Wendy Demark-Wahnefried, PhD,
RD
Professor
Behavioral Science
The
University of Texas, M.D. Anderson Cancer Center
Dr. Demark-Wahnefried: Hi, I'm Wendy Demark-Wahnefried and I'm a professor of Behavioral Science at M.D. Anderson Cancer Center. It's a pleasure to be here today and I'm going to be talking about diet and exercise and the relationship to breast cancer.
As far as the objectives of this talk, I'm going to give a brief overview of the worldwide trends in cancer survivorship, talk a little bit about cancer-related sequelae and how diet and exercise may be important for those, evidence supporting the need for diet and exercise interventions, and then also be able to address those within the context of the guidelines that are set forth by the World Cancer Research Fund.
So, if we look at overall 5-year survival for breast cancer, here are the CONCORD study findings that were reported just a few years ago. And we see here that breast cancer survival is almost at around 80 percent, and for most developed nations, over 80 percent. And this is really good news because it shows that we are winning the war on breast cancer.
And it shows that as far as early detection, our efforts in early detection, our efforts toward improvements and treatment have made an impact, and, indeed, the number of cancer survivors in the world is growing and right now, it's over 25 million, and that's growing really quite rapidly. Breast cancer survivors make up a large portion of that. And as the world increases in age, this is a trend that we're going to see more and more cancer survivors. So, diet and exercise can make a very important impact in this population.
That was the good news about cancer survivors and now I'm gonna talk a little bit about the bad news about cancer survivorship. First of all, as far as breast cancer survivors go, there is a documented higher incidence of depression. And that may be overall, but definitely, in some subgroups of cancer survivors. Secondly, cancer survivors have a higher incidence of fatigue and that is really a real phenomenon in women that have breast cancer. That fatigue cannot only last during the time that they're on active treatment but well into their survivorship years and well over the year after survivorship or after active treatment. And then they also are at risk for functional decline and I think this is worth showing on a graph here.
This is a graph, a study that was done by Hewitt, Rowland, and Yancik, and it really concentrated on older cancer survivors. Those that were over age 65, but since the mean age of breast cancer is 65, this is very relevant. So this graph shows in green, what the risk would be in the general population for functional decline, and in blue, what breast cancer--well, excuse me--what survivors risk is. And what you see here is that cancer survivors have significantly more risk across psychological problems, activities of daily living, physical functioning, and also work-related problems. Those problems, as far as physical functioning though, are very prevalent. So people report that they have problems running to catch a bus, lifting groceries, walking a couple of blocks, walking up the stairs, and this is concerning because we would like to return people to their normal activities.
Continuing down the list of problems that cancer survivors have, picking up after functional decline. You also see that you have--that survivors have increased risk for other cancers, second cancers. For breast cancer, this could be leukemia, it could be a host of other cancers. Cardiovascular disease, diabetes, osteoporosis are major sequelae, major comorbidities. And they also have, are at increased risk for adverse body composition change. This could include osteoporosis, but then also changes in muscle mass versus fat mass, and something that we'll concentrate on a little bit later in this presentation. And lastly, cancer survivors are at increased risk for mortality. And when you compare them against their age and race matched counterparts, they have about a 40 percent greater risk of death than those that are matched to them.
If we look at that mortality, and here's a graph that shows that, perhaps a little bit more completely. Again, cancer survivors are at increased risk of cancer mortality. Here are the data for breast cancer, specifically. And the dark blue bar shows you that overall risk. And then the green bar shows you what the risk is due to their breast cancer progressing. The purple or the light lavender bar shows what the risk is from dying from other causes. And what you see here is that breast cancer survivors are much--are at greater risk from dying of other diseases than their breast cancer--than the breast cancer itself. So, those other diseases primarily are cardiovascular disease and diabetes. And the first study on this was done in the early 1990's by an investigator named Brown who was at the National Cancer Institute in Bethesda. He concludes that article with stating that the evidence that cancer patients die of non-cancer causes at a higher rate than persons in the general population is overwhelming. So these are people that we cure of their cancer, but then they die of other diseases and we have to be very aware of that happening and be aware of prevention. Again, over half of those deaths are due to cardiovascular disease and diabetes.
