Exploring the Feasibility, Acceptability, and Safety of a 4:3 Intermittent Fasting Weight Loss Program Among Stage I-III Breast Cancer Survivors With Overweight or Obesity: Protocol for a 6-Month Proof-of-Concept Feasibility Trial

Background: Mounting evidence underscores the adverse effects of excess body weight during cancer survivorship, yet many breast cancer survivors struggle to maintain a healthy weight (approximately 70% have overweight or obesity [OW/OB]). Daily caloric restriction with increased physical activity is the standard behavioral weight loss approach; however, many fail to achieve clinically meaningful (>5%) weight loss, emphasizing the need for innovative interventions. A recent investigation found that a behavioral weight loss program focusing on 4:3 intermittent fasting (4:3 IMF) produced 60% greater weight loss among healthy adults with OW/OB with no history of cancer than a program focused on daily caloric restriction. Given these promising results and the need for innovative weight loss strategies among breast cancer survivors, studies testing 4:3 IMF among breast cancer survivors are warranted. Objective: This investigation aimed to evaluate the feasibility, acceptability, and safety of a 4:3 IMF behavioral weight loss program tailored to breast cancer survivors, and to examine exploratory clinical outcomes (eg, body weight, diet adherence, and physical activity) in relation to prespecified thresholds that will inform whether adjustments to the program are needed prior to progression to a larger trial. Methods: In this proof-of-concept feasibility study, individuals with stage I-III breast cancer who have OW/OB and are post-primary therapy will enroll in a 6-month behavioral weight-loss intervention using a 4:3 IMF dietary strategy. Participants will complete a modified fast of approximately 500 kcal per day on 3 non-consecutive days per week, with ad libitum intake the other 4 days per week. Participants will receive virtual, group-based education from a registered dietitian nutritionist that includes a focus on cancer-specific nutrition guidelines. They will also receive in-person, individualized exercise support from an established exercise oncology program to target cancer-specific exercise guidelines. Intervention feasibility will be assessed via participant recruitment, retention, and education class attendance. Acceptability of Intervention Measure, Intervention Appropriateness Measure, Net Promoter Scores, and focus group interviews will be used to assess program acceptability. Proof-of-concept will be evaluated based on whether prespecified thresholds for changes in exploratory clinical outcomes are met. This information will be used to inform progression to a larger trial. Results: This study was funded in January 2022. Data collection began in May 2024 and is ongoing as of April 2026. Recruitment was completed in September 2025 with 31 participants. Study volunteers are currently participating in the 6-month intervention, with data collection anticipated to be completed by