Can Nutrition and Exercise Improve Breast Cancer Treatment? The LEANer Study

Inside: Can nutrition during breast cancer treatment affect outcomes and quality of life during treatment? What about physical activity? Research provides strong evidence for the role of nutrition and exercise to reduce risk of cancer. And studies also link healthy lifestyles after cancer with better outcomes for cancer survivors. But little is known about breast cancer and nutrition during treatment and potential to affect treatment outcome.

The Lifestyle, Exercise, and Nutrition Early After Breast Cancer (LEANer) study focused on the impact of nutrition and exercise in women who were newly diagnosed with Stages I through III breast cancer and starting chemotherapy. The goal was to determine if providing nutrition counseling and exercise guidance would result in a higher completion rate of chemotherapy and fewer side effects.

Results did not turn out exactly as expected. However, an unexpected benefit of the lifestyle intervention was unveiled that holds great potential and now needs verification in additional research.

Introducing the LEANer Study of Exercise and Nutrition During Breast Cancer Treatment

The study is a randomized controlled trial that involved women newly diagnosed with breast cancer that had not yet spread to distant parts of the body. It was conducted at Yale-New Haven Hospital and the Dana-Farber Cancer Institute.

• All study participants were receiving chemotherapy. Some received “adjuvant chemotherapy” (after surgery) and some received “neoadjuvant chemotherapy” (chemotherapy used to shrink cancer tumors before surgery).
• Half the women were randomly assigned to a nutrition and exercise intervention program, with individual counseling sessions provided periodically throughout chemotherapy.
• Women in the “control group” were assigned to receive care as usually provided. They had access to a dietitian at any time throughout treatment upon referral by their oncologist.

The Lifestyle Intervention

Registered dietitian nutritionists (RDs or RDNs) who were Certified Specialists in Oncology Nutrition led the intervention, teaching diet and exercise strategies developed in previous studies with people at increased risk of diabetes and with cancer survivors. These strategies were presented step-by-step based on research about successful behavior change. And, since study participants were in the midst of chemotherapy, all strategies were discussed in the context of strategies to manage chemotherapy side effects.

Nutrition strategies focused on a plant-forward diet aiming for these goals:

• Vegetables and fruits: five servings or more each day
• Dietary fiber: 25 grams of dietary fiber or more each day
• Added sugars: no more than 30 grams a day
• Red meat: no more than 18 ounces per week
• Highly processed foods: limit consumption
• Alcohol: no more than one standard alcoholic drink per day

Physical activity goals focused on home-based exercise and three aspects of movement:

• Brisk walking for at least 150 minutes each week (or at least 75 minutes of vigorous physical activity)
• Strength-training exercise at least two days each week, with progressively increasing weight and repetitions
• Sedentary time reduction

Here’s Part One of my interview with Maura Harrigan, MS, RDN, CSO.

I’m grateful for the chance to discuss the LEANer study with Maura Harrigan, MS, RDN, CSO. She’s the project manager of both the LEANer study and its LEAN study predecessor at the Yale School of Public Health and Yale Cancer Center. And she’s previously discussed results of her research on risks of some supplements during breast cancer treatment.

Listen as she describes this lifestyle intervention study and the surprising outcomes.

In this video:

• Background and Introduction to the Study – 00:01
• Outcome #1: Completion of chemotherapy (RDI) – 4:00
• Outcome #2: Incidence of chemotherapy side effects – 5:26
• Note on interpretation: Drop-in effect, Selection bias – 6:30
• Diet quality & exercise can improve during chemo despite side effects – 9:44
• Effects on quality of life: Empowerment & Control – 12:00

Results of the LEANer Study’s Primary Outcomes

Researchers conducting this study had hypothesized that women in the intervention group would have fewer side effects and, as a result, would be more likely to complete their full course of chemotherapy.

Backgrounder: Measuring Chemotherapy Completion

In cancer treatment, oncologists develop an individualized chemotherapy plan. But if side effects of chemo become too severe, dose may need to be reduced or a planned treatment delayed to allow for recovery. Reports estimate that, depending on the type of treatment regimen, nearly one in three women with breast cancer experience a reduction or dose delay in chemotherapy.

Completion of full chemotherapy is measured as relative dose intensity (RDI). When chemotherapy is reduced below 85% of what was initially prescribed, success of treatment tends to decrease.