So what are some potential solutions to those problems that cancer survivors have? Well, diet and exercise. Lifestyle factors can make a big difference, And here is a chart that shows you what contribution, if you look over the literature, what contribution dietary modification can make, and what sort of impact exercise can make. And the number of checks denotes the level of evidence. So, one check here means possible benefit, two checks means probable benefit, and three checks means convincing benefit. And here, what you see is that for depression, both diet and exercise can be helpful, possible benefit. Fatigue, diet and exercise could be important, exercise perhaps more so; same thing for adverse body composition change, functional decline. And as far as comorbid factors, again, diabetes, heart disease, both diet and exercise are heavy hitters. These can make a big difference in whether people will end up dying from other forms of comorbidity. Evidence is very strong, and the evidence is growing as far as recurrent disease or their progressive cancer. So, I'm going to outline that evidence now in this talk ...
and frame that within the World Cancer Fund Diet and Exercise Recommendations. So here are the recommendations that are put forth. I'm just going to go over these really quickly and then we're going to be concentrating on each of these a little bit later on. Weight: be as lean as possible without becoming overweight--underweight. Physical activity: try to get at least 30 minutes of physical activity a day. For breast cancer survivors, we really recommend 150, at least, 150 minutes a week. Dietary patterns: trying to avoid sugary drinks, sources of sugars, sources of fat, and really concentrate on a plant-based diet with little red meat, if any, and whole grains in consumption of at least 5 servings of fruits and vegetables a day. In parts of the world that are less developed, avoidance of salty foods is important for stomach cancers, as well as, aerodigestive types of cancers. Supplements: right now, we are really suggesting that people just get their nutrients from food. And I'll show you the evidence a little bit later on that and why that's important. And then for alcohol: what we recommend particularly for breast cancer is if women do drink, not to drink more than one a day. And really, this is questionable too.
So, let's go into overweight and obesity and their contribution to breast cancer. Well, here you see a bar graph. The green bar shows increased risk for those that are overweight, that means a BMI of 25 to 29.9. And then the blue bar is obesity, so BMI of 30 or greater; so, different amounts of over-nutrition that are supplied here. And the various cancers across the X-axis, you have breast cancer, colon, endometrial, kidney, gall bladder, and gastric cardia. For breast cancer, there is a significantly increased risk for both overweight and obesity in women that develop breast cancer during later in life. So for postmenopausal breast cancer, around a 20 percent increased risk. The thing that you must keep in mind is that this risk is only for those women that develop breast cancer later in life and really does not pertain to women that develop breast cancer early in life, during premenopause. Because, indeed, those women--it's actually women that are lean, that are more at risk for that disease so overweight, is again, a risk factor for breast cancer developing later in life. But you see here, as far as what the--here we have breast cancer compared in magnitude to other cancers. Yes, it is weight-related but perhaps not as weight-related as other cancers like endometrial cancer here. You see that overweight and obesity plays a huge role, same thing for gastric cardia and kidney cancer, also gall bladder cancer; so, significant role, nonetheless, but not as much as other cancers.
Okay, so this graph shows the relationship between obesity at the time of diagnosis and how that may play into increased rate of mortality. And what you see here is for breast cancer. Women who are obese; now, granted a BMI of 40 is pretty obese, but they have a two-fold increase in mortality if, indeed, they are obese at the time of diagnosis.
Here is a graph that shows BMI change after diagnosis. And this study was done with a cohort of women that were diagnosed with breast cancer from the Nurses' Health Study, a study that was done by Kroenke and colleagues in 2005. And the second set of bars there, and just let me orient you to the slide. The pink bar is recurrence. The yellow bar is breast cancer mortality. And the blue bar is all cause mortality. The referent bar is or the reference set of bars, is the second set of bars to your left-hand side, and it shows that women that maintain their weight are the referent here. Those that actually lose weight after diagnosis, it may seem that there is a slight rise in all cause mortality 'cause you see that blue bar a little bit higher for people that lose greater than 0.5 kilograms per meter squared. However, that is not significant. In comparison, however, let me orient you to the bars over to the right-hand side, and that shows that women that have an increased of 0.5 to a 2 unit change in BMI, and those that have a greater than 2 unit change in BMI, have significantly greater risk for all three: recurrence, breast cancer mortality, and all cause mortality. So women should be encouraged after their diagnosis, based on these data, to keep their weight as stable as possible. And just to put this in perspective, as far as what magnitude of change really could impact on their risk, a 0.5 unit change for a woman that's 5 feet tall could be as little as 3 pounds. So we're not talking about a lot of weight change here. Even modest amounts in increase in weight can increase risk for these factors.
