Mary Parker:
I'm Mary Parker, and welcome to this episode of Eureka's Sounds of Science.
In the last several years of public health research, it has become clear that there is a great disparity in cancer outcomes based on the patient's ethnicity. For example, according to the National Institutes of Health, Black men and women are more likely to die from cancer compared with the average for everyone else, despite having a slightly lower incidence of new cancer cases overall.
To combat this statistic and improve outcomes for patients, researchers like Dr. Lauren E. McCullough are looking into social and biological causes For this disparity. Dr. McCullough is the visiting scientific director for the American Cancer Society, associate professor in the Department of Epidemiology at the Rollins School of Public Health, and a member of the Winship Cancer Institute, and her research focuses on breast cancer and lymphoma. My colleague, Julia Schueler, research director and therapeutic area lead for oncology for Charles River, is also here to help me unpack Lauren's work.
Welcome Lauren and Julia.
Dr. McCullough:
Thank you so much for having me.
Mary Parker:
I'm really excited to talk to you both. Can we start with Lauren? Can we start with your career background? How did you first become interested in oncology?
Dr. McCullough:
Yeah, so honestly, my first interaction in this field and in this space was very personal. My dad was diagnosed with cancer when I was a sophomore in college. Well, actually I was a freshman, spring semester. I was on spring break. And by the time they caught his cancer, it had already metastasized, so he survived only five months. So, my sophomore year he passed away.
Just through that experience and in the short time I spent trying to help him navigate the healthcare system and get to radiation appointments and chemotherapy appointments, I felt like it was incredibly complicated, and there was just so much that we didn't know. We didn't know the right questions to ask.
So, when I returned back to school, I begun to work with community organizations. There was the Vanderbilt students' meeting for the awareness of cancer was the prominent organization I worked with. And really, thinking about cancer's development, its biology, its life course, really piqued my interest and became what I wanted to devote my career to. I went to Meharry School of Medicine to get a master's in public health and continued to work with the Vanderbilt Cancer Center while I was there, and then ultimately went on to pursue my doctorate in postdoctoral fellowship in the area of cancer.
That really is how I found my space. It was really personal and seeing a gap and seeing a need in understanding and really sitting in a lot of classes at Vanderbilt, as a pre-med student, hearing about the biologic intricacies, and looking at cells, and thinking about molecular pathogenesis without ever really talking about the social factors that impact risk and disease progression. I wanted my career to reflect that experience, and so that has led me to the path that I'm on today.
Mary Parker:
It's kind of a tangent, but just out of curiosity, at that time, were there any organizations that were able to help you through the process? Because I know it can be a lot of bureaucracy and a lot of paperwork, which can be extremely hard to deal with, especially when you're dealing with the stress of the actual diagnosis.
Dr. McCullough:
Right. No, there weren't very many, and it was surprising that this information, these resources weren't coming from the providers themselves. And I think there are a lot of barriers in treatment for patients. My dad was a very smart Black man. We lived, ironically, about 12 miles from Emory where I am now on faculty in Winship Cancer Institute, and that is not where he wanted to go.
So, ironically, that is now where I work and I spend my time, and I have to remind my colleagues and those in leadership the value of having a presence in the community. If we don't have a presence in the community, if we're not supporting those communities, then those community members don't feel safe coming to us. So, it really has informed my thinking and my approach in my work, but also how I advise my colleagues and in institution and theirs.
Mary Parker:
Yeah, that makes perfect sense. Julia, over to you. Just to introduce you, same question. How did you get your start in cancer research?
Julia Schueler:
So when I finished my veterinary science exams, I was looking for a Ph.D. position. The main reason was that I wanted to go back to the south of Germany where the weather is much nicer than where I did my exams, and I came across a project that aimed to unravel the reasons for metastatic spread in solid cancer. I was immediately fascinated, and since then I'm trying to develop model systems that mimic cancer as close as possible, and then help support the development of new drugs to develop cures.
Mary Parker:
Okay, I might have to circle back to you on that development of models to mimic cancer and have a whole other podcast just on that.
Julia Schueler:
Okay.
Mary Parker:
So, put a pin in that for me for later.
But Lauren, I read in one of your bios that your research integrates molecular, environmental, and social epidemiology. I'd like to take those one by one. How is breast cancer affected by molecular or genetic considerations?