How Exercise and Nutrition During Breast Cancer Treatment Can Affect Completion

Side effects that can lead to reduced RDI include difficulties eating (due to mouth or throat sores, appetite or taste changes, fatigue, or nausea), peripheral neuropathy, infections, and immune or hematological toxicities.

• Adjustments in food choices or preparation can make it easier for people to eat and to get the calories and nutrients they need.
• Strength-training exercise may help counter loss of muscle and reduce fatigue, as long as sufficient nutrients and calories are consumed.
• Walking and strength-training may also help limit chemotherapy-induced peripheral neuropathy, according to some studies.

Results on Chemotherapy Completion and Incidence of Side Effects

The intervention group and the control group both averaged a 93% RDI, indicating that participants received all or nearly all their full prescribed dose. Contrary to the researchers’ hypothesis, the groups did not differ. In part, the lack of difference may be because the control (usual care) group had a high RDI, providing less opportunity for the intervention group to show a difference.

The groups also experienced similar incidence of side effects from their chemotherapy.

Diet and Physical Activity Can Improve During Chemotherapy 

Researchers scored the overall quality of participants’ diets using the Healthy Eating Index (HEI). This scoring system awards a score ranging from 0 to 100 based on an assessment of how someone’s diet aligns with the Dietary Guidelines for Americans.

Nutrition:

• Since this study was testing a lifestyle improvement intervention, researchers recruited participants with room to improve their diets. Still, women in this study began with an average score of about 67, better than the average US adult score of 57.
• Even so, diets at the start of the study were below recommended amounts of vegetables and fruits and dietary fiber.
• Results: Women in the intervention group modestly increased produce and fiber consumption, whereas women in the control group tended to reduce intake of both.

Physical activity:

• Researchers recruited participants with low physical activity. Indeed, women averaged less than a half-hour per week of moderate to vigorous physical activity and few ever participated in strength-training exercise.
• The usual care group participants increased moderate to vigorous physical activity somewhat during the study. But resistance exercise remained basically unchanged.
• Many women in the intervention group increased weekly moderate to vigorous activity by an average of over two hours a week by the end of the study, though many were still not reaching recommended amounts. And most even added in strength-training.

Nutrition During Breast Cancer Treatment: Participants’ Perspective

As Maura Harrigan, MS, RDN, CSO, discusses in the video above, although participants in the intervention group did not report less occurrence of side effects, they reported being better able to work around them, and side effects did not interfere with lifestyle change goals.

Moreover, participants in the intervention group reported an increased sense of control and empowerment. LEANer study researchers are currently working on a full publication of patient-reported outcomes.

Here’s Part Two of my interview with Maura Harrigan, MS, RDN, CSO.

Listen as she describes the unexpected positive results that will now be the basis for follow-up studies.

In this video:

• What is PCR? – 00:01
• PCR results in the LEANer study – 03:00
• Why caution is needed in interpreting these results – 04:10
• What PCR results could signify if confirmed – 05:10

Pathological Complete Response: The Good News on Tumor Response to Treatment

Although the expected improvement in completion rate of the full chemotherapy regimen and incidence of side effects were not seen in this study, the unexpected finding of differences in tumor response to chemo holds tremendous potential.

Background: Pathological Complete Response to Chemotherapy

A pathologist checks samples of tissue removed during cancer surgery. If no invasive cancer cells are found, this is called pathological complete response (PCR) and has been found to predict lower risk of recurrence or mortality. This is also referred to as physiological complete response or pathologic complete remission.

For women in the LEANer study who received pre-surgery chemotherapy (neoadjuvant chemotherapy), researchers documented the PCR.

Results on Pathological Complete Response to Breast Cancer Treatment

LEANer study researchers found that women who received nutrition and exercise support had a higher rate of complete pathological response compared to those who received usual care.

• The intervention group had a 53% rate of complete pathological response, while the usual care group had a 28% rate.
• Greater PCR among women in the intervention group was seen specifically in those with hormone receptor-positive/HER2-negative and triple-negative breast cancers.
• Since the increase in PCR could not be attributed to increase in rates of chemotherapy completion, this suggests that nutrition and exercise may work through independent pathways to fight cancer tumors and make chemotherapy more effective.

“This finding provides an exciting new possibility that nutrition and exercise can influence chemotherapy outcomes through benefits for immune, inflammatory and metabolic pathways, for example,” says Harrigan. However, “Further study is needed since it wasn’t the primary outcome of our study and needs to be confirmed with larger trials.”

