Dr. Elizabeth Wellberg, Assistant Professor, University of Colorado School of Medicine’s Department of Pathology, Komen Scholar
Obesity affects more than 35 percent of women in the Unites States. Dr. Liz Welberg’s groundbreaking new study, funded by Susan G. Komen, found that women with obesity are more likely to experience a recurrence of breast cancer once their treatment is complete and they may respond to treatment differently.
“What we are really trying to do is to figure out what it is about the situation of obesity. Is it the inflammation, is it the actual process of gaining weight? Is it high glucose? We know that obesity in itself is related to breast cancer but we really still don’t know how.”~ Dr. Liz Wellberg on the questions her team is addressing in her new study
Hosted by Suzanne Stone
A proven leader in building long term community partnership opportunities, Suzanne Stone brings innovative ideas to support Komen Greater CETX’s mission in fighting breast cancer. Stone has gained experience in outreach and education, volunteer programs, donor development and fundraising over her professional career. Stone earned her Bachelor of Science degree in Radio, Television and Film from Texas Christian university and is certified in non-profit management. During her free time, she enjoys going to the beach to catch waves on her surfboard, paddle boarding and watching baseball games.
Dr. Wellberg: [00:04] It’s not enough to just say obesity as a global statement to explain breast cancer. What we’re really trying to do is figure out what it is about the situation of obesity. Is it the inflammation? Is it the actual process of gaining weight? Is it high glucose? We know that obesity in health is related to breast cancer, but we really still don’t know exactly how.
Suzanne: [00:24] Health and wellness a term used so often today it’s almost one word, health, and wellness. You can find workouts and tips almost everywhere you look from Pinterest to YouTube, everyone is a guru on what works best to get rid of those love handles and an extra five pounds. Air quotes. Well, we all know what we need to do to live healthy and we all know that staying in our ideal weight range is important. I don’t know that many of us have really considered how that extra weight can impact breast cancer care. With just a few studies ever done on this topic. Dr. Liz Wellberg decided she needed to know the answer.
[01:08] I’m Suzanne Stone and this is The More Than Pink podcast. Dr. Wellberg is an assistant professor in the University of Colorado School of Medicine’s department of pathology. She’s also a Komen scholar. In fact, donations to Susan G Komen funded her most recent groundbreaking research that connects obesity to the chances of breast cancer coming back. There is a lot of information out there about obesity, but there really isn’t a whole lot of research that has been done around its impact on breast cancer so I’m really curious, Dr. Wellberg, what made you connect these two?
[01:49] Well, I have always had an interest in breast cancer specifically since I started school basically and that’s really because of my mom being a breast cancer survivor, but the work with obesity I started to realize that that was important a couple of years into my training when I actually was working on a group project with some endocrinology experts. And I realized that obesity itself as a disease is very prevalent and it’s becoming more prevalent, especially in women and in children, and so there have been some human studies where they’ve linked associations between excess body weight and the risk for breast cancer. And so I worked with a team of scientists to develop a model system that we could use to study that further and we found some really exciting things.
Suzanne: [02:51] Well, that’s definitely what we want to talk about today and I’m so glad that you’re here because we hear all the time we’re supposed to be healthy and we’re not supposed to be overweight and we’re supposed to make good choices. I don’t know that I would have thought that obesity had an impact on breast cancer, so how does it impact breast cancer? Is it causing breast cancer?
Dr Wellberg: [03:14] So that’s a good question so I can’t answer that question specifically, but we do know that breast cancer is one of these diseases in women in particular that emerges in a situation such as hormone changes like after menopause and breast cancer is associated with inflammation and there’s evidence that changes in your metabolism can actually influence breast cancer growth, and so if you think about obesity as a clinical condition itself, obesity is associated with all of those things. Low-grade inflammation, changes, and disruptions in your hormone signaling and changes in your metabolism so it seems reasonable to think that an environment where all of those things are disrupted in the same situation would actually promote the growth of breast cancer.
Suzanne: [04:13] Absolutely. I can only think as a woman who’s going through menopause, well that’s just like the trifecta right there.
Dr. Wellberg: [04:23] It is, that’s exactly right and our focus specifically on what we call the menopausal transition, which it takes a while for women. It can be I think it’s defined as a year basically of time that women can spend or more transitioning through menopause and during that time lots of things are changing and metabolism is changing. Hormones are not being produced by ovaries anymore, but are instead being produced primarily by fat tissue, for example, and tissues become less sensitive to insulin and some women have trouble controlling their blood sugar during and after menopause.