Dr. McCullough:
Yeah, so cancer is a disease of cells. When cells mutate, go awry, tumors form and they progress. So, whenever we think about cancer, just on its face, you have to think about what's happening at the molecular and cellular level. We know that there are certain genes that are oncogenes, or those are the types of genes that drive cancer cells and progression. And then there are certain genes that we know are tumor suppressor genes. Those are the genes that activate and help to turn off pathways when cells mutate and go awry. So, in thinking about cancer genetics, the natural paradigm is to think about what's happening with those oncogenes or cancer drivers, or tumor suppressor genes, cancer silencers.
Over the last few decades, there's been a large effort to try and identify what we call high-penetrant genes. Those are genes that, one, we know contribute to carcinogenesis or the development of cancer, but also that we know typically have a pretty high prevalence in the population. I think the science has done a really good job of thinking about that. Some of the ones that come to mind and probably are more well-known are things like BRCA 1 and 2, which drive breast cancer and in some ovarian cancers.
We know that there are certain racial and ethnic groups that have higher levels or higher mutations of those particular genes. Those individuals, if they've had genetic testing, are typically recommended for more surveillance, more screening, et cetera. But there's a lot that we still don't know. There are variants of unknown significance that we have seen, and we don't really know how they tie to cancer. That's just the genetic space, the germline and enzymatic mutations.
My research doesn't really focus on that. It's more in the epigenetic space. I tend to teach people who don't have science backgrounds, if you think about your computer, when you buy it, you have your computer, you open it and there's the hardware of your computer. It's what came with your system. You can't do anything about it. You can't change it. That's kind of how I think of the genome, like you're born with it. The epigenome I think of as being more like the software of your system. You can put in that disc or download that file and add a new program. You can update it, change it over time.
As a public health scientist, I really shifted my science from genetics to epigenetics because from a public health perspective, you always want to be able to tell people, "There's an intervention you can do. There's something we can do. Behavior matters." So, to think about the epigenome on top of the genome really provided an avenue to think about chemopreventative measures for cancer. How does exercise and diet change the way genes are expressed? And even how does the environment change the expression of genes?
That's really where my interests are is really in the epigenetics. Those studies really are emerging. We're starting to see how changes in the epigenome impact cancer progression and even starting to see some new therapies that target the epigenome for preventing poor prognosis in cancer.
Mary Parker:
I've never heard that analogy before. That is fantastic. It makes so much sense. I am not a scientist either, so I really appreciate that.
Julia, you mentioned a talk you attended that basically suggested we could have better outcomes for patients if we tailored their treatment to their genetics, and that sounds like what Lauren is driving at. So, Lauren, would you agree with that take? And could you offer a specific example?
Dr. McCullough:
Yeah, so I certainly agree. I think precision medicine is something that we think about a lot. It's not for cancer treatment. It's not a one size fits all. There are certainly differences in response to treatment by person to person, which is probably due to their underlying genetics, so thinking about how we can be more precise in our treatments, I think, is really important. And we've seen that with some of the latest immunotherapies that have come out, specifically for breast cancer, some of the immunotherapies and new drugs that target triple-negative breast cancer, which is one of the more aggressive types. I certainly think that is an important component of thinking about how we treat cancer.
As a health equity researcher, the challenge that I see often is that drugs and guidelines are created based on the research, based on the trials. What we know for certain is that racial and ethnic minorities and minoritized groups are not equitably included in these trials and in this testing.
So, how do we get to precision when we fundamentally lack the ability to test new drugs, new paradigms in racial and ethnically diverse populations? So, on the one ideal we should be doing precision medicine, and treatment should certainly be tailored to their experiences and their genetics. From a practical perspective, how do we get there when we have just so many challenges in our system when it comes to access and health equity?
Mary Parker:
Yeah, absolutely. Julia, have you anything to add to this? I'm also curious about the sort of German angle, if there's any differences in enrollment in clinical trials in Germany compared to the US.
Julia Schueler:
I think we are, in Germany, is even slightly behind. The talk I was referring to was then based on a paper which highlighted the differences in breast cancer incidences depending on ethnicity, and all this work is coming out of the US. I think, in Europe, we are not there yet. Usually Europeans follow the lead from the US in these clinical trials. But what we definitely see is a development in clinical trials towards more diversity in general, not necessarily ethnicity, but more diversity in general to be able to cover the heterogeneity of a patient population. That's for sure.
