De-Escalation, Genomics and Multidisciplinary Care Redefines Breast Cancer Treatment

Click the play button to listen now:

Subscribe: Apple Podcasts | Amazon Music | Spotify | iHeart Radio

Dr. Dan Simon: Hello, everyone. This is your science at U. H. Host Dr. Dan Simon. Today, I am happy to be joined by three very special guests, Dr. Alberto Montero, Dr. Amanda Amin, and Dr. Janice Lyons. Welcome.

Dr. Janice Lyons: Thank you.

Dr. Amanda Amin: Thank you.

Dr. Alberto Montero: Great to be here.

Dr. Dan Simon: Dr. Montero is the Clinical Director of the Breast Cancer Medical Oncology program and Diana Hyland Chair for Breast Cancer at University Hospital, Seidman Cancer, and Associate Professor of Medicine at Case Western Reserve University. Dr. Amin is the co-Director of the Breast Cancer program and the section Chief of Breast Surgery and the Nancy and Donald Maltby Master Clinician in Breast Health at University Hospitals Seidman Cancer Center and co-Director of the Breast program at University Hospitals Cleveland Medical Center. Dr. Lyons is the Medical Director of Radiation Oncology Regional Network and the Director of Breast Cancer Services, and the Bob and Anne Gillespie, Master Clinician Oncology at University Hospitals Seidman Cancer Center. We're really very fortunate to have these three experts with us today. Before we begin, I thought it might be nice to go around the horn and just have us tell us a little bit about yourself. How did you get into medicine? How did you come to University Hospitals into your specialty area? Why don't we start with you, Alberto?\

Dr. Alberto Montero: Sure. I came into medicine accidentally. So, I actually wanted to be a philosophy professor. I was very interested in ethical issues and biomedical ethics. But my parents didn't think that was a great idea. They connected me with a physician at University of Miami who was doing work for the homeless and really blew my mind, and that threw me into medicine. I did not intend to go into medicine.

Dr. Dan Simon: How did you get into this breast cancer space?

Dr. Alberto Montero: Cancer is always very personal. For me, really, my maternal grandmother was very close to when I was in college and making this change, she was diagnosed with breast cancer. I spent time with her, and she had a mastectomy, lymph node dissection, chemo, radiation. So, I sort of saw what she went through. I was really inspired by her medical oncologist who was really a compassionate person, and so that really piqued my interest.

Dr. Dan Simon: That's great. Amanda, a surgical oncologist. Tell us a little bit about your journey.

Dr. Amanda Amin: Yes. I don't have any physicians in my family, but I decided at a pretty young age, after dissecting some animals in fifth grade, that I was going to be a surgeon. So it wasn't just medicine, it was I was going to be a surgeon, and I felt like that was one of the hardest things that I could do, which was also interesting to me. So, challenge is something that has really driven my career path. When I did my general surgery residency, I had the opportunity to spend a lot of time in the cancer space, and so really just fell in love with the opportunity for taking care of women. So, I think women taking care of women is something that's really special. Our breast cancer patients are definitely a unique population. We end up spending a lot of time with them over their life and survivorship, which is, I think, an important aspect of my journey is really seeing the effects of the care that I've delivered and seeing them really thrive and live their best lives after their cancer journey.

Dr. Dan Simon: That's very inspiring. Janice.

Dr. Janice Lyons: So similar to Alberto, I think it was sort of an accidental path. I was a math major as an undergrad and had accepted a job in the business field and was going to go to school and become an actuary. But I had taken just enough science classes, and I thought, well, let's apply to medical school and see what happens. And then I got in and that was, now, what do I do? Do I turn down this job and pay a lot of money to go to school again? My dad always was my wisdom source. He said, “well, try it. If you don't like it, the job will always be there.” So, I went, but because I didn't really focus on science in undergrad and hadn't really taken the classes that everyone else did, there was a lot of questions as to whether or not I should really be there. But my dad, again, was like, “well, so just try it and see what happens.” And so, my third year of medical school, my grandmother was pretty sick but didn't tell anyone and she was living in Palm Springs, California, the radiation oncology mecca of the country. And my mother, who was a second-grade teacher, said, “Janice, I really can't take off work, but could you just go out and take care of your grandmother?” And certainly, medical school is an easy-going place that allows you just to change everything in the middle so somehow, I convinced the dean of the medical school to let me do an oncology rotation out in California. I was fortunate to spend two weeks doing medical oncology a week in the basement in radiation oncology, and a week with a breast surgeon. When I found radiation oncology, there was just no turning back, and so here I am.

