have been very difficult tasks for scientists to tackle, to actually target these mutations because they evolve within weeks to months. And so, currently again, the main thing continues to be intravenous IV chemotherapy. But recently, over the last year there was a smart drug called, an antibody drug conjugate called cetuximab velatekm, that was, genetically engineered and now FDA approved to treat this aggressive form of breast cancer. Well, what's even more interesting on this study in which this drug got approval is that patients had had several lines of chemotherapy and their bodies tended to respond well to the chemotherapy.

So, I think that this is an era where we're now seeing that we can target this tumor more effectively. Most recently we also gained some data on, triple negative breast cancers, as it pertains to BRCA mutations and found that tumors that did express this BRCA I or II mutation, may also in fact, respond to a PARP inhibitors. Which again, we will also see this mutation oftentimes in triple negative breast cancer. So, this also brought us the horizon, for patients diagnosed with late stage triple negative breast cancer.

Host: Thank you so much, Dr. Stringer-Reasor. Absolutely fascinating what's happening. So Dr. Elkhanany, tell us a little bit about the roots of advanced genomic testing. How did this mark a dramatic shift in the understanding of cancer and other diseases?

Ahmed Elkhanany, MD (Guest): I think, genomic testing has drastically changed the landscape of breast cancer. Cancer care in general and spun off what we now call precision oncology, which is really the idea of choosing the lines of therapy for patients based on the behavior and the driving forces that make up the genes within their specific cancers. Now, breast cancer fits in a different area altogether compared to some other standard cancers because gene testing, comes in many different aspects of breast cancer care as far as early stage 1, 2 and 3 breast cancer and what we call gene expression profile, which scans the space, not just the prognosis of patients, but also the benefits of different therapeutic modalities, such as chemotherapy and endocrine therapy. And it also comes towards the other side of the spectrum with stage 4 breast cancer, where it can inform us of what we call actionable mutations in the tumor cells. And it can inform us about certain genomic makeup that makes patients, for example, would predict a benefit from one particular treatment or the other.

So to guide, for example, one of the common tools that depends on the gene expression of cancer is what we call Oncotype some other tools similar to it, including MammaPrint, EndoPredict, and all of these tools look at the breast cancer at the time of surgery and look at specific sets of genes that can predict whether or not these patients will benefit from chemotherapy and how would they do 10 years down the line.

If we take a minute to pause and ponder about how 16 genes that can be taken from the time of surgery for patients can tell them how they will do 10 years down the line, I think that's very inspiring and really groundbreaking. In the advanced setting and using what's called next gen sequencing, which has become our go-to tools to understand genomic behavior of cancer. We're able to go on in, on at least what's growing now to be, in the tens of mutations that are actionable, meaning that we have targets that can help clear are the course of the disease. And some of the more notable examples include the PIK3CA mutation as well as some other DNA repair mutations, but the BRCA 1 and BRCA 2 and the mutations that infer resistance to certain therapies such as ESR 1 mutations and all of these tend to have little bit of an impact in the treatment course of patients down the line.

Most notably, some other mutations that for example, that we have understood from other cancers that some of the treatment paradigms introduced to breast cancer, like Edo foreign Arab, P two mutations, which now we understand also can be drivers of 10 cancer subtypes and all in all, I feel like this is a very exciting era for breast cancer where we're able to not only treat with the next big thing, but treat it on a personalized level. So, we're doing just the Goldilocks level of care.

Host: Certainly that is an ultimate goal. Now, Dr. Elkhanany it's important for referring physicians and I'd like you to speak to them for just a minute that these physicians may know the patient very well, have a long history with them and be able to counsel them on choosing wisely. Can you tell us a little bit about when they are counseling their patients about genomic assays and how they help to guide some of these breast cancer treatment options specifically, what you want them to relay to their patients about this exciting time in your field. And, while you're answering that, as researchers have taken the advancements one step further with genomic tests of the cancer itself, tell us how we've advanced regarding genome testing.

Dr. Elkhanany: So I think, what part of the advances in genomic testing is that it becomes the methodology and the underlying cost of the steps have decreased substantially. And at the same time, our ability to use these tests in clinical settings and being able to actually apply to our patients have also been proven to be applicable, with new numerous trials that are trying to put all these information in a clinical setting.

For example, one of the two larger trials in breast cancer, like RxPONDER trial and TAILORx have used that test we call Oncotype to try to tell us who will benefit from chemotherapy and to what extent is that benefit going to be? And, in this note, we have managed to deescalate or decrease the percentage of patients that we'd recommend chemotherapy to by a substantial number.

