We all know the saying: The apple doesn’t fall far from the tree. As the son of a dentist and nephew of a doctor, it’s no surprise then that Dr. Hy Muss ended up in the medical profession. Nor is his empathetic style of care which seems to emanate from his upbringing as well.
What might have been unexpected, however, was his area of focus. Unexpected because his specialty, geriatric oncology, was in its infancy when Dr. Muss began his career. Thanks to Dr. Muss and others, much has been learned about breast cancer in elderly people—and there’s still much more to uncover.
A BCRF investigator since 2000, Dr. Muss is professor of medicine at the University of North Carolina School of Medicine and director of the Geriatric Oncology Program at the UNC Lineberger Comprehensive Cancer Center. Dr. Muss has devoted his career to breast cancer research—with major interests in both early and late stages of the disease, treatment outcomes, and care for older women with breast cancer. He also has a major interest in biomarkers of aging and how they might predict survival and treatment response.
Chris Riback: Dr. Muss, thank you for joining. I appreciate your time.
Dr. Hy Muss: My pleasure. It’s great to be here.
Chris Riback: I want to get into, of course, your science and approach to care, but in researching you I’ve got to say it became obvious where I had to start. What does it mean to be a real Brooklyn boy? And while they can take the boy out of Brooklyn, you’re, I assume, in North Carolina right now where you work. Doctor, can they ever take the Brooklyn out of the boy?
Dr. Hy Muss: Never, never. So, I’ve lived in North Carolina a long time, but I’ve heard myself being referred to as the guy with the New York accent that’ll take care of you. So, it never leaves. And I’m very proud of it.
Chris Riback: I would imagine that you are.
Dr. Hy Muss: Yes, I’m proud of it.
Chris Riback: Why would they ever want to take the Brooklyn out of the boy?
Dr. Hy Muss: Well, there are people that try to move up in life and don’t want to show their roots. I think more people like me, we’re very proud of where we grew up.
Chris Riback: True.
Dr. Hy Muss: One of the great cities of the world before they built the Brooklyn Bridge. So very proud of it.
Chris Riback: Yes. And the second item that struck me, you may not read your own reviews online and I hope you don’t mind, but I did. And here’s just a little bit of what your patients say. “Dr. Muss is off the charts wonderful!!!! Very empathetic and willing to listen, conveys his compassion for situations in an effective manner. Dr. Muss is outstanding and kind and professional.” “I appreciate Dr. Muss’s warm and kind demeanor so much. He is an exceptional physician. I am grateful he was in charge of my care. He is an amazing man.” Now first, just for the record, you don’t fill those out yourself, correct?
Dr. Hy Muss: I don’t, nor does my mother.
Chris Riback: I understand the desire that she would have to do so, but those obviously are powerful and meaningful. Why are empathy and compassion seemingly as much a part of your approach as is scientific or medical expertise?
Dr. Hy Muss: Well, first, I’m very honored and flattered by the comments. They’re very lovely. Probably my upbringing, my parents were wonderful people. They welcomed everybody. My father was the neighborhood dentist. My uncle was the neighborhood GP. My mother lived in the same neighborhood. And I guess she was the therapist to half the neighborhood people when they had issues, but they were wonderful caring people. And I thought their style and how they lived their lives was important. And there are so many patients we have that are so sick, so afraid.
Most of us know the medicine. We know the statistics of the treatments, et cetera, but trying to get a patient comfortable, getting to know them. I often tell our residents, if you don’t know whether this patient has a dog, you’re not doing your job. And in this frenetic age, I think getting to know people and being kind makes you more effective. They’re more likely to take your advice, to trust you. And so I try to do that and give a little bit of me at the time. My heart’s on my sleeve. I’m a very easy read, but it kind of works for me. It’s not for everybody. And I think that resonates with some patients who are petrified of their diagnosis and want more than the treatment plan.
Chris Riback: Petrified is surely the right word for so many and helping them manage that component of their care. Listening to you is perhaps as much as the science in terms of importance, or certainly close. You may know that you’ve been called a triple threat, excelling in research, education, and the clinic. So let’s talk about the research if we could. I wanted to first understand geriatric oncology. Has that always been your focus and what drew you to it?