Dr. Dan Simon: Yeah, that's a tremendous story. We're going to talk about breast cancer today. I think for our listeners, it's important to understand that about one in eight women will develop breast cancer in their lifetime. So, the lifetime risk is about 13%. It's certainly, and I don't think there's a family that isn't affected…in my own family - my mother and my sister have breast cancer, and so it's been an interesting journey for our family as well. I think one of the things that would be great for us to start out with - is maybe you could just Set the listeners here straight on what are the current modes of therapy in breast cancer? I mean, people think of chemotherapy, surgery, radiation, maybe just an overview so we can get everyone on the same page before we get to this concept of potentially de-escalating therapies.

Dr. Amanda Amin: What we like to emphasize when patients see us in the surgery space is that surgery is not the only treatment modality for breast cancer. In fact, I am humbled It's enough to say surgery does not cure your breast cancer. It's very important that we consider all the modalities for you to have the best outcome for your cancer. So, frequently, patients start with a surgical excision, and then if they need chemotherapy, that would follow. And if they need radiation, that follows chemotherapy and then for our patients that need hormone-blocking medication because their cancer is sensitive to hormones, that's the maintenance therapy at the end is typically my statement - remembering that each of those are incredibly important to their care.

Dr. Alberto Montero: Dr. Amin, I too am humble and usually, I say that in medical oncology, we can't cure your cancer, you have to have surgery first. So, it's interesting. So, I think on the medical oncology side, we give drugs that have a systemic effect. So, there's a couple of reasons why we do that. So sometimes we give chemo or biologics before surgery to shrink the tumor. But not only that, but how well you respond for the triple negative, which is about 20% of breast cancers or HER2-positive breast cancer, which is also around 20%, how well you respond tells us something about the prognosis. So, when people get chemo or HER2 therapy before surgery, and then they have surgery, and then the pathologist says there's no residual cancer, they have more than a 90% chance of cure. So that's really important. That's one of the reasons we give systemic therapy. But on the other end is, say somebody has curable breast cancer, they've had surgery and radiation, to lower the risk of a recurrence because we're treating the possibility there could be cells floating around that we can't detect. We give out chemotherapy, helps, anti-estrogen therapy, if you have HER2-positive breast cancer, we do HER2 therapy. We give immunotherapy with triple-negative breast cancer. So, depending on the type of breast cancer, the treatment changes, but the overarching goal really is to treat micrometastatic disease that we know is there, but we can't detect it. The risk of having micrometastatic disease sort of depends on the size, the grade, the stage. We can calculate what is the probability of a recurrence, and then we can estimate, we can work back and estimate what impact each of these different systemic therapies can have and improving the chance of cure.

Dr. Dan Simon: Well, that's very helpful to set the stage for this concept now of de-escalation of therapies. Maybe Janice, you could lead off. I remember when my mother had a lumpectomy in radiation, she had radiation for six weeks. So. tell us about this concept of hypofractionation and how therapies might be de-escalated.

Dr. Janice Lyons: When I trained, it was very typical for patients to get six weeks of radiation. I would say that's very uncommon now. Probably the most people get is four weeks of radiation, and there are some schedules now that we can give just a week of radiation. And I think I speak for all of us when I say that de-escalation in care leads to better outcomes, because we know that less treatments result in reduced toxicity from physical, emotional, as well as financial standpoint. And I think of all of us look for opportunities to de-escalate treatment to provide better care for our patients.

Dr. Dan Simon: Perhaps, Alberto, you could talk a little bit about our concepts of medical oncology, of moving from chemotherapy, so we think of hair loss, lot of side effects, to now hormonal therapy or receptor targeted therapies or immunotherapies. Talk to us a little bit about that.