And there was a very interesting story about that in New York Times. When some of these trials, came up in 2019 and 2020. I think it's important for the referring oncologist to have an honest discussion with patients about what these assays can and cannot do. And at the end of the day, they're all approximate, reality. But sometimes even with these assays, we have to individualize the care to patients. And a lot of them, unfortunately still give us gray zone areas where we still have to sit down with the patient and dig down into the numbers and tell them, this is your benefit on the treatment or off the treatment and have a mutual decision making process with the patient.

But at least we live in an era where some of these tools have come so far ahead that they're not just a numbers in computers anymore, but they are real live tools that can tell us how patients will do. And I'm excited for the future and what these tools will allow us to do going down the line.

Dr. Stringer-Reasor: And the speaking of the future, I just wanted to add one additional point to what Dr. Elkhanany was just speaking or alluding to. We know with all these genomic tests that beyond just targeting the therapy, at the present time, we want to be able to target the best therapy the first time, to really help prevent relapses and recurrences of the disease. And I think as we begin to tailor, and modified these genomic assays, we'll be better able to understand the particular molecular subtype of these tumors. And in fact, choose the best therapy for the patient the first time, in hopes of again, decreasing the risk of relapse in the future. So, I think that, that's where the field of medicine is heading.

Host: Dr Rocque, we have not forgotten you, but I'd love for you to talk about patient reported outcomes. What are some of the advantages to help guide patient focused care and the potential benefits of patient-centered care?

Gabrielle Rocque, MD (Guest): So, patient reported outcomes are really gaining a lot of traction in the field right now. So, years ago, we recognized that survival and symptoms really aren't the only important things to patients when they're making treatment decisions and when they're going through their cancer journey. And furthermore, that physicians frequently missed symptoms that were important and meaningful to patients. So, we discovered that if we asked patients directly to complete patient reported outcomes and tell us initially what their symptoms and later quality of life and other measures are, that we have a much better understanding of that patient experience.

So, you'll see that clinical trials now typically do include a series of patient reported outcomes, and that data can help us identify what are the issues that are relevant to particular medications when we're choosing those therapies for our patients. So, if a patient has a particular priority, for example, they're a piano player and we're worried about nerve damage from a drug. We might steer away from that. If we know that the patient reported outcomes has told us that this is a particularly problematic side effect for a particular medication. In addition, it also helps us tell our patients what to expect so that we can indicate, what should they be anticipating for quality of life, for symptoms, for mood, for fatigue, all kinds of different aspects that are critical for us to follow.

And then finally, it's also important to understand that those patient reported outcomes often can guide approval of medications because in some cases we're looking for pain reduction for example, in some metastatic cancers. And so having that patient reported data is really critical when we're thinking about clinical trials. There's also a entirely new area of patient reported outcomes, and that is using this as part of standard of care to better monitor and manage our patients. So, that's something that we're doing here at UAB currently, in which we are using patient reported outcomes on a routine basis to guide the care we deliver, to connect them to appropriate supportive care services, like our psycho-oncology program, as well as to identify symptoms proactively, to be better able to identify problems early, to reach out to those patients and manage them in the best possible way. And previous literature in this space has shown that if we manage patient symptoms and patient concerns more proactively, that we do see improvements in their ability to stay on treatment, their quality of life, reductions in hospitalizations and emergency room visits, as well as in some cases of advanced cancer, improvements in survival.

So this is an area where both from clinical trial perspective, as well as the standard of care perspective, there is lots of opportunities to enhance patient centered care and provide the best possible quality of care.

Dr. Stringer-Reasor: And then I kind of want to just add on to what Dr. Rocque stated about how important these patient reported outcomes are to clinical investigators and patients and advocates as we develop new drugs and new targeted drugs. And years ago, and you will still see it sometimes now, that as you develop new drugs, especially the early stage development of drugs, there's always this nomenclature of finding the maximum tolerated dose. And so that means that in these studies, these drugs would start at the low dose and go up to these very high doses of the drugs. And thinking that the higher, the dose of the drug, the more efficacy or the better it works. But in fact, we have utilizing next generation sequencing and utilizing things called circulating tumor DNA and the tumor and looking for better targets to our drug therapies; we found that you don't always have to have the highest dose of a drug to get the best efficacy. And, these patient reported outcomes that have been instituted into many national clinical trials, have been really pivotal in letting us know how patients are actually feeling and getting subjective data on how the patients are doing while on these study drugs. And again, that's made clinician scientists, even more aware of how drugs can be helpful, but they also may cause some side effects.