[05:01] So yeah, that is actually the specific environment that we’re focused on as one of the really strong driving environments for tumor progression in the context of obesity, and something that’s important to point out you said earlier people are made to feel like, Oh my gosh, I should be healthier. I shouldn’t gain weight or I should exercise and all of that, and yes all of those things are true. We should do all those good things, but I feel like it’s not enough to just say obesity as a global statement or broad statement or broad sweeping brush or whatever is enough to explain breast cancer.
[05:41] So what we’re really trying to do is figure out what it is about the situation of obesity. Is it the inflammation? Is it the actual process of gaining weight? Is it high glucose or high sugar in your blood? So really we know that obesity in its health is related to breast cancer, but we really still don’t know exactly how. But we do know that the menopausal transition is a period of time that’s pretty tumor promotional.
Suzanne: [06:07] So that’s really interesting that it really comes down to not just about gaining weight, it’s not just about the fact that when you turn fifty-two or whatever that magical age for you is that you somehow put on ten pounds just by waking up. What happened here? And then all of these other changes that go along with it, but it’s all of these little factors put together that kind of create this maybe magical Petri dish.
Dr. Wellberg: [06:38] Exactly, yeah. It’s a very, we say tumor promotional environment and so one of the things that we’re interested in studying is each of those things individually. So theoretically if all of those components are required for tumors to grow we should be able to interfere with really just like one or two of them and improve breast cancer risk, and breast cancer prognosis and that’s really important because with obesity being so common, it’s easy to just command people, you need to lose weight and not really elaborate on that. Or tell people how or when or why or anything like that and then it can be really frustrating. So the members of our group are really sensitive to that and patients and we want to know if we can do a little bit better.
Suzanne: [07:28] So let’s talk about the details that you and your team have really worked on. So I know one of those is diabetes. You mentioned that maybe insulin, the challenge around insulin as we get older as women. What kind of impact do you see from a diabetes standpoint? I know several breast cancer survivors who have diabetes now.
Dr. Wellberg: [07:49] Oh, okay so that’s a really, really great question. So one of the main sort of overarching hypotheses of my research program is centered on what I call this vicious cycle which surrounds obesity and diabetes and breast cancer. And of course on one end of that cycle is the effect that obesity and diabetes has on breast cancer risk and response to therapy, which is what I just published a paper on and I can talk more about that in a second. But the other side of the cycle is actually the potential risk for diabetes in women who have been treated for breast cancer and if you think about this as a circle going around and around it seems like, obviously diabetes in itself is, is a disease that nobody wants to have to deal with so that on its own is a problem in breast cancer survivors, but then that could theoretically contribute to recurrence of cancer itself.
[08:48] And so what we’re looking at is really focusing on the estrogen receptor-positive subtype of breast cancer and the drugs that are used to treat that, which those drugs that are used are really good drugs and they’ve saved millions of lives, and not all of them cause trouble metabolically but there are some situations when some of those drugs can actually change a woman’s metabolism such that later in life she’s at a risk for developing diabetes. So we are in the process of studying that in animal models, mouse models, and identifying the specific effects of these drugs on tissues other than the cancer. So we’re looking at the liver, we’re looking at the muscle and the fat tissue and the pancreas, even in a very peripheral study, and looking at all of the ways that cancer drugs influence the entire patient if you will, or the whole body.
Suzanne: [09:43] So that’s really interesting, so what you’re saying is that a woman gets breast cancer. She’s got ER-positive breast cancer. She has gone through menopause so she’s already got that. She’s using a drug and I don’t know which one specifically.
Dr. Wellberg: [09:59] There’s a few, yeah.
Suzanne: [09:59] Sure, so she’s taking a drug that has this other effect, the side effect of perhaps weight gain or some sort of metabolism side effect, which makes diabetes more possible for her. She gets diabetes and now suddenly her risk for recurrence has just gone up.
Dr. Wellberg: [10:24] Well, and so that’s the theory.
Suzanne: [10:26] That’s the theory.
Dr. Wellberg: [10:27] Yeah, if you put together all the studies on risk factors, so to turn into a super scientist for just a second, there has never been a study done that has followed a group of patients through that entire progression, if that makes sense. Like followed them from first diagnosis to treatment, to diabetes development, to recurrence that complete study in one in one setup has not been done. But that’s my hypothesis based on observations from multiple studies showing a risk for diabetes in some breast cancer survivors and then, of course, a risk for breast cancer, relapse in people who have diabetes. So, yeah, and like I said the drugs that are used for breast cancer are good drugs and not using those drugs is not an option.