Dr. Alberto Montero: I think it'd be good to start a tie back to why did I go in medical oncology with my grandmother. So, in 1993, she had ER positive breast cancer. At that time, she had lymph node involvement. She had a mastectomy. She had a lymph node dissection. And then she had the more aggressive chemo, the Adriomycin or Ciclophosmab or AC and Paclitaxel. She was postmenopausal at the time. Now, if she would have been diagnosed, now what we would have done is we would have done a genomic test that would determine whether or not she really needed chemotherapy. And if oncotype is one that we use here. So, if the oncotype score was below 25, then we would actually not give her chemo. So now we've gone from a one size fits all. We used to just treat chemo based on size lymph node grade. Again, so we're estimating the probability of recurrence, but what it didn't take into account is the biology. So not everyone has lymph node involvement is going to have a recurrence. Now we have a scenario where we can utilize the expression of certain genes that tell us something about the biology, and then we can tailor treatments and avoid chemotherapy that causes hair loss, nausea. Anthrocyclings can cause permanent heart failure and leukemia. And so now I think instead of a one size fits all approach, we have a more nuanced way. As far as anti-estrogen therapy, we still would treat based on if the tumor expresses estrogen receptors, which is about 50 to 60% of breast cancers. But what's different now is now we have different types of anti-estrogen therapy. We have tamoxifen, we have aromatase inhibitors, but now we can add class of drugs called cyclindependent kinase inhibitors, CDK46 inhibitors, that sort of block one of the important ways that cancer cells become resistant to endocrine therapy. So that's the newest thing with respect to hormone receptor-positive breast cancer.

Dr. Dan Simon: So, Amanda, I think those of us who are in medical school a while ago think of mastectomy and lymph node dissection, and now we've moved to lumpectomy and sentinel node. How did that happen? How did surgery get less extensive?

Dr. Amanda Amin: Yes, it's been quite a journey. We started out with the Hallstead radical mastectomy. So women had their breast, the skin, the underlying pectoralis muscle, and levels one through three lymph nodes dissected. This was horribly disfiguring for women. This had a devastating consequence that went along with it, frequently called lymphedema, which is swelling of the arm. And many of these women had pretty localized disease, no lymph node involvement. And the thought was that the more aggressive we were with our local treatment, the better their outcome was. And yet those women still developed recurrences. They still developed metastatic disease. So, this ties back to my statement about, I don't cure people with surgery. We need all of the different modalities for that best outcome. Bernie Fischer, in the 1970s and 80s, was a pioneer in this concept of a less aggressive surgical approach. He was considered a heretic for a long time in our community because, again, the concept of doing less meant we were probably going to kill women, which was not true. And we have really benefited from his science and the trials that he designed to help us prove that. So, we have randomized trials that demonstrated that lumpectomy or breast conserving surgery or partial mastectomy, or here's several terms referring to that smaller surgery, was not inferior to mastectomy. Unfortunately, there's no trial that was designed to randomize women to receive mastectomy versus breast conservation surgery. No one's going to sign up for a trial like that. We have some recent data, meta-analysis data, comparing all of those trials that looked at breast conservation to mastectomy. It's a recent publication that had over a million and a half women. And we actually were able to demonstrate with that data that breast conservation has a survival advantage over mastectomy. So, we spend a lot of time in our clinic talking women out of more aggressive surgery because, again, it's still a common concept, more aggressive surgery, bilateral mastectomy must give me the best cancer outcome. And while that is appropriate for some women based on their genetic predisposition to cancer or their extent of disease that they, many women, because we are screening so well, are diagnosed with an early-stage breast cancer. And when appropriate, they should know that breast conservation has many advantages for them, not only cosmetically, but now we have survival data to support. So that's management of the breast, which is exciting. De-escalation of management of the axilla is also an important part of their surgical care. Again, every woman had all their lymph nodes removed, regardless of if they had cancer in them historically. We have been slowly de-escalating that intervention. There were several clinical trials that demonstrated that we can do sentinel nodes, which is just removing those first straining lymph nodes of the breast at the time of the breast surgery to assess if there is cancer in lymph nodes or not. Then the women who had cancer had a complete dissection. The women that did not were spared that operation. And then we are continuing to walk this back where we are accepting low burden of tumor in sentinel nodes and depending on our radiation oncology colleagues to manage that local disease and not performing completion dissection in those spaces because radiation actually has a lower risk of lymphedema than the surgical intervention. So, we're continuing to explore opportunities where we can accept low burden of tumor in lymph nodes and not do full lymph node removal.