And so there is a balance in getting efficacy, and also good quality of life. And so I'm so excited that patient reported outcomes over the last like five years have really escalated our care to patients and hearing their voice and how we develop newer and better drugs.

Host: I feel that's one of the most important aspects that you all are discussing here today. And I'd like to give you each a chance for a final thought and Dr. Stringer-Reasor, I'd like to start with you. As we're talking about this era of targeted therapies and this exciting time in your field, what would you like other providers to take away from the Breast Program at UAB Medicine, and the multidisciplinary care, the importance of that multidisciplinary approach that you use for your patients?

Dr. Stringer-Reasor: I think that breast cancer treatments have definitely evolved over the last 10 years. At the O'Neill Comprehensive Cancer Center, patients are able to get a personalized, a specialized approach to their cancer care and also help be an active voice in the decisions that the team helps to make. And so when patients are newly diagnosed with their breast cancer, they get a team of doctors from a surgeon, a radiation oncologist, and a medical oncologist that they meet at the same day in the same room and all of the imaging tests and labs are all evaluated and they walk out of the clinic with a concise plan. And so, the era of targeted therapy and all of the new drug therapies that have been FDA approved, have really helped us better treat our patients and definitely helped to decrease the risk of relapse. And I think that for patients diagnosed with later stage diseases, over the last two years, there've been four drugs approved for an highly aggressive, HER2 positive breast cancer.

We just talked about two drugs in triple negative breast cancer. So, I'd just like to say that because of the generous participation of patients affected with breast cancer, we've been able to get and advance breast cancer therapy in an accelerated pattern over the last several years.

So, I'm excited to see what the next 10 years hold for us where I think we're going to help better screening tools, which will also lead to better preventive tools, and hopefully will significantly impact how the incidence of breast cancer is evolved and have less patients diagnosed with advanced disease.

Host: And Dr. Elkhanany, tell us a little bit more. I'd like it to just tell other providers what you'd like them to know about the exciting genomic assays that are helping the future of breast cancer treatment and what you're doing that they may not know about at UAB.

Dr. Elkhanany: So, I think, genomic assays are a huge topic and I think part of it is, we weren't trained in that in med school about all of these different mutations and cancer biology that underlies them. So, providers read about some of these new, exciting tools and experiment with themselves and send some of these assays and dig into the details and interference behind them, because these are potentially game changers then, as time goes on, they're becoming more and more sophisticated and we see more and more advanced technologies that enter into the assays.

Here at UAB, we have protocols to drive patient care using next generation sequencing within our Precision Oncology Center. We have a multitude of trials targeting specific mutations. And both on a local level, as well as on the national level, including the TAPUR and the NCI-MATCH trial that we call basket trials.

All of these are essentially trying to target patients' individual cancer, both their mutational burden and sometimes even their transcriptomic signatures, like the HRD score to try to infer more personalized treatment options. And a lot of times, and I talk with some patients who come for a second opinion, and say, you know, you've tried the tried and true, which was at some point a clinical trial, so might as both consider a new clinical trial that't been proved that it targets your particular cancer on a smarter line of therapy, if you will.

Host: Thank you so much. And Dr. Rocque, last word to you. I'd like you to speak to other providers about the importance of patient reported outcomes, how you're using them at UAB and how really the patient is the center of their own care when it comes to breast cancer and anything else you'd like to mention.

Dr. Rocque: So, I think Dr. Stringer-Reasor used a good word here and she said personalized and when a patient, woman or man gets diagnosed with breast cancer, it's personal. And so we really need to do everything we can to integrate all of this complex information, the genomics, the clinical trial results, the available data on patient reported outcomes to identify what is the best possible treatment for that individual patient.

And so I think that the patient reported outcomes adds an important level to what we know about these treatments and patient experience. And I would encourage the physicians everywhere to really ask their patients what matters to them so that we can best use the data that is now becoming available from clinical trials and routine care to better support these patients.

And I think, developing in the future, avenues to incorporate these patient reported outcomes into our standard practice and have this just be a part of how we take care of patients, is critically important in the future, because we want to make sure that we're providing the best possible personalized care for our patients.

Host: What a great way to end this fascinating segment. Thank you to all of you for joining us in this round table discussion today. And thank you listeners, for listening to UAB Med Cas. A physician can refer a patient to UAB Medicine by calling the mist line at 1-800-UAB-MIST. You can also visit our website at uabmedicine.org/physician.

That concludes this episode of UAB Med Cast. Please remember to subscribe, rate and review this podcast and all our other UAB Medicine podcasts. I'm Melanie Cole.