Dr. Hy Muss: So, it hasn’t always been my focus. I finished my fellowship a long time ago, 1974. And when I finished fellowship and went into academic oncology, which I’ve been in all my life and which has been just a great career choice for myself, no regrets, we treated all cancer. There weren’t specialists in leukemia and lymphoma. The tools were so marginal. It took a long time to make oncology a specialty. I took the second set of boards and that was because to become a medical specialty, I had to prove you could do things for patients, not just identify a disease. So I was in early, but as things evolved and treatment got better, surgery, radiation, chemotherapy, all the modalities got better, prevention, early diagnosis. You had to specialize to really be an academician, and that’s still true, more and more true today.
And it’s actually happening in the practice situation in the community where docs are taking little niches. So, I did all types of cancer over the years, got into breast cancer and then had the great experience of working with one of probably the planet’s great geriatricians, a guy named Bill Hazard, who’s emeritus professor at Wake Forest, who wrote the first textbook on geriatrics and who try to proselytize all [and] get us interested in geriatrics. So, a long story, but I wrote a paper with one of our residents, Kathy Christman. At that time, she’s a practicing oncologist, on older people treated with metastatic breast cancer. And at that time, many clinical trials excluded older people. They were written right into the criteria, but we did not. I had an incredible boss.
Now you can’t do that. That’s ageism. And this is 30, 40 years ago. Now it’s a popular term. Then no one knew what ageism was, but he did. And so, we included it and we showed that the older people derived similar benefit. They didn’t have profoundly different toxicity and they had the same response rates and survival. So we published that in JAMA. And all of a sudden, I had friends calling me about their mothers, grandmothers, and patients who were older. And I realized, I didn’t really know a lot about them. I wrote this paper, but I didn’t know a lot about caring for older people. And I got interested. I learned a lot. I had the opportunity of working with people nationally, like Harvey Cohen at Duke. We chaired a major committee and slowly morphed into geriatrics, especially when I learned the demographics. Right? So in the elevator, people say, how come you’re interested in that, Hy? And I’ll say, what’s the average age of cancer in the United States? When they watch TV and they see Brian Song and they’ll say 45. No, it’s 67.
So, as we get older, as an aging population, as we get older, your chances of getting cancer rise dramatically with age. And as we get an older population, there are more and more of these patients. And the challenge is they frequently come to your clinic with more than cancer. Now, there are 75-year-old tennis players, and there are 75-year-old people who are quite ill, not from their cancer frequently, but from diabetes, heart disease, and strokes. And the challenge is to sort out these people and identify the problems of the patient and take care of the cancer as well as the patient.
And sometimes the cancer, although the word is profoundly intimidating, is really not the patient’s problem. They can’t walk down the street without falling. So, I’ve slowly gotten interested in this. And as you may be aware, Medicare is a great service, but caring for older people in the United States is extremely difficult. We’re short of physicians, we’re short of geriatricians, et cetera. So, we’ve become interested in this field in trying to improve cancer care in older patients. And it’s a great challenge. And working with older people is a great reward.
Chris Riback: And I know from reading just a little bit about you, I believe that among your questions that you will ask a patient is can you walk to the end of the street or a lot of questions and investigation around mobility and frailty.
Dr. Hy Muss: Sure. I mean, when you take care of a patient today, we’re all specialists and we all have the patient’s records and know about the cancer. And so my style is with older people and with all patients is my first question is after I introduce myself and tell people what I do for a living is to say, tell me about yourself. I tell them, I know about your cancer. Tell me about yourself. What do you like to do? Are you working? Are you retired? Get to know people. And then as part of my evaluation, because that tells you a lot about people.
Chris Riback: Yes. Yes.
Dr. Hy Muss: I do a little what they call a geriatric assessment, which can be very formal, but it’s essentially knowing in an older person, can they care for themselves? Do they pay the bills? Are they a caregiver for their husband or wife, or are someone caring for them? Can they move the chair across the room? Do they have friends and social support? Are they eating enough? Most older people losing weight are not doing it because their cancer is spread. They’re doing it because they’ve lost the joy of eating and don’t have the same appetite. And so all these things come into caring for the older patient and frequently they trump the issues related to the cancer.