So let's talk a little about weight gain after diagnosis of breast cancer because it is a fairly common phenomenon. It is associated with some forms of hormonal therapy like tamoxifen and chemotherapy. And most of the research has focused on people that were treated with chemotherapy. Chemotherapy has shifted overtime, and the earlier studies suggested that women were gaining anywhere from a mean weight gain of 2.5 to 6.2 kilos over the time that they were on treatment. The disturbing thing is that during this period of time which is from the 1990's, 1 out of 4 women gained over 22 pounds or 11 kilos during the time that they were on chemotherapy, which is a lot of weight to gain. The more recent studies, and it could be because oncologists are more aware that weight gain is a problem, and are cautioning their patients to try not, well try to avoid weight gain is 1.4 to 1.7 kilograms during the time of treatment. We see greater gains in women who are African-American or black women, those who are sedentary to begin with, and those with less education. And the very early reports suggested that this weight gain was because women were eating more, and that increase dietary intake was really responsible for this weight gain. But those studies were anecdotal and they weren't well controlled.
And in fact, one of the earlier investigations that my research team did back in the 1990's and the early 2000's was to try to determine what was the cause of that weight gain. And our largest study in this area was a study, it doesn't seem that large, but it is the largest metabolic study to date, is a study on 36 women that got adjuvant chemotherapy, and 17 women that just got localized treatments, surgery plus or minus radiation. And we compared those two groups of women. And what we did is- we looked at dietary intake, we looked at physical activity, we measured metabolic rate. And you see here there's a picture of a woman that is underneath a hood and that's how we measured metabolic rate by indirect calorimetry and we also measured body composition using DXA. And what did we find with these studies? Well, we found that there was no difference in dietary intake, and we found that, in fact, really, the culprit might be decreased physical activity. And that's why we see some of the weight gain that we do, we do see.
The other culprit is this... We see changes in body composition that occur post- diagnosis. And this graph shows in the solid lines, the changes that occur in women that got the adjuvant chemotherapy versus the changes that occurred in the dashed lines of women that just got the localized treatment. And you see the women that got just surgery and radiation, their body composition changes are of far less magnitude. So I would like you to orient yourself to the solid lines. And the green line shows weight gains in fat mass over the one year period post diagnosis. The blue line shows decreases in muscle mass one year past diagnosis. And what you see here is that these women are gaining significant amounts of fat while they're losing muscle. Now, that's a very unique pattern of weight gain and it's called sarcopenic obesity. I am going to go into that in just a second, but I just wanted to say while the slide is on the roster here, is that the changes that occur in these women one year after diagnosis are equivalent to 10 years of normal aging. So these women, in fact, are experiencing accelerated aging.
Okay, so what about sarcopenic obesity? It's a unique pattern of weight gain. Usually when people gain weight, they gain not only fat but they gain muscle. So when women gain weight when they're on chemotherapy, they gain fat, they lose muscle. And so that is very unusual and it does, this sarcopenic obesity, does occur with other sorts of conditions. Again, it does occur with normal aging but the changes that these women are experiencing are far accelerated above any sort of normal aging pattern.
It also--these changes also can occur with prolonged physical activity and certain forms of medical conditions like Cushing's syndrome. So the recommend--what's the recommended therapy? Exercise, strength training exercise to increase that muscle mass, because metabolic rate tracks directly with muscle mass. And hence, if these women are losing lean body mass, they are reducing their energy requirements. And so, over time, they are going to need less energy. And if they are not exercising to bring their muscle mass back up, they will definitely need to eat less than they ever did pre-diagnosis.
So we did a pilot study to determine: Are these adverse body composition changes, a proof of principle study, are they--can we actually hinder them, or are they something that is just going to be a natural phenomenon that occurs with adjuvant chemotherapy? So we did a very small study of 10 women. And we explored if on a strength training, aerobic exercise, lifestyle behavior program, that also included dietary change. So, decreased fat, increased fruits and vegetables, and also, a calcium-rich diet, because these women have osteoporotic concerns. Is that beneficial for them? And these slides show women that are pursuing physical--aerobic physical activity, as well as strength training. Let me say that the most of the muscle mass loss that has occurred is in the lower body region. So this is where we really concentrate our strength training exercises.