Suzanne: [11:18] Right.
Dr. Wellberg: [11:18] In my opinion, and so I mean my own mother took those drugs and she’s alive thirty-four years later so I think that they’re really good.
Suzanne: [11:26] Fantastic.
Dr. Wellberg: [11:26] But I think that we can do a good job potentially of knowing who is at risk for diabetes and why. And then offering some sort of intervention that would be aimed at being given like during her treatment so that she would lower her risk later for diabetes
Suzanne: [11:47] So you mentioned that you’re using animal models now to look at some of those different things. Tell us about how you’re using that and what are you looking at in these mice that are similar to humans?
Dr. Wellberg: [12:02] Well, so a lot of people do cancer studies in mice. You know that’s not a new thing and a lot of people do obesity studies in mice. That’s not a new thing, but what we’ve done for the most recent study that we published is we used a mouse model of obesity that was induced by a diet that’s high fat and high sugar. I say it’s kind of like cookie dough because the fat is actually butter. So it’s probably pretty delicious and so it’s a diet-induced model of obesity, but two things that we’ve done with our studies that we think are really exciting is number one, we’re using what’s called Thermo neutrality.
[12:43] And so that concept is basically based on the idea that all species, all living creatures have a zone of temperature at which their body functions optimally, and the temperature at which the human body functions optimally and is most comfortable is slightly different than that of a mouse. It’s actually a little cooler. Humans prefer to be a little cooler than mice and so I mean you can expect or you can see why studies on mice are done at temperatures that are comfortable for humans because humans do the studies. But we found that if we increased the temperatures of their cages by just three degrees or so that was enough to really make their metabolism changed to the point that they gained a lot of extra weight the way that we would see in some breast cancer patients.
[13:42] And so the other kind of innovative step that we’ve taken with this model is partnered with clinical oncologists and other breast cancer researchers to take what we call patient-derived xenograft tumors, so those are PDX’s is a phrase that gets thrown around the breast cancer community. These tumor tissues are actually kind of leftover tissues from patients who consent to donate any extra tissue for research purposes. These patients come to the clinic, they have surgery, the doctor does their diagnosis and all of the procedures their doctor needs to do and then the extra tissue is given to the researcher. So we can actually get human tumors and grow them in these mice and we can get a hold of the most common subtype of human tumor, which is the estrogen receptor-positive sub-type. And the benefit to using this approach is that subtype because a lot of times when you do studies in mice and you’re relying on the mice themselves to get cancer, mouse cancer, they don’t make the estrogen receptor the way humans do.
[14:45] So you can’t really study a kind of cancer that represents like 70% of all cases, so that’s what we’ve done, is like I said a diet-induced model. We house the animals within their Thermo neutral zone so that all of their systems are functioning perfectly or optimally like humans and we study the most common subtype of breast cancer, especially that’s common to obesity.
Suzanne: [15:15] Well, I’d like to be a mouse only to try the cookie dough.
Dr. Wellberg: [15:22] The cookie dough, yeah I know.
Suzanne: [15:22] But that’s really fascinating to be able to put a human tumor inside a mouse and then be able to effectively study what their environment and their metabolism does to that tumor.
Dr. Wellberg: [15:37] Right, yeah and so that’s what we’ve done. You know I mean there are a lot of things going on in the environment of obesity. We focused specifically on a pathway like a growth factor pathway that we studied that seems to be activated in the fat tissue, but that’s probably not the only thing going on and the good news is now we have this model system and we have all of these tumors that we can really start to figure out how obesity makes cancer different.
Suzanne: [16:11] So let’s go to that, let’s talk a little bit more about that growth factor signaling for us non-scientists out there. What does that mean?
Dr. Wellberg: [16:21] Excuse me, so growth factors are little proteins that are produced by all the cells in your body and there are there are hundreds of them, thousands of them and what they’re designed to do is basically help your cell grow normally because your body’s always making new cells. Cells are always dividing. Tissues or always kind of regenerating. Your wounds heal, stuff like that. Your infections get killed off and anyway so these growth factors are normal and what we studied is the ones that are specifically produced by the fat tissue that surrounds the breast tumor, and we know from some population-based studies that weight gain in the context of obesity and metabolic disease, which is like high glucose and high insulin, high sugar and high insulin, we know that those things are really important for breast cancer.