And what’s important about it is many of these issues are fixable. So in addition to your treating their breast cancer, which may have an excellent prognosis, you may send them to physical therapy so they don’t have a fall and break their hip and start on a very disastrous road. So geriatric oncology maybe is the consummate form of holistic medicine in that we’ve really got to know that whole patient, because there’s vast differences in health status, income, social support in older people. So you just can’t say she’s 75 and have an image in your mind, which most people do of maybe someone older, because they can be vastly different patients depending on their function, et cetera.
Chris Riback: So, I think I know what aging is, but what is molecular aging?
Dr. Hy Muss: Yes. So, one of the mysteries of biology, of life, is why do we age? Why is people hair going gray? Every organ system in our body, including yourself. I hate to tell you this.
Chris Riback: Only half as much as I hate to hear it.
Dr. Hy Muss: After around 30 or 40 is declining. We’re losing little air sacks in our lungs. Our kidneys can’t filter as much blood. Our liver isn’t efficient at building proteins. Our heart doesn’t pump quite as strongly. We’re losing brain cells. Nothing to be afraid of. We have a lot of reserve, but we slowly lose this. So why does this happen? And one of the things is in our environment, even oxygen causes little damage to a lot of the cells in our body, subtle damage that accumulates. And for instance, take a liver cell. So over the years, the liver cell may be damaged by oxidation, by chemicals coming into it. And what the cell does is it slowly changes to a cell that can’t divide and replenish itself, but it doesn’t die. It’s what we call senescent, the terrible term, because we call some old people senescent. I hate it.
They [the cells] can’t divide, but they don’t die. And they actually make dangerous little chemicals, inflammatory and other proteins that actually can predispose people to cancer. And that may be why cancer is more common as we get older, because we accumulate all these inflammatory and other factors that flow through our circulation all through our body and increase our risk for virtually any type of cancer—[cancer] increases with age, from leukemia, breast cancer, colon cancer, cetera. So biologic aging is this process where cells go from vigorous cells that can divide and replenish organ systems to cells that don’t divide well, but are not dying and make actually bad things for us. And that varies too. But the interest is that may help us predict side effects of drugs, may help us predict in the future who’s likely to be very robust and who’s likely to be frail.
Now we don’t know all of this yet, but it’s a hot area and there’s more and more wonderful scientists in the laboratory, social science, medical care involved in trying to figure out this process. So biologic aging is really real. It’s why we change as humans, but the major causes, can we reverse it? Billion dollar business, looking for drugs to keep us young, right? Fountain of youth. Hence Florida, right? Ponce Deleon. So, we’re still looking and there’s a lot of wonderful laboratory work here too and I would say the focus of people like me is not to make people immortal, that’s not going to happen. That might be a curse, but to live the best life you can for as long as possible in the best health.
Because if everybody lived to 85, it would be much different if people lived to 85 with a great life between 65 and 85 and vigorous and could do things or sitting in a wheelchair watching television all day and not being able to take advantage of life. So, the endpoint might be the same, but the quality of life would be vastly different. So that’s things we’re very, very interested in seeing if we can affect.
Chris Riback: And on the oncology front, how does chemotherapy induce the biological aging that you were just discussing? How does that science work?
Dr. Hy Muss: So, the best example, how do we know that? What’s the best proof? It’s children. So, childhood cancer in this country is one of the great achievements of oncology of cancer care because we’re curing so many children with cancer. Leukemias that took the lives of young children in weeks to months are now cured, but there’s a price that many of these young adolescents and children pay. And that is by the time they’re 35, they actually have the disease spectrum of 65-year-old adults. And it’s not because the cancer is grown back. It’s because they have heart disease. They have developed second cancers different than the first.
And so the mortality rates go up and they have a lot of serious illness and they get frail. And I’ve worked with this with one of my colleagues. That’s the best evidence. And there’s also things like evidence in when we’ve given women chemotherapy and measuring the oxygen, they can take out of their lungs. Like Lance Armstrong took all that oxygen out. He was a great biker. And we found that if you give women chemotherapy that if you have two 65-year-old women and one had chemotherapy and one didn’t, the 65-year-old woman will have the oxygen extraction of really a 75-year-old woman. She’s aged 10 years. And the only explanations we have are the chemotherapy. And then there’s been our work, which couldn’t have been done without BCRF to look at another marker of aging, a gene called p16.