Dr. Dan Simon: Well, it's really fascinating to hear that very careful clinical trials have helped guide this. Of course, when you swim against the currents. As you mentioned, Dr. Fischer was certainly on the hot seat for a while, but it proved to be right. So, Alberto, there are now multi-omec approaches and molecular profiling that really help us personalize breast cancer treatment beyond traditional receptor status. Tell us a little bit about how you guys are using this. What is the research involved in Seidman right now in these approaches for personalized breast cancer management?

Dr. Alberto Montero: I think at this point, we've been talking a lot about curing breast cancer, so non-metastatic patients, but in the metastatic setting, unfortunately, we can't cure breast cancer, but we can prolong survival. And so really what has led to significantly controlling metastatic breast cancer and improving survival is understanding the biology. So we're at a point now where we can do either in the blood, we can take fragments of DNA and look at the mutations in the tumor, or we can take a direct biopsy of the tumor. And so based on the mutations that are found in the tumor, for example, breast cancer, the most common mutation, breast cancer is PIC3CA, which is a gene that's involved with metabolism. It's an oncogene in a way, and it helps allow the cancer cells to spread and proliferate. And so, we have drugs that are FDA approved that block the PI3 kinase pathway. We also have clinical trials with newer generation mutation-specific PIC3-CA inhibitors. So, we have a new patient. We do a mutation analysis. We look for mutations that we could target, and that usually leads to better outcomes. We have a very active phase one trial. So, for example, we have targeted delivery against HER2 and then have several drugs that are mutation-specific. So, for example, the estrogen receptor is commonly mutated in estrogen-positive breast cancer, and we have drugs that can target the mutated estrogen receptor.

Dr. Dan Simon: So, while it's just exploding, and I guess the best news for patients is that their care and their outcomes are going to improve. Janice, I have a question for you. As an interventional cardiologist, we encounter problems in the coronaries and in the valves in the fields of radiation, and that's especially has been an issue in the remote past on left side of breast cancer. Can you tell us about different modalities, everything from proton therapy versus traditional radiation? How do you make these decisions and how are your fields now safer for patients?

Dr. Janice Lyons: Yeah, I think we realized early on that while mortality from breast cancer was less with radiation, there was an offset with increased cardiac morbidity and mortality. As a field, we needed to adapt to that. So, I think there are a lot of different techniques that we can use to limit the dose of radiation to the heart. And, we use a principle called a tomorrow, which is as low as reasonably achievable when we do that. So, for women with early-stage breast cancer, where we're just treating the breast, oftentimes we treat them prone on their stomach, on a board that allows gravity to pull the breast tissue away from the chest wall. And with that technique, there's almost no radiation to both the lung and the heart, and there's a much less dose to the chest wall, which can limit some of the discomfort that people feel with radiation to the chest wall. That's my go-to, usually, for women who are able to lie prone. Sometimes the position of the heart and the tumor cavity doesn't help, placing them prone. And then we use a breath-hold device that helps inflate the lungs and push the heart away from the radiation field. I'm always surprised at how well the patients are able to do that, no matter what their age and no matter what their pulmonary function. It's just a testament to their will to do what's ever needed to give them the best outcomes. And then we're extremely fortunate to have a proton machine here at University Hospitals, which is the next step in lowering dose to the heart. It's especially helpful when we have patients where we need to treat comprehensive nodal areas, including the internal memory nodes, which sometimes can sit right on the heart. The beauty of the proton beam is it really has a range over which it delivers radiation, and when it gets to the end of that range, it goes away. So we can modulate the way the radiation beam comes in to limit quite significantly the dose of radiation to the heart. And we closed a trial nationally that we were a participant in randomizing patients to protons versus photons with a cardiac endpoint, and we should start getting some early data from that soon. It'll be very exciting to see what comes of it.

Dr. Dan Simon: It's really great to hear that you have new technologies and new ways of delivering radiation that make it safer for patients. So, Amanda, this last question is for you. I think that a lot of women, as you pointed out, have this question that, well, if I have cancer, then a bilateral mastectomy. How do you balance conservation, an oncoplastic result that still leads to a good outcome? When do you recommend if there's a risk for a multicentric disease or if there is a predisposition, a genetic predisposition? How do you balance that with your patient?