[17:19] So within our model, our mouse model system, we focused on the period of time when the animals were actually gaining weight and in the context of obesity and high sugar and insulin okay, so that was the environment and we found that the fat tissue in those circumstances is producing growth factors. And if you think about it, that actually makes sense because when you are gaining weight, your fat tissue is growing and so it’s designed to produce these little proteins to signal from one cell to another to grow and divide and make new blood vessels and just basically grow that’s what they do.
[18:02] The problem is if there are cancer cells there that can also use that growth factor. So that’s what we found is that during this process of weight gain and growth of the fat tissue, basically, the cancer cells that were there, even though we took away estrogen-like you would in the clinic, they just went ahead and used the growth factors and they couldn’t have cared less that we took away the estrogen. So then we were able to block that growth factor pathway using specific drugs and that made the cells then die after we took away estrogen.
Suzanne: [18:41] Wow.
Dr. Wellberg: [18:42] Yeah, so we were pretty excited about that. So what we’re thinking is now is this a pathway that we can really focus on in patients who have obesity specifically and that’s one of the things that we’re interested in finding out. And another thing that we’re interested in looking at is there a way to prevent the fat tissue from making those growth factors under certain conditions, because what was really interesting is this fat tissue in people, we had some clinical samples in there to, but in people who gained weight who were obese but who did not have metabolic disease, their tissue did not make the growth factors. So there’s something about the metabolic disease combined with the weight gain combined with obesity that’s really a bad environment and so that’s sort of our next step is to figure out how the fat tissue is different in that context.
Suzanne: [19:41] So it’s not just about being obese, that itself is not the trigger at least from what you’ve found, but instead there have to be multiple things going on that cause those fat tissues, those fat cells and everything to grow, not just the fat cells but the tumor cells as well.
Dr. Wellberg: [20:03] Right, yeah, that’s what we think. That’s what we think. We think that it’s just not simple enough to use BMI, the body mass index, which is where you get like the normal weight, overweight, obese classification. That’s a good start, but that does not give us enough information because within those categories there are going to be differences in metabolism. There are going to be differences in weight gain and there are going to be other differences that we don’t even probably know about yet.
Suzanne: [20:30] Right, because a woman may be obese at thirty-two and not undergoing those metabolism changes that she might be undergoing at fifty-two.
Dr. Wellberg: [20:39] Exactly, that’s exactly right and coincidentally, this estrogen receptor-positive breast cancer subtype is not promoted with obesity in women who are not menopausal. So there’s definitely something beyond simple classification of obesity and so we’re just trying to make our system better and more like the human condition so that we can really begin to dissect out these pathways and figure out what we can target and when we can target it and who is our target population.
Suzanne: [21:16] Your research absolutely has big implications on the current patient population when you talk about recurrence, but then also on those women who have not been diagnosed yet or who do not have breast cancer yet, but perhaps live in that high-risk category.
Dr. Wellberg: [21:36] Right, yeah that’s true and so what we know from a lot of different studies, both inpatients and in animal models is that weight loss is a great idea. If you can achieve weight loss, for example, a lot of people ask, “Well, I’ve already gained weight, is it too late?” No, it’s definitely not too late. Losing weight or exercising or improving your metabolism through diet and exercise those things all improve things that we know are associated with breast cancer, such as inflammation, lowers your blood glucose and can even in some cases lower your hormone levels that would contribute to breast cancer growth. So I mean there’s a lot of research going into weight loss right now and how do we achieve it? How do we sustain it? And almost everything that we’ve seen so far suggest that it’s beneficial. Even if you’ve already gained weight, it’s still beneficial to try to lose it.
Suzanne: [22:50] So what about women who have already been diagnosed with breast cancer, they’ve already gone through breast cancer treatments, so now they are in that survivorship stage and they are post-menopausal and they are carrying an extra thirty or forty pounds. What does treatment look like or continued treatment, right, because they’re using those drugs still likely, as your mom did? How does that affect them?
Dr. Wellberg: [23:20] Well, and so what I think about when I think of that population of people who is in the window of their cancer kind of gone away, they’re still on the treatments, but during this post-menopausal period I really think it’s important for people to continue to try to live a healthy lifestyle during their treatment and one of the things that I’m trying to figure out and I’m not a not a doctor, I’m not a physician, so I can’t make recommendations along those lines but what I’m trying to use my models to figure out is do we need to be monitoring people like doing a blood test for hemoglobin A1C or some kind of fasting glucose test or doing some kind of measure of people’s metabolism and monitoring their body weight changes or their body composition changes, perhaps more importantly, during their breast cancer treatment as a way of identifying those patients who may be at risk for complications later on. So we have a program here at the University of Colorado for all cancer patients, not just breast cancer patients where they can go over to our wellness center and actually get with a personal trainer and dietitians and go through a pretty comprehensive diet and exercise program while they’re on treatment.