Chris Riback: Yes. I wanted to ask you about the p16 marker.
Dr. Hy Muss: That as we age goes up, the expression of this gene goes up and what it does is it codes for a little chemical that stops our cells from dividing. These changes in the gene, you see are responsible for the organ declines in every organ of the body, whether it’s the kidney or lungs. And it’s probably true from the limited data we have in humans. So we measure this gene whose little protein, little chemical goes up dramatically as we age, makes our cells less able to divide, and we’re measuring them in the immune system.
One of the questions that we talked about earlier before this was, do we know the implications of that? We really don’t. It takes years to see these changes. You treat children with leukemia at ages 5, 10, and 15. You don’t see the changes till they’re 15, 20, or 30. We’re impatient populations. So we don’t know, but we’re very concerned that these changes may result in that 55-year-old women having much more serious illness, comorbidity, diabetes, heart disease, and lung disease, when they’re in their 70s, than a similar woman her age would have who didn’t have chemotherapy or breast cancer or other, and was shown it in other cancers too. So we are very excited about using that as a predictor of side effects and seeing if we can accurately predict certain side effects, could we do interventions ahead of time to prevent them? And probably we can get to it later.
The main one we’re interested in now is what we call peripheral neuropathy. A lot of chemotherapy drugs, taxine drugs, which are widely used in breast cancer, are among the most effective drugs in breast cancer, both in early and late breast cancer, those drugs damage the little nerves that go to our fingers, toes, and can cause numbness, tingling, pain. If it’s very bad, it can affect your ability to walk, open a jar of ketchup, can have a profound [effect]. And it affects a lot of people. And certainly, for certain occupations, it can be terrible. Like if you’re a violinist or seamstress. And so we’ve actually through BCRF help, been able to show we can predict this pretty accurately. And we’ve actually got a National Institute of Health-funded study now to verify it. And so we’re excited as a predictive factor.
And then we’re also looking to see if we can predict other chronic diseases as you age, like what’s your risk of heart disease or diabetes. That’s trickier because we take care of cancer patients and they get out five or 10 years. We discharge them to their family doctors, but we may need to think about following these people much longer over the years to see if there are problems. And if there are, could our research have predicted who will get them? So, studying this gene may open a lot of opportunity to do different things for different people, prevent side effects in the short run, by identifying people at high risk, and using an intervention that may be helpful.
And then in the long run by who’s going to get other serious other diseases of aging. And that’s very important because most women with breast cancer today fortunately are cured [after] their treatment, but we’re treating them very aggressively. And if they get chemotherapy and perhaps lots that they need, large amounts of radiation, et cetera, that may have adverse effects down the road. And so we’re very interested in learning more about that.
Chris Riback: I’m sure that you are. On this point of studying chemotherapy and the effects. So you helped publish in 2009—I think it was in the New England Journal of Medicine—the results of the first chemotherapy trial in older patients with early-stage breast cancer. Now, earlier in this conversation, you discussed how you were at the very beginning stages of I guess geriatric oncology, and that predated this 2009 study. But I was shocked that it took until 2009 before somebody thought to do a chemotherapy trial on older patients with early-stage breast cancer?
Dr. Hy Muss: Yes. Well, our field is very new. I don’t know if there are 100 geriatric oncologists in the United States now. But in the early days of clinical trials, older people were frequently excluded, was a paternalistic approach, which should have never happened, but it did. It was ageism. And people didn’t appreciate the demographics. So there were virtually no trials focused on older people. And a lot of the data that we used were done on younger people, people in their 40s, 50s, maybe early 60s. And so their tolerance of chemotherapy may not have been representative of older people. And so fortunately with the support of my colleagues, Larry Norton, Cliff Hudis, Eric Weiner, great people, the Alliance, Rich, really terrific people, we wrote this study and we published it in 2009, but we started this study in 2000.
Chris Riback: Wow.