Mary Parker:
Getting into the environmental angle, can you tell us about the American Cancer Society's VOICES of Black Women study?
Dr. McCullough:
Absolutely. The American Cancer Society has been leading large-scale population studies for at least the last 70 years. This is the fourth generation of these studies following the Cancer Prevention Study-3, which launched in the mid-2010s.
One of the things that has been important about these studies is they really have been informative for a lot of what we know about cancer prevention and control, like the association between physical activity and cancer risk, or that there are 13 obesity-related cancers, and what we know about vitamin D and cancer and nutrition and cancer. These studies have been hugely informative for thinking about how we relate to the public ways to reduce cancer risk.
Now, what is interesting is despite having enrolled close to 2 million participants in these studies over the last several decades, the Black population has not been well represented at about 4% and at the highest. That brings distinct challenges. When we're trying to make public health recommendations, they're supposed to be for all individuals, and we don't know specifically what the barriers are, what the challenges are, what the exposures are in some of these minoritized populations. So, acknowledging this gap, the American Cancer Society knew that we needed to get more specific with these population-based cohorts. VOICES was really born out of that need to understand what's happening with Black women.
We're centered on black women for a number of reasons. Number one, as you stated in your opening, Black people have some of the highest mortality rates of cancer compared to other race and ethnic groups. And for Black women, it is a group that is smart. They're engaged. They're taking ownership of their health as we've seen the transitions in the social media space over the last decade or so. This felt like a really engaged group and an important group to get more information around.
As a population-based cohort, we are looking to enroll 100,000 Black women between the ages of 25 and 55 who reside in the US and have no history of cancer. Because, again, the goal is to understand what these women are exposed to over time that leads to them developing cancer.
As you mentioned in the environmental space, we're thinking about the physical environment. Where do you live? And we can get air pollution and heavy metals and all of those things, but also thinking about the built environment. Do you have sidewalks? Do you have green space? Are you even able to exercise? Asking about diet and physical activity and sleep.
And then, importantly, asking about the things that are uniquely of interest for this group. What are the social interactions of your community? Quality of life? Social support? Community involvement? Experiences of racism and discrimination in all domains of life? All of these things are important for understanding what is driving the higher cancer mortality in this group, but more importantly, what is driving the incidence of these more aggressive cancers among Black women?
Mary Parker:
Well, and they can come from surprising places sometimes. Wasn't there a research study that showed that talcum powder had some effect on cancer incidence?
Dr. McCullough:
Yep, that has been sort of the latest and greatest and has really been a cause for concern and among all women, but specifically in this group. Last year, there was some recent data out of the National Institute of Environmental Health Science on perms and risk of uterine cancer. So, just thinking about the products that we use day to day, we assume and trust that they're safe for us, but often it's not until decades later that we find out that they're not.
So, we have a huge section on our questionnaire asking about personal care products, powder use, deodorant, use makeups, hair dyes, even tattoos, to really understand how are Black women using these products? With what frequency? With what duration? And then hopefully to, over the years, try and better understand what are the implications for cancer risk.
Mary Parker:
Are you still enrolling in the study now?
Dr. McCullough:
We are still enrolling. We just launched last May, so women in the US, cancer-free, between the ages of 25 and 55 who identify as a Black woman, you're eligible. So, most women are actually eligible for this particular study, which will be incredibly informative for cancer prevention in the years to come.
Mary Parker:
And where can they go to enroll?
Dr. McCullough:
If you're interested, you can just go to voices.cancer.org. There you'll find information about the study, information about the study team. There are lots of FAQs. We understand some of the hesitancies in participating in observational research. And as soon as you land on the page, there is a button to say, "Enroll." So we try to make it really straightforward and easy. You can do it all from the comfort of your home, behind your computer, or even on your mobile phone.
Mary Parker:
Excellent. I will put the link to that in our show notes, if anybody would like to check it out. So, it hasn't even been a full year yet, but are there any early takeaways from the study that you can share?
Dr. McCullough:
Yeah, it hasn't been a full year. We did a small pilot at the end of 2023. I think scientifically we don't have takeaways yet. It is still a little too early. We have about 3,000 women enrolled so far, but we have learned a lot about what motivates Black women to participate in research like this, and then also what are the barriers. And even though these are not necessarily hard science takeaways, I think they're informative takeaways as we consider ways to increase engagement in clinical trials and increase participation in medical science.
