Jennifer Ligibel, MD, describes the BWEL trial and the possible impact of weight loss intervention for patients with breast cancer.
Jennifer Ligibel, MD
Obesity has long been linked to poor outcomes in various cancers, including breast cancer. Studies have shown that weight can affect a patient’s risk of recurrence and mortality, driving researchers to develop weight loss intervention techniques for this at-risk population.
The Breast Cancer Weight Loss Study (BWEL; NCT02750826) is looking to identify the relationship between obesity and recurrence in breast cancer through a phone-based weight loss intervention program. Each patient will have a health coach who will work with them over a 2-year period, as well as a toolbox of resources to guide them in crafting a lifestyle of proper nutrition and exercise.
This study is currently recruiting participants, and plans to enroll 3200 women from the United States and Canada who have been diagnosed with stage II or III breast cancer, who have completed standard therapy of the treating physician’s choice.
OncLive: Please describe the BWEL trial.
In an interview with OncLive, lead investigator Jennifer Ligibel, MD, senior physician, Susan F. Smith Center for Women’s Cancer at the Dana-Farber Cancer Institute, describes the BWEL trial and the possible impact of weight loss intervention for patients with breast cancer.Ligibel: The BWEL trial is a study that is designed to looked at the impact of a telephone-based weight loss program on the risk of breast cancer recurrence and mortality in overweight and obese women who are diagnosed with breast cancer. The trial is being conducted throughout he National Clinical Trials Network (NCTN) and the National Cancer Institute Community Oncology Research Program. The Canadian [Cancer] Trials group has also joined the effort.
Can you explain the telephone intervention?
The trial will enroll 3200 women from the United States and Canada who have been diagnosed with stage II or III breast cancer that have finished their standard therapy—chemotherapy, radiation, surgery—and then randomize them to a 2-year telephone-based weight loss program or to a usual care control group. The study will look at the impact of the intervention on invasive disease-free survival—so, risk of recurrence distantly and locally, second breast cancer, other new cancer primary, or death from any cause. The study will also look at overall survival and the impact of the intervention on the incidence of things such as heart disease, diabetes, looking at quality of life and weight change of patients on the trial.The weight loss program is a telephone-based program, which is delivered by health coaches. The program is based on other large-scale weight loss programs like the Diabetes Prevention Program, or a study in breast cancer patients called the LISA trial. Each patient is paired with a health coach who works with them through the 2-year time period.
The telephone calls are more frequent at the beginning of the study. Patients will receive weekly calls for the first 12 weeks, then calls every other week for the next year. And then the last phase of the study in the second year of the program is really a maintenance program, so patients will receive calls once a month.
Could you go into a little more detail about the resources that these patients are given?
Our coaches go through a very rigorous training program where we teach them the basic program, and over the past 2 years we have worked to develop intervention materials. We had a group of individuals—people who have led large-scale weight loss trials in heart disease, in diabetes, as well as experts in nutrition and physical activity from within the cancer community—develop a core set of materials and then variations so that the coaches can work with patients to develop a more individualized weight loss program. We have tools that patients will receive to help them achieve their weight loss goals. Fitbit has been a partner of the study, and so patients who are assigned to the weight loss group receive wireless scales to track their weight and activity monitors. Nestlé Health Science has also sponsored the program, and patients who are interested can receive protein meal replacements, which are shakes for breakfast or lunch. We have another group that has donated scales so that patients can weigh their food and know how much they are actually eating. This is one of the things that my patients always say to me: “I eat healthy food, but I can’t lose weight.” So, this study helps people figure out not only is the food you are eating healthy, but how much you are eating, and how many calories you are consuming each day.
What are the endpoints of the study?
Our study uses what is called a toolkit or a toolbox-based approach. So, we are really trying to optimize weight loss for the individual patients. We recognize that the intervention that is successful for 1 patient might be very different for another patient. For example, our study really aims to have about 30% minority enrollment, with 15% of the patients being African-American and 15% being Hispanic. Studies have shown that various cultural geographical populations respond better to interventions that have different content. We are really seeking to individualize the intervention using this toolkit. A patient can join this study if they don’t have an internet connection—they can use print versions of materials. Or, if a patient is really interested in a vegetarian or gluten-free diet, we can easily accommodate that with this trial.The primary endpoint is looking at the impact of the intervention on disease recurrence, which is the invasive disease-free survival. And that is an endpoint that is used in all of our clinical trials, whether it be of a new chemotherapy drug, or adjuvant endocrine therapy. We are using a common endpoint so that our study can be compared to the typical adjuvant study that is done in women with early breast cancer.
Other endpoints include looking at the impact of the intervention on overall survival, incidence of comorbidities, and quality of life. We are really interested in looking at how this invention impacts symptoms. We know, for example, that exercise can be helpful in alleviating aromatase inhibitor—induced join pain. We are interested in seeing what happens to joint pain over the course of this study. We are interested to see if neuropathy is affected by increased physical activity. There are a lot of secondary endpoints in this study.
There is a very robust translational science component. We not only want to be able to study whether this intervention is beneficial—whether weight loss results in improvements in outcomes—but we want to know who does that type of intervention really help? We are collecting serial fasting blood from patients to see what changes when someone loses weight, and does that predict who might do better as a result of this intervention.
We are also collecting tumor [samples] from time of the initial diagnosis to determine whether there are any predictive markers. Perhaps, it is patients that have a lot of insulin receptors in their breast cancer who might do better, or women with higher levels of inflammation. We do not really know that right now, and this study will provide us with the perfect opportunity to better understand the connection between obesity and inactivity and breast cancer risk and outcome.
Is there a target weight loss goal for these participants?
Does the study come to a hard stop after 2 years?
We know that women who are obese who are diagnosed with breast cancer have a 30% higher risk of dying from breast cancer, compared to leaner women, but we do not know why. This study will really provide us with the unique opportunity to figure that out.The target weight loss goal is 10% of baseline body weight over the first year of the study with maintenance of that over the second year. Each patient takes part in the weight loss or control intervention for 2 years. We estimate that it will take about 4 years for us to enroll the patients—about 3200 women in the United States and Canada. We actually have gotten off to a very rapid start and have enrolled about 400 women over the first 7 months since the trial has opened. I think we are really on par to meet that timeline.
Do you have any advice or comments for practicing oncologists who has patients with breast cancer who are overweight?
We will follow all of the women up to 10 years, so we will be able to look at not only early relapses, but some of the later relapses that often recur in our patients with hormone receptor—positive cancers.The American Society of Clinical Oncology (ASCO) has been really interested in figuring out how to educate oncology providers and patients about the connections between weight and breast cancer, as well as other cancers. There are similar relationships between obesity and poor outcomes in colorectal cancer, prostate cancer, endometrial cancer. So, there has been a lot of effort on the part of ASCO to think about how do we best inform patients and providers and get providers to think about how we talk about these topics with patients.
There are materials that we developed that were released about 3 years ago that are available on the ASCO website about how to talk about this with your patients. Some of the important things are not using terms like overweight or obesity. Sometimes those terms do not really resonate with patients, but talking more about BMI and really focusing on nutrition and physical activity does—which are the things that are really important when you think about helping people lose weight.
How does the enrollment process work?
We do not want people to feel in any way, shape, or form that they were responsible for causing their cancer. We know a lot of cancers recur, and obesity is 1 risk factor—but there are many others. But, I do think that some of this can be very empowering for patients. My patients came to me for years after they finished their treatment saying, “Dr Ligibel, what can I do to help myself?" I didn’t have anything to tell people other than, “Make sure to get your mammogram, take your tamoxifen.” Now, hopefully, for the first time we’ll really have some concrete evidence that there are things that people can do to help themselves. I think that is why we are so excited to conduct this trial and getting the results, so that, hopefully, we can show that there are things people can do to not only help themselves feel better, we know that exercising more and taking care of yourself has a lot of quality-of-life benefits, but we really hope to be able to show that those things make a difference in the risk of cancer recurrence and mortality, as well.This study is being conducted through the NCTN network. We have more than 900 sites across the United States that are participating in the trial. Patients enroll through their local sites, and their study doctor is their doctor at their personal center. From the center’s perspective, this study is no different than conducting a chemotherapy or endocrine therapy trial. They enroll patients, they collect data, they follow the patients over time to see if their cancer recurs, but all of the lifestyle pieces are done centrally.
We then work with the patients on the weight loss program, we send patients in the education group all of the materials—the sites aren’t responsible for that, but the patient still works with their site to have their weight taken, blood drawn, all of other measures of the study collected. These are cooperative group studies that include community and academic doctors across the country.