Dr. Hy Muss: It was nothing then. And we had to convince the NCI, which were very gracious, good people that it was worth doing. Because if you looked at clinical trials, even if they didn’t have an upper age, they were like two people, 70 and docs wanted know if I give Mary Smith who’s 76 chemotherapy, is it going to be an overwhelming problem for her? So we did this study, it was a national study. It took us a long time to accrue. And we found out that it was a group of women. In retrospect, there probably women who had triple-negative breast cancer who were older, who derived the greatest benefit. At that time, we didn’t know a lot about triple-negative breast cancer, but in retrospect, that’s probably what we showed. There certainly may have been some patients with hormone receptor-positive. There certainly are who derived benefit from chemotherapy, but that was the first seminal study.
And they were all over 65 and we had great support nationally. And we were very proud of it. And in fact, at the recent ASCO meetings is one of the few other studies. Most studies in this area, a lot were started. They weren’t completed. It was hard to randomize people. We had to randomized women to a chemotherapy oral form, a single pill versus IV chemotherapy. So those women were incredible to agree to this. And a lot of other people have tried this and not been as successful, but kudos to our French colleagues, Dr. Etienne Brain, and his group, for just at ASCO now publishing a very large study and kind of showing sadly that at least using the technology they did to select patients, the chemotherapy had little to no benefit when added to the endocrine therapy, to the hormonal like therapy, Tamoxifen in older patients, not a very good study.
There’ll be a lot of discussion. It doesn’t mean there’s no benefit for chemotherapy as a blanket statement in that group of people. But in our study, we included other people. So it was a little different, but it was terrific. And even now, as we speak worldwide, we don’t have more than a handful of studies focused on older people. There are some in leukemia where we know the biology is a lot different than older people than younger, but in breast cancer, colorectal cancer, lung cancers, we just don’t have as much. But people are coming around. The FDA is pushing pharma to include older patients and encourage them on trials. The National Cancer Institute has been wonderful and the National Institute of Aging, but it’s still been very, very hard to do to get these older people on trials. So we’re proud of the trial, but we’d like to see many more of them, but it’s been difficult.
Chris Riback: And that’s what I was going to ask you. What would you really like to know next?
Dr. Hy Muss: Well, I think it’s several things. I think from the tumor biology point of view, we’re learning a lot from people of all ages, but one of my interests is going to be are these biomarkers of aging? There’s a lot of interest in what we call bio clocks. As we age, our little methyl groups, little almost like hydrocarbon groups go onto our DNA and change the way it works and adds to our aging processes and developing other areas. There’s a lot of interest in that. And I think that’s a little bit different. That’s going to be focused on can we predict how certain people will do with certain treatments or without treatment? But I think one of the challenges now is there’s such an explosion of new drugs that affect the immune system, all the new immune inhibitors and all the new, exciting biologic agents.
There were some wonderful news for breast cancer patients from this year’s ASCO on drugs that attack the HER-2 gene, even if it’s not our standard definition—very exciting and wonderful work by Dr. Modi and her colleagues. Then the question is, do we know about older people? Is that 80-year-old person going to do as well? And so, what I’d like to see, and the National Clinical Trials Network, the NCORP [NCI Community Oncology Research Program] people have given support to the large groups to do studies of these drugs specifically in older patients. And it’s not to repeat the response rate, although that’s important because I think it’s going to be pretty similar. It’s to look if the toxicity profiles are different. So, we can make sure that older people on this what appears to be a terrific new drug, trastuzumab-deruxtecan, do older people get more of these lung side effects than younger [people]?
You might have a trial with 1,000 patients in it, but when you parse it out and you get people over 75 and 80, you end up with a handful of people and it’s not good enough to really get a good idea of the confidence you can have in the risk of these side effects. So, I think a lot of the research is going to have to focus on older people who still don’t get on these trials and very little headway, very little headway, and getting more older people on NCI trials and look at the pharma data. The FDA has done a beautiful drug trying to push to do it, but it’s difficult to do it because pharma has developed some great drugs, but no CEO wants to go in on Monday, say, ‘I put a lot of older people on the drug, and they didn’t do too well.’
Chris Riback: No, I’m sure not.
Dr. Hy Muss: Not going to do too well on the Dow that day. So I think we’re going to have to do them and they’re very important and we’re going to have to take the best treatments, not just in breast, but in all the cancers and really focus in on older people. And in breast, a lot of these treatments that we’re doing today, adding these cyclin-dependent kinase inhibitors to preventive therapy, adjuvant therapy, drugs that have not just costs, but monetary costs, but a lot of potential side effects, very little is known about the older patients. And I think we need to focus on carving out trials specifically for those older people.