Women want to trust the research and the researchers behind it. Women want to feel like partners and not that they are just subjects or participants, and women are really compelled to participate in the study because that it may offer answers for not just them, but the future generations, their daughters, their nieces, their grandchildren. Those are some of just the early takeaways around motivation and rationale for participating that I think has huge implications for science as it moves forward.
Mary Parker:
Moving to another section of your research, can you tell me what social epidemiology is and how you're researching cancer outcomes through this lens?
Dr. McCullough:
Yeah, so social epidemiology is a recently emerged area of the field. It really is just trying to understand what are the social contextes that a person experiences that impact their health. The simplest way to think about social epidemiology is to think of it in the context of social determinants of health, and that is thinking about education, capital or income, healthcare access, environment and social interactions as facilitators or inhibitors of optimal health.
In the field, we really are interested in understanding how all of those things work independently and how they interplay to impact people's decisions on seeking healthcare and their healthcare behaviors and also how that impacts their treatment. In the cancer space, it's really thinking about, how does social determinants of health impact a woman from the time she is seeking to get a diagnosis, whether it was by screening or just noticing a suspicious lump, all the way through treatment and then ultimately survivorship.
It really seems like a no-brainer, right?
Mary Parker:
Mm-hmm.
Dr. McCullough:
Like access to transportation, access to good healthcare, having insurance, having capital, all of those things impact health, but it really isn't until we've begun to think about this deeply that we've seen interesting patterns that go counter to what would be a scientific hypothesis.
For example, in breast cancer, my research group at Emory has seen that the biggest black-white differences or disparities in breast cancer, or death, or mortality is among Black women who have access to care, who have high incomes, who have insurance. And when I've presented these results at the NIH and other academic institutions, people are perplexed because it's like, if a woman has access to care, has insurance, has the means, why on earth is she not having the same outcomes as her white counterparts?
I think it leads us to ask new questions. It's not just having the resources, but how does the facility treat you? How does your provider treat you? Are you offered the latest and greatest treatments, or are you assumed to not have access because you show up as a Black woman? It makes us ask questions about environment, and what is the role of environmental exposures early in life that may lead to more progressive, more aggressive tumors?
So, in doing this research that seems like a no-brainer, I think we have hit some walls in our understanding and in really just our working knowledge around what it means to have access, wealth and power, and that those things don't necessarily equate to equitable outcomes for Black women.
Mary Parker:
I've also seen research that patients are less likely to trust doctors who don't look like them, and they're also less likely to be listened to doctors that don't look like them. That could also have some impact on it, if there's not a lot of Black doctors in your area.
Dr. McCullough:
Absolutely.
Mary Parker:
Yeah. Julia, out of curiosity, in Germany, is there any more sort of standardized path once a patient has a diagnosis?
Julia Schueler:
Yeah. In most EU countries, the public healthcare system is strongly based on governmental regulations and also supported by governmental money. However, so the medical centers are forced to make profit, which is contradictory to best patients' care. So, there is also a commercial component in the system even if it's supported by governmental money.
The regulation to follow first- and second-line treatment are very, very thorough, so most cancer patients receive the treatment following the current guidelines, no matter if this is really fitting to their needs or not. The reason for this is that it's most of the time most straightforward for the medical center when it comes to reimbursement for the health insurance companies.
That is contradictory exactly to what we've discussed before, that if we are even not looking at ethnicity, not talking about individuals who might need a true precision medicine treatment and not a first line that was developed based on clinical trials that did not include all patient cohorts or all representative of all patients that suffer from that disease.
Mary Parker:
That's very interesting. Are there any policy interventions, either in the US or Germany, that either of you can think of that might improve patients' outcomes?
Dr. McCullough:
Well, I mean, certainly, in the US, there's a lot of states that have not had Medicaid-Medicare expansion programs, which certainly Georgia is one of them. I think that is helpful because we do know that having insurance, having some sort of nest egg is certainly helpful in getting those treatments and, I think, ensuring that patients are being treated according to guidelines. Here, we use the NCCN guidelines for cancer treatment. Obviously, there are deviations in that, but ensuring at baseline every patient is being offered the treatment that is right for their particular cancer type, I think, would go a long way.
Standardizations around delays in treatment, I think, are important. We know that Black individuals, minority individuals, low income and rural individuals often have delays. And for cancer, time is everything, catching things early, having that surgery on time. Those are just, high level, three things off the top of my head I can think of.
Mary Parker:
And Julia, what about you? Are there any policy changes that people are pushing for in Germany that might improve patient outcomes?
Julia Schueler:
I think the system we are running in Germany is pretty good. What we see is that the system lacks money, and we have to... If we find a way to finance it better, I think it's a pretty good system.
Mary Parker:
I think this next question was added by you, Julia, if you want to go ahead and ask.
Julia Schueler:
When I read through your publication list, I found that across that you have looked into different environmental factors you have evaluated. Do you see across all these different studies across the years, are there some factors that stood out as consistent across different tumor types that have an influence on tumor growth?
Dr. McCullough:
Yeah, so I do think there are consensus with certain things. You mentioned exercise. I think there've been a number of studies that have said the 150 minutes per week of moderate, 75 per week of vigorous is known to reduce risk of cancer. We've seen that in some of our research, but really the large-scale pooling projects that are out of the NCI, I think, have really been helpful in making that guidance.
One of the areas where I've been looking socially and genetically and epigenetically, as you mentioned, is obesity. I started my career in obesity research. I definitely think it is one of the things, the key drivers of what we're seeing in this demographic and really across patients in the US, and then emerging across the globe with the rise in obesity epidemic. Obesity, that is not just a bystander. It's metabolically active and synergistically impacts carcinogenesis. So, that work, to me, is important. I think there's a lot that we know, again, 13 obesity-related cancers, but I think there's still a lot that we don't know.
Some of our more recent work has been looking more not just thinking about total obesity, so overall adiposity or BMI, but what happens when you have fat tissue in the breast for breast cancer? What does that mean? What does that local microenvironment do?
And so trying to get more specific about, when we say obesity or we say overweight, what is it that we mean? Are we talking about fat within organs? Are we talking about the subcutaneous fat that is really just right under the layers of the skin, fat in the central abdomen and how people carry fat and fat depots? I just think that that area of research is we still have a lot to learn, but as a scientist, I put my money on obesity and understanding some of these differences that we see across populations, at least in the US and, in some cases, around the globe.
Julia Schueler:
Super interesting. Thanks a lot. And along those lines, the other question, I was thinking of if, for example, GLP-1 agonists or other compounds that are now in clinical trials and then on the market, do you see a chance to combine this with cancer treatment? For example, after successful first line therapy, that they will be treated with GLP-1 agonists to prevent or even to reduce obesity to reduce the risk of a relapse?
Dr. McCullough:
Yeah. In a ideal world, that's what we would get to. Trying to figure out, pharmacologically, what could be done to mitigate and block some of those pathways that we know are driving cancer, namely the inflammatory and immune response pathways. The specific modulators, thinking about some of the oxidative stress markers, like the GSTs, I can't say those are the right ways to go, with confidence.
What I do think is of interest and an ongoing area of our research team is thinking about what drugs exist on the market right now that could be leveraged in the cancer setting for oncology. So, right now, thinking about statins, it's a low-cost drug. It can be implemented in any community and even implemented in sort of low-resourced areas around the globe, namely for dealing with cholesterol, diabetes, et cetera.
But does that actually help when you're treating a patient for cancer? And so there are some ongoing observational studies, including our own, some trials that are happening, I think in the US and Denmark. Those types of things are the things I start to think about when I think about pharmacologic interventions. What can we do with things that are already on the market, already FDA-approved, and perhaps have a different use? And things that are low-cost.
Julia Schueler:
Yep, yep, makes sense. Thank you.
Mary Parker:
It does make sense, I mean, because I would say that even if GLP-1 agonists were something that would be useful, they are not really available. There's a big backlog of them, and even people that need them for diabetes are having trouble getting them.
Julia Schueler:
Yeah.
Dr. McCullough:
Right.
Mary Parker:
Yeah. Well, thank you so much, both of you, for your insight into this topic. I really encourage anyone who is interested to go check out that website we mentioned earlier, and that is in the show notes. And if you are part of that cohort and are so inclined, please sign up. This sort of data is incredibly important for the scientists, but also for, as you said, future generations. So, I appreciate both of your time and both of your expertise.
Dr. McCullough:
Thank you so much for having me. I really appreciate the opportunity to share and also spreading in the word about VOICES of Black Women.