This is the graph that I showed you before, the solid line with the green line going up and the blue line going down. The green line being fat mass, the blue line being muscle mass, and what we see when we start intervening with diet and exercise intervention. The dashed line, the dashed green line shows that we actually can have women start to lose fat mass while we're intervening with this intervention. And the dashed line there that's increasing shows that we actually see some increases in muscle mass. So these body composition changes that women that are on adjuvant chemotherapy are experiencing can be hindered; and actually, their body composition can be improved through lifestyle change. So this is really some good news here.
I'm going to now kind of go into exercise and how important that is. The observational study, and here's a graph, a Kaplan-Meier curve that came from the work that Michelle Holmes did, again, on the cohort of people that participated-- or the women that participated in the Nurses' Health Study that developed breast cancer. And what you see here is that the very bottom curve are the women that were --reported more physical activity. And you can see here they have far lesser mortality than those who are only--who are sedentary. There are also several other studies that have shown that fatigue can be abated with physical activity, walking interventions primarily. And then, also, there was a very interesting study that was done by Kerry Courneya and colleagues on 242 women that were receiving adjuvant chemotherapy. And he found that an exercise program actually increased the proportion of women that were able to stay on schedule and stay on their original treatment. So this is very good news and really points to how important physical activity may be.
In addition, there have been some recent findings by Kathryn Schmitz. And one of the big concerns with the breast cancer population is the concern of lymphedema. For years, we've been telling women not to lift weight, to be very careful about how much weight they lift, and that they should avoid it at all costs. Well, what Kathryn Schmitz did, is she took a group of high-risk women, women that actually had been treated for lymphedema and were being followed for lymphedema, and randomized these to a group that got progressive resistance training with a compression garment, and those that were on the control group. And what did she find? Well, she found that there was no difference in arm swelling between the two groups. She also found that the group that received the progressive resistance training had far less self-reported lymphedema. They had far greater lower and upper body strength, and probably most importantly, they had far fewer lymphedema flares. So, this is very encouraging news and points to the fact that we really should be pursuing progressive resistance training in this population.
Okay, dietary pattern: getting into the data regarding the need for a plant-based diet, watching fat, those types of things. Here are some observational data, again, looking at the cohort of women in the Nurses' Health Study. And here, you see women that eat a western diet, the risk-- the point estimates and the 95 percent confidence intervals for women that eat a western diet versus a prudent diet and what impact that may have on cancer-related mortality. What you see is that for cancer-specific mortality, the top graph--the top line under western diet, and the top line under prudent diet, shows that it really doesn't matter if you eat a western diet or you eat a prudent diet as far as breast cancer-specific mortality. However, if you are looking at other cause mortality and that means heart--mortality that occurs with heart disease, diabetes in this population who are at high risk. The western--those that die of other causes that are--let me rephrase that--women that eat western diets are much more likely to die of other causes than women that eat prudent diets. So since death is a fairly strong end point, it would be in line to tell patients to consume a prudent diet that's more plant-based than western-based. This is further supported by data from the WINS study.
Now, the WINS study was a randomized control trial that enrolled postmenopausal women that had early stage breast cancer and randomized them to-- one-third of them got a low-fat diet and were followed for at least 5 years. Two-thirds of them were just counseled on a healthy diet. And what the top row shows is that indeed there is a survival advantage or a, excuse me, a difference in breast cancer events in women that followed the low-fat diet. They had protection than compared to women that didn't follow a low-fat diet. And surprisingly, when this study was conceived, it was thought that the greatest effect would be seen in ER- positive women. Well, the data show that they really-- those are the women that really don't receive that much benefit, but the women that have ER-negative disease really derived the most benefit. And that's important because that's where our chemotherapy tends not to work as well. ER- negative women, particularly triple negative women, are in greater proportion in parts of the world (for example, Saudi Arabia, parts of Africa), have very high percentages of ER- negative women, and a low-fat diet could be very important to this population. Now, these data are compelling. They certainly show the benefit of a low-fat diet but they are confounded. And how they are confounded is that the women that followed the low-fat diet lost significantly more weight. So we don't know if the low-fat diet is important, or the fact that they lost weight that's really the important factor here.
Let me contrast these with findings of another study that was done very close on the heels of the WINS study, and that's the WHEL study. And this study tested whether a plant-- very high plant-based diet, low-fat diet and-- that had 30 grams of fiber and 16 ounces of vegetable juice a day, had any survival advantage in a little bit bigger sample of women, 388. And this study was done not only in postmenopausal breast cancer but also women that had premenopausal disease.
Here are the findings of the WHEL study and you'll note, they are much different than the table that I showed you from the WINS trial. Here, we see as far as breast cancer events, breast cancer deaths, overall deaths, there's no differences between groups. So what's going on here? Well, it could be chance alone that is rearing its head. It could be, again, the fact that women in the WINS trial did lose weight and weight is probably--and weight is most likely the big factor here between the two groups. In WHEL, the women in both groups maintained their weight. And it also could be that the WHEL trial at baseline, these women ate 7.4 servings of fruits and vegetables a day. So, the fact that we did not or-- that study did not screen out women with a high vegetable consumption could have led to these findings. It is noteworthy that the women that did follow the, that were on the WHEL study, those that had higher carotenoid levels at baseline, suggesting that they had a higher fruit and vegetable intake long term, had better survival. So this kind of points to the fact-- or points to the premise that it's the long-term dietary behaviors that we establish that are probably even more important than short-term change.
Supplements: don't use supplements to protect against cancer. And I just want to review some of the literature here because a lot of women, a lot of breast cancer patients have questions in this area.
Soy: many women ask about soy. And there have been three trials that are primarily aimed at reducing hot flashes in women that have breast cancer with soy supplements. All of these trials showed no difference in hot flashes between study arms. Multivitamins: should I take a multivitamin? And as far as women that were undergoing treatment with radiation therapy, there was one trial that randomized women to placebo versus a multivitamin. We found--that trial found that fatigue was significantly different between arms, but surprisingly, was more--the women that were receiving the multivitamin had much more fatigue than the women that had placebo. So, trend in the opposite direction.
A trial that was done by Hayes on L-arginine tended to be a small study in 96 women. There was no difference in response rates. And perhaps really the only trial that we have of a supplement or a functional food that is working, is a trial that was done by Thompson in 2005, using a pre-surgical model for breast cancer, and showed that women that received a flaxseed- supplemented diet in the form of a muffin, had much lower Ki67 rates in their tumor when it was excised than women that didn't, and more apoptosis.
Alcohol: if women drink, the recommendation is to limit to one drink a day. Obviously, if women don't drink, we do not want to be encouraging alcohol. So this recommendation is only for those that are drinkers. Okay, as far as alcohol consumption goes, we see that alcohol is linearly related to primary risk, meaning there is no safe amount of alcohol to drink if women are trying to avoid breast cancer in the first place. If we look at cancer survivors, we, first of all, find that the prevalence of risky drinking is no greater among breast cancer survivors than in the general population. But how does that tie into progressive disease and other forms of cancer? Well, the first study was done by Trentham-Dietz and showed that women that had--that drank actually may have protection against ovarian cancer. However, and then we also see a study by Reding that shows that survival might be increased in women that drink. But those findings are balanced by a more recent study by Li that showed that actually the hazards ratio is increased for contralateral disease over women that are teetotalers. So the news-- the jury is still out as far as alcohol consumption but we do know that moderate alcohol consumption is cardioprotective. So because women with breast cancer are at higher risk, this may be one of the reasons why alcohol may be beneficial.
So, if we look at the lifestyle practices of cancer survivors--, of breast cancer survivors, how do they stack up against these recommendations? Well, we have a population in need here because 60 to 71 percent of breast cancer patients are overweight. 50 to 54 do not eat at least 5 servings of fruits and vegetables a day. The recommendation is not to take supplements, yet 60 to 80 percent of women that have breast cancer take supplements, and 70 percent are sedentary. So there is a lot of work to be done.
Physicians and healthcare providers can make a difference. And here's a slide that shows the teachable moment that occurs after a diagnosis and when women want to get diet and exercise interventions. And you see here that they're most interested in them at diagnosis or soon after. So this is a good time to plant the message.
So, in conclusion, areas for further research or future research is to determine the diet and exercise impact throughout the course of neoplasia; to determine if weight loss can influence cancer risk and cancer progression; and how do we make that weight loss occur? Is it through energy restriction as far as diet, increased exercise, a combination of both, and what is the weighting of both of those? And then to determine what the impact of diet and exercise is now on the five major subtypes of breast cancer that had been identified. And then, finally, and probably most importantly, to determine the best way that we can get women to exercise more and eat a healthier diet. So, with that in mind, I thank you for your attention. And just am really happy to have this opportunity with you.
Diet and Exercise in Breast Cancer video
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