Dr. Amanda Amin: Right. This is why we spend a lot of time in clinic going over their options, because that's one of the beautiful things about breast cancer is you get to make shared decisions about treatment. It's not a one size fits all. So, the first thing is understanding their future breast cancer risk, and this is where we get to genetic testing. We follow the NCCN guidelines and make recommendations for patients who have either early age at diagnosis, breast cancer or multiple family members involved, those women meet criteria for genetic testing. When they have genetic testing, though, only about 5 to 10% of those ladies actually test positive for a pathogenic variant that suggests that their future breast cancer risk is also elevated. So, it is uncommon to actually develop a second breast cancer, which is great. And so that helps them understand their risk and can guide our conversations. We do know that women that have pathogenic variants and things like BRCA1 and BRCA2, they have an elevated second cancer risk of around 50, 50 % over their lifetime, which is high. And those women do benefit from having both of their breasts removed if that aligns with their goals. It is not mandatory. There are still women that choose to have breast conservation, and that's an appropriate treatment for their first cancer diagnosis. And we would just follow them carefully for surveillance to make sure we're identifying a second breast cancer if it occurs at its earliest stage. The decision between breast conservation and mastectomy, obviously, women who have extensive disease, often times there's not a choice for them. Multifocal, multi-centric disease, though, when I first trained, that was an indication for mastectomy, and that has changed. We had a recent cooperative group trial that published the oncologic safety of multisight lumpectomies or breast conserving surgery for those women, which is appropriate with low risk of recurrence when they're able to receive appropriate radiation afterwards. So, we spend a lot of time talking through what our expected cosmetic outcome is if we're doing some of those more aggressive breast conserving surgeries, sometimes it is easier to start clean. Removing the breast and doing reconstruction can sometimes give people a better cosmetic outcome. So that's an It's a certain component to this. But we have the benefit of having plastic surgeons who specialize in breast reconstruction. So, when we do a more extensive breast conserving approach, they are able to do local tissue rearrangement, the onchoplastic techniques, and do a reduction and lift on the opposite side for cemeteries. So, we don't have to jump to bilateral mastectomy for our best cosmetic outcome either. In fact, using your own tissue and keeping as much of you actually has cosmetic advantages as well.

Dr. Dan Simon: Well, I'll tell you, it's amazing to listen to the three of you, and I think it's inspiring to hear how this team works together. And I think it's important for our listeners and our patients to understand that this is the reason why you go to a comprehensive cancer center. You get the best of medical oncology, surgical oncology, radiation oncology, plastic surgery support in this space, and it's just amazing.

I want to thank you all for participating today. I know there's going to be a lot more questions, but they'll certainly be able to reach out to you.

To learn more about research at University Hospitals, please visit UHhospitals.org/UHResearch.

Thank you so much, Janice, Amanda and Alberto.

Dr. Janice Lyons: Thank you.

Dr. Amanda Amin: Thank you.

Dr. Alberto Montero: Thank you.

 

The Science@UH Podcast (the Podcast) is intended for informational and educational purposes only. It should not be used as a replacement for medical advice. The statements about devices, drugs, software, or other products may not have been reviewed by the Food and Drug Administration (FDA). The effectiveness of these products may not have been verified by FDA-approved studies. These products are not designed to diagnose, treat, cure, or prevent any disease.  University Hospitals (UH) or a guest on the Podcast may have ownership of licensed intellectual property of this research study.   As such, UH or a guest could receive financial gain from the outcomes of this research. 

The Science@UH Podcast (the Podcast) is intended for informational and educational purposes only. It should not be used as a replacement for medical advice. The statements about devices, drugs, software, or other products may not have been reviewed by the Food and Drug Administration (FDA). The effectiveness of these products may not have been verified by FDA-approved studies. These products are not designed to diagnose, treat, cure, or prevent any disease. University Hospitals (UH) or a guest on the Podcast may have ownership of licensed intellectual property of this research study. As such, UH or a guest could receive financial gain from the outcomes of this research.