Suzanne: [24:41] Which would ultimately, according to your work and some common sense, but definitely according to your work and the studies that you’ve done will impact potentially whether or not that breast cancer comes back.
Dr. Wellberg: [24:55] Yeah, I would guess that it would, that would be my prediction, yeah, and at the very least it’ll likely impact their development of other diseases like diabetes.
Suzanne: [25:06] Which is another factor for the Petri dish.
Dr. Wellberg: [25:08] Exactly. Exactly. It all goes together and this is why we have to use these somewhat complex model systems, really that incorporate a lot of variables and put them all together and then begin to piece them out in ways that we can only do in the model system. Can’t really do it in people and you certainly can’t do it in isolated cells in a dish. We got to use these animal systems and it’s really beneficial and I think we’re making a lot of progress.
Suzanne: [25:39] It sounds like you’re making tons of progress. I will tell you one of the things I love about my job is getting to raise money so that twenty-five cents of every dollar, if we have donors listening, right, twenty-five cents of every dollar that we raise goes to fund research like yours, because some of the money that we raised funded this research.
Dr. Wellberg: [26:03] It did, that’s right and I am grateful, yeah. Oh, this study wouldn’t have been published without my Komen funding, 100% yeah.
Suzanne: [26:12] It’s a pretty impactful thing.
Dr. Wellberg: [26:13] It’s very impactful.
Suzanne: [26:13] And we can’t thank our donors enough for that.
Dr. Wellberg: [26:18] That’s right, thank you.
Suzanne: [26:18] Absolutely. So tell us what the next steps are. I mean, we’ve talked a lot about your great hypotheses and where you and your team at the University of Colorado are headed, what are those next steps for you and for somebody who’s a patient or a patient advocate or just somebody who is a part of somebody’s breast cancer journey. What can they do to help impact a study like clinical trials or what next?
[26:46] Well so I have this problem of having like a hundred things that I want to do next so I think that for me, the next big thing that I want to do is I want to really get some literature out there that really shows that we can study this risk for diabetes after breast cancer treatment I want to get that out there because that I think that has the potential to make a really big impact because right now is when women who are currently or about to go on treatment can start just being monitored in specific ways to monitor their metabolism. And I think doctors or physicians are definitely aware of changes that go on around a woman’s body when she’s undergoing cancer treatments, but I think it’s really important that patients right now who are going through treatment or those women who are about to start treatment, just pay attention to how your body feels.
[27:43] I mean the idea for my project for this diabetes project actually came from my patient advocate. Her name is Sabrina and she and I were having coffee one day and she said she felt like her metabolism changed dramatically when she was taking Tamoxifen, which is one of the drugs that is given to women with ER-positive breast cancer, and she said she wasn’t the only one that felt that way. And so I just want to encourage people that just because your doctor hasn’t talked to you about something, we just may not know yet about things that are going on and so if you feel strange, it feels like something’s changing in your body, talk to your doctor. And as long as you’re healthy enough for exercise it can’t hurt to exercise and to try to maintain a healthy weight during your treatment.
Suzanne: [28:33] It’s easy to assume that health and wellness is a choice. Dr. Wellberg’s study tells us that for breast cancer patients, that may not be totally true, but we each hold the power to make a choice every day to positively impact our future. The difference is in the details and we must continue to look at the trees to see how that forest was built.
[29:02] A big thank you to Whole Logic for making each and every podcast possible. We record our podcast at the iHeart Media Studios on South Congress in the amazing city of Austin. We couldn’t do it without you guys. Thanks, Mike our studio technician for putting all of the pieces together and making us sound great. To our Komen Austin team who make everything happen behind the scenes and, of course, to our donors who save lives every day by investing in the work that we do.
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About the More Than Pink Podcast
The More Than Pink Podcast is designed to give listeners an insight on what is happening in the field of breast cancer research, treatment, screening and survivorship. Through each episode, experts in various fields share their knowledge directly with you through guided conversations on a variety of topics. If you have any questions, or comments, please email us at firstname.lastname@example.org.
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