So, when they come into our office and say you know Dr. Muss, I’m 78. I’m a little shaky on my feet. Is this drug going to have really bad side effects in me that I’ll be able to look that person in the eye and say we’ve studied a group of people like you, and here’s what we found. Yes. It was a little worse, but it may be worth trying it or not a good idea and I think that’s what we need to be focusing on.
Chris Riback: Yes. What a call to action and complicated call to action to generate studies on geriatrics. And I can only imagine you’ve outlined some of the issues. I can only imagine how complicated it is from companies to agencies to support it, to the patients themselves who may be tired and have other things going on and may not feel like participating in a study at 75 or 80 years old is kind of what they should be doing. And I could almost imagine an argument of how meaningful participation in such work could be.
Dr. Hy Muss: Absolutely. We did a study in the old CALGB [Cancer and Leukemia Group B] group. It was one of the first studies we did in geriatrics. And we looked at institutions that were part of the group. And we looked at what trials they had available in their institutions. And these were top-quality academic centers. I’m not going to name them. But when we looked, all these patients were eligible for a clinical trial. But when we looked how many patients were offered it by age, we found out that if you were less than 65, about half the patients were offered it. That’s bad enough because it meant that people were too busy or didn’t think of it or whatever. But when you looked at people 65 and older, it was only 25 or 30 percent.
Dr. Hy Muss: So, there was an intrinsic ageism because all these patients were eligible. And then we said, if you offered the patient the trial, how many accepted? And it was the same for older and younger people. It was about half. So, if you spent the time discussing the trial with the older patient, they were as likely to participate as the younger patient. Now there’s a bias in there. We didn’t offer it to all the patients. But those that we did and there’s been other work like this, and it’s very, very important. And it takes longer to explain things to older people. In this country, older people tend not to have the education of younger people, although we’re so numerically illiterate as a culture. I’m not sure that all matters, but explaining it, people are scared of placebos and it takes time to do it.
And of course, with older people, you’ve got to get their caregiver or family involved. They got to be part of the team. Everybody’s got to be in sync and understand about it. And so we’re working on it, but it’s not like in the United States, we’re getting more and more funds to screen older people and do things. I love to see it, but it’s going to take a while. We need a few more Claude Peppers [in government] and old committee chairman with power to put a lot of money in aging research, but it’s a challenge. And it’s a challenge for all the doctors and nurses and research associates, trying to get these patients on trial, irrespective of the type of cancer. Takes a lot of work. A lot of logistics. Caregivers got to be involved, but we’re not going to give up.
Chris Riback: Understood and quickly to finish out. How would you characterize, what role has BCRF played in your research?
Dr. Hy Muss: Well, BCRF has really been instrumental. We wouldn’t be having this conversation if it weren’t for BCRF. So, I’ve had the continued good fortune of being funded, of knowing the lovely, elegant, amazing Evelyn Lauder, and working with Larry Norton and other people who built this from the ground up. This organization’s philosophy has been to support investigators who have done some things but give them money to do new and exciting things. And I think our research in looking at how the biology of aging affects cancer care and older women with breast cancer, and we’ve looked at side effects and patient-reported outcomes, et cetera, I could never have done it without BCRF. And it has led to some lovely, lovely funded NIH grants. I’ve had the opportunity of working with Ned Sharpless, our prior director, who’s really taught me the biology of aging.
But without the BCRF providing those hard dollars to do these studies because they’re not like drug A, and we’re going to get a new drug that’s going to cure everybody. They’re much more translationally based from the lab to the clinic, than learn about patients and bring it back to the lab. Couldn’t do it without BCRF. And so they’ve enabled us to do this, to look at new little nuances with continued funding to build on these studies. And I think in our case, we’ve been able to get federal and other grants to actually leverage their wonderful support, but it wouldn’t be possible. Wouldn’t be possible.
Chris Riback: Dr. Muss, thank you. Thank you for your time. Thank you for what you do with patients, both those that are your patients and those who are not every day.
Dr. Hy Muss: Well, it’s my pleasure to have been here to discuss this. Thanks for asking me. And as always, I appreciate the BCRF support and interest in what we’re doing. Thank you so much.
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