ASCO 2019: The BWEL Study: Diet and Exercise in Women Diagnosed With Breast Cancer

This podcast is made possible by the generous support of Lilly Oncology.

Jamie DePolo: Hello, and welcome to the Breastcancer.org podcast. I’m Jamie DePolo, senior editor of Breastcancer.org. We’re on location at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago. My guest is Dr. Jennifer Ligibel, associate professor of medicine at Harvard Medical School, who treats breast cancer at the Dana-Farber Cancer Institute. Dr. Ligibel’s research looks at the relationship between diet and exercise in breast cancer risk and prognosis. Her current project is the BWEL study, which we’re going to talk about in this podcast.

So yesterday at the conference, Dr. Ligibel presented information in the BWEL study, and it’s looking at the connections between exercise, sleep, diet, weight management, and health and wellness outcomes in women being treated for breast cancer. Dr. Ligibel, welcome to the podcast.

Jennifer Ligibel: Thank you so much.

Jamie DePolo: So, to start, let’s talk about the BWEL study. Can you tell us how it came about, where the progress is so far, what you’re doing with it?

Jennifer Ligibel: Sure. Absolutely. So, we know from very large studies that observe women, that weight at the time that a woman is diagnosed with breast cancer is linked to her risk of recurrence and her ultimate survival rates from breast cancer. There have been now more than a hundred studies that have shown that when women are heavier when they’re diagnosed, they seem to have a higher risk of recurrence and mortality from breast cancer. And so what we wanted to figure out is can we change that by helping women to lose weight after they’ve been diagnosed with breast cancer?

So, the BWEL trial is also called the Breast Cancer Weight Loss trial, is a large trial. It will enroll more than 3,000 women across the United States and Canada and look at the impact, the effect, of a weight loss program in these women. So, women are randomly assigned to one of two groups. One group gets a health education program with information about nutrition and physical activity, and then the other group gets that program plus a coach to help them lose weight through a 2-year, telephone-based weight loss program where the patients work with the coach over the phone on topics about diet and exercise. So, the goal is to get people to consume fewer calories, to eat a healthier diet, and to exercise more.

Jamie DePolo: Okay, and the women in the study have been diagnosed with early-stage disease? Is that correct, no metastatic?

Jennifer Ligibel: Yes. So, this is a study that is aimed at women with stage II and III breast cancer. We had to choose a more limited overall group of women with breast cancer because the study… You know, the wonderful thing about breast cancer is that so many women are diagnosed with stage I breast cancer, and the survival rates from that are phenomenal. Ninety-eight percent of people at 5 years are still doing really well, and that’s terrific. We would like to bring the other stages up to that level as well, and so that’s why the study is limited to women with stage II and III disease, where there’s a little bit higher risk of recurrence.

Jamie DePolo: And it is just women? No men?

Jennifer Ligibel: It is just women. There is some emerging evidence that weight may also be important in men, but it’s not very well established. And so we really wanted to start with the very first trial that’s ever looked at the impact of a weight loss program on recurrence in breast cancer with the group that seemed to be at most risk by virtue of their weight. This is also the reason that the study enrolls women with estrogen- and progesterone-receptor-positive cancers and triple-negative cancers, but not HER2-positive cancers, because there’s not as much evidence that weight is important in that group. I think a healthy lifestyle is important regardless of what kind of breast cancer you have, but we’re really trying to follow where the evidence is in this trial that’s trying to test a very new form of breast cancer treatment in terms of its effect on recurrence.

Jamie DePolo: Okay. Excellent. I noticed in your presentation yesterday that you said you had enrolled women from every state except from Wyoming. So, if we have somebody out there listening in Wyoming, how could that person get involved with the study? Does she have to talk to her doctor? Does her doctor have to talk to you? How does that work?

Jennifer Ligibel: Thank you for that question. We really want the study to be as representative of all the women who are treated in the United States and Canada as we are able. And so we were very, very excited when the day after the study opened, the first patient came on to the study, and within the first year, we had about 40 different states with patients in them. Two and a half years in, we have all of the states, even Alaska and Hawaii, other than Wyoming.

So, the way that the study works is that it is open at more than 1,000 oncology clinics across the United States and about 20 in Canada. And so for a woman to participate, she needs to talk to her doctor. She can also go to the ClinicalTrials.gov website where there is a list of all of the clinics that are participating, and she can see if there’s a clinic close to her house.

Jamie DePolo: And I assume there are clinics in Wyoming, it’s just that nobody’s enrolled yet?

Jennifer Ligibel: Yes, there are some clinics in Wyoming. Wyoming is actually also a state where women sometimes get their care in other states. I think this is something that has been a big theme of this ASCO meeting is rural cancer care and sort of how difficult it can be. And so this is one of the reasons, honestly, why we would really love to see every state represented, is we want to show that this program works not only if you live in a big city right next to a cancer center, but if you live in a less-served area, that this is still a program that’s accessible to you.

Jamie DePolo: Okay. Now I think some people may be confused. I know I’m a little confused. There’s been a lot of media coverage about the latest analysis from the Women’s Health Initiative trial. So, it seems like there are other studies that have looked at some interventions, like a low-fat diet. I asked Dr. Chlebowski this morning about exercise. He said that’s a later analysis. So, if you could just explain how the BWEL trial is different from this earlier research?

Jennifer Ligibel: Sure. Well, the Women’s Health Initiative has definitely very much been in the news lately. That was a study actually that was designed to look at whether eating a low-fat diet reduced the risk of developing breast cancer in the first place. It was a very big study. They enrolled almost 50,000 postmenopausal women who had not had breast or other cancers, and they randomly assigned them to a diet that was designed to lower their fat intake or to a usual diet. So, it was not a weight loss study. It didn’t involve exercise. It wasn’t looking at calorie restriction, but really just focused on fat.

When that study was designed, really people in the nutrition community thought that lowering fat was the key to a healthy diet. We’ve learned so much since that point about good fat and bad fat. There’s a lot of theories that trying to cut fat is one of the things that led to so many people becoming overweight and obese in the United States. People ate more processed foods, more carbohydrates, so I think it’s a really complicated situation. The study started so long ago. But that study was designed to look at whether eating this diet would reduce the risk of getting breast cancer. Unfortunately, it didn’t, but they have followed women who got breast cancer while they were on the study over time, and they have found that there may be some differences in how people do after they develop breast cancer. The part that’s a little tricky is that only about 7% of the women on the study got breast cancer, which is good, but in general there wasn’t a health benefit of the program. It was only for the women who got breast cancer.

So, if we could predict who would get breast cancer and tell them to make changes, I think that would be great, and there is ongoing research to tell better who might get breast cancer, but we’re not there yet. So I think that… I struggle a little bit with what’s the public health message from that, but I think I take from that, that this is another piece of evidence suggesting that a healthy diet, taking care of yourself, exercising, potentially, not part of that study, but that these are really important overall goals for people, not only from a diabetes and a heart disease perspective, but probably also related to their risk of breast cancer and cancer outcomes.

So, I think the studies that have been done before — and there have also been two studies that enrolled breast cancer survivors like BWEL, and both of those studies also focused on lowering fat. They were designed around the same time as the Women’s Health Initiative. That was the WINS study and the WHEL study. They came up with different outcomes. The WHEL study showed no benefit of changing your diet, whereas the WINS study suggested that really just for women with estrogen-negative cancer, there was a benefit.

So I think it’s kind of hard to know how to put those studies together, but I think it’s important to recognize they all just focused on fat or, you know, some of them had a little bit more on the diet, but none of them were weight loss and none involved exercise. And that’s I think really the difference with BWEL is it’s a more comprehensive lifestyle program. And it just enrolls people who have already had cancer, which is different than the Women’s Health Initiative.

Jamie DePolo: Okay, and there’s no restriction in the BWEL study. I believe in part of one of those studies that the women had to be overweight to begin with and then they were looking... No?

Jennifer Ligibel: No. So in BWEL, you have to have a body mass index of at least 27, which is in the middle of the overweight range. In none of the diet studies, there was not a weight requirement in any of those studies. Two of the studies did have a requirement that you had to consume at least a certain amount of your calories as fat because they were trying to lower it. One of the studies didn’t have any diet criteria. They kind of felt like you could always have a better diet, which is probably true, but no. So BWEL is the only one of those studies that have actually had an eligibility requirement that you have some weight to lose.

Jamie DePolo: Okay, and there’s no age restrictions, in the study — anyone, any woman who’s been diagnosed with those particular types of breast cancer?

Jennifer Ligibel: You have to be at least 18. Hopefully there are not a lot of younger women, but yes, it’s both pre- and postmenopausal women, which is different than the Women’s Health Initiative was only postmenopausal women.

Jamie DePolo: Okay. Okay. Thank you. Now yesterday, I was tweeting about your session, and we know that obesity is linked to breast cancer recurrence. So that kind of suggests that potentially, losing weight could reduce the risk of recurrence. I know that…

Jennifer Ligibel: That’s what we’re trying to figure out, right.

Jamie DePolo: Right, but I immediately got a reply from someone who’s being treated right now, saying, “That’s great, but a side effect of my treatment…” and I’m assuming, I don’t know this for sure, that she’s probably had some sort of hormonal therapy long-term, so a side effect has been weight gain. So, if you could talk a little bit about that and how women can address that and maybe how you’re accounting for that in your study as well.

Jennifer Ligibel: So, I think this is really a very critical issue. And you know, one of the reasons, honestly, as a medical oncologist I became interested in this because we would tell women, “You should lose weight, you should exercise more, you should eat a different kind of diet,” and yet a lot of the treatments that we gave to people made it hard to exercise. People are tired, they get neuropathy, they can’t feel their feet, they have bone pain that… you know, chemotherapy, women, especially younger women, tend to gain weight, and it was so counterintuitive. We’re telling people do this, and yet we make it hard to do that.

So I think this is one of the reasons that something like the BWEL study is important not only to show “does this make a difference,” but to also figure out how do we help people make these changes. You know, I used to see patients at one of our satellite clinics, and I’d always talk about how important nutrition, physical activity were. And when I stopped seeing patients there and one of my colleagues did, one of the patients commented, “We really miss Dr. Ligibel, but it’s so nice not having to lie about exercise anymore.” And it just really brought home to me that these aren’t easy things. We can’t just tell people to do them. We really need to provide the support to help people make these changes. And so that’s one of the really important pieces, I feel, about the BWEL study is to figure out the how. How do we help people make these changes? And then hopefully, if this study shows benefits, how do we help people afford this? Because right now, you’re on your own to make these changes, and we can tell people, “Sure, join this commercial program or join a gym.” That costs a lot of money, and a lot of times when you’ve gone through cancer treatment, you don’t have a lot of money to spend for these things.

So, I would really love to see these kinds of programs be a part of cancer care. Like if you have a heart attack, you go to cardiac rehab. We don’t have that for breast cancer, and I’m really hopeful that that’s one of the long-term outcomes of studies like BWEL, is that we’ll be able to provide the support to people to make these changes.

Jamie DePolo: Okay. Okay. That’s great, and, too, you mentioned, you know, people join a gym or whatever. A lot of times some people who’ve had surgery or whatever, they may have restrictions of what they can do, and so if you’re not working with an experienced trainer who knows about breast cancer treatment, there could be issues that way, too. So, I’m just… you know, it gets very tricky.

Jennifer Ligibel: It’s tricky. It definitely is. Walking’s always good, but, you know, I think that is… People don’t know what’s safe and what’s not safe, and I think when it comes to diet, goodness, there are so many contradictory things that you read in the newspaper. One of the things we really want for everybody in the BWEL trial, regardless of what group they’re in, is to get more evidence-based information about what is a healthy diet, what is good exercise, what that I read about is real and what… When something happens in a yeast or a mouse and gets a headline, and people start to think they should apply it to themselves, it can create real problems especially because you can read two things that seem to directly contradict each other. So, I think we really need to get good evidence-based information to people about what they can be doing to help themselves.

Jamie DePolo: Okay, and last question. Women who may be in treatment, that’s very draining emotionally, physically, and they’re told, “Okay, you need to change your diet. You need to lose weight. You need to exercise more.” It can be very overwhelming. If someone said, “I can do one of those,” is there someplace you would recommend somebody start? Like maybe… I don’t know. Is it diet? Is that good, or is it maybe just walking a half an hour more per day, or… if someone said, “I can only do one thing,” where would you tell them to start?

Jennifer Ligibel: So, I think it kind of depends on where they are in their treatment trajectory. So, for me, for people that are just starting treatment, what I tell them is staying active is probably the most helpful thing they can do. And it’s so counter to what we used to tell people. “You’re getting chemotherapy, you should rest.” I never tell people that now, because we see that being inactive during treatment is one of the biggest predictors of gaining weight and it contributes to fatigue, and you lose a lot of muscle mass. So, if I’m seeing a patient who’s starting therapy, I always tell them, “The most important thing that you can do for yourself is keep walking.” If you usually run and you don’t feel like you can do that, walk. Even if you don’t usually walk, try to go around the block a couple times a day. Start small, but if you can keep yourself active through therapy, you’re going to be much better off than if you spend 6 months on the couch and then are trying to get back to where you were. It can be really hard.

For somebody’s who post-treatment and really wants to tackle weight gain or they’re starting to gain weight, I focus on diet, because there is no doubt that diet is what drives your weight more than anything else. Exercise can help you keep weight off, but if you don’t change your diet, you won’t lose weight.

Jamie DePolo: Okay. So, then it’s actually losing the weight, not necessarily the body composition, or is that something…?

Jennifer Ligibel: That is something that is a really excellent question, and BWEL will provide a little bit of information from that but not a lot. It’s a hard thing to measure body composition in 3,000 women, but there are some really nice studies, smaller studies going on really looking at how some of these types of exercise especially can help prevent loss of lean muscle. A lot of times when people get chemotherapy, they lose their muscle and they gain fat. So even if their weight doesn’t change, their body composition does. And so that’s another thing that really needs to be kind of explored and we don’t know as much about the connections between body composition and breast cancer.

Jamie DePolo: Thank you very much. I appreciate your insights.

Jennifer Ligibel: You’re welcome. Thanks for your time.