How to Talk About the Study and Put Findings in Context

Several factors need to be considered when you’re explaining the results of this study and translating their potential implications for clinical care.

Interpreting Results of the Study

As Maura Harrigan explains in the Part 1 video, the steps taken to develop and implement a randomized controlled study can affect the outcomes and conclusions.

1. Selection bias: Women in this study may have been better prepared than women typically encountered in cancer treatment. The women – including those assigned to usual care – seemed to have a more healthful diet than many Americans. So it’s possible that a lifestyle intervention might make a bigger difference in RDI (completion of full chemotherapy plan) for women starting off with a lower quality diet and with less time and access to develop healthy lifestyle strategies on their own.
2. One type of cancer: Treatment for different types and stages of cancer holds some similarities, but also important differences. It’s possible that similar results could be seen in other cancers and other treatment types, but results of this study can’t be assumed apply to other situations.
3. The intervention was more than a folder of handouts: Women in the intervention group met regularly with registered dietitian nutritionists who specialized in oncology nutrition. The RDNs provided feedback on discoveries participants made as they logged progress on specific goals they set.

LEANer Study vs. Original LEAN study: During vs after breast cancer treatment

The Lifestyle, Exercise and Nutrition (LEAN) study was a randomized trial involving 100 women with stage 0 to 3 breast cancer who had completed cancer treatment at least 3 months and up to 5 years before starting in the study. All participants had a BMI ≥ 25.0 kg/m2 (categorized as having overweight or obesity).

Three groups compared: Women were randomized to in-person counseling, telephone counseling, or usual care (the control group). Groups were compared for changes in weight, body composition and body circumference measures, and serum biomarkers in conjunction with changes in physical activity and diet. The intervention was provided in 11 sessions spread over six months.

• Weight loss was a goal of the interventions: Women in the intervention groups averaged about a 5-6% weight loss in six months. This exceeded the common definition of clinically meaningful weight losses (5% or more). And it was more than the usual care group, which had no clear weight loss.
• Biomarker changes: A biomarker of inflammation (C-reactive protein, hsCRP) decreased 30% (statistically significant) among women randomly assigned to the weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05). – Greater reduction of CRP, and a reduction in another biomarker of inflammation (IL-6) and in fasting insulin, were seen among the women who had at least a 5% weight loss.
• Lifestyle changed, too. Participants in the LEAN intervention groups increased overall diet quality, dietary fiber and fruit and vegetable consumption, and increased physical activity. Those in the usual care group did not. So while a wide body of research suggests that the changes in insulin and biomarkers of inflammation are related to weight loss, it’s possible that the lifestyle changes contributed independently to some degree, as well as through effects on weight loss.

The intervention in the LEAN study provided the basis for the LEANer study intervention, which was modified to help women address side effects encountered during cancer treatment. And whereas weight loss was a goal of the post-treatment LEAN study, weight management – meaning avoiding weight gain during treatment – was a goal in LEANer.

Results of the LEANer study are unlikely to be related to weight, since the intervention and control groups both lost about two pounds during treatment, with no difference between groups.

Translating LEANer Study Results in the Context of Overall Research

In considering how the results of the LEANer study might represent results in the wider population of people with breast cancer, it’s important to consider several points that Harrigan highlighted.

1. Lifestyle interventions during chemotherapy for breast cancer are feasible. The study challenges previously held perceptions and demonstrates the potential for improving diet quality and increasing physical activity in this population. On the other hand, it’s important to remember that for people with other types or stages of cancer, cancer survivor guidelines emphasize that short-term and long-term nutrition priorities may differ.
2. The choice of what to measure plays a crucial role in research. It affects the number of participants needed to be able to see actual changes. Adequately measuring and describing the intervention is vital for other researchers to be able to replicate a study and verify results.
3. Quality of life and patient perceptions of results are important, but difficult to quantify. For results beyond objectively measured “hard outcomes”, qualitative analysis is needed to capture patient-reported outcomes that might otherwise go unnoted.

Results of intervention trials reflect both the effectiveness of the strategies recommended and the effectiveness of the intervention. If an intervention doesn’t produce enough of the right lifestyle changes, or isn’t set up to adequately measure change, don’t make assumptions about the effectiveness of the strategies or recommendations themselves.

Perfection was not the message: Although objectives and strategies provided in the intervention were based on diet and exercise guidelines for overall health and recommendations of the American Institute for Cancer Research, education and individualized goals were set to be practical, achievable, and in context of side effects and life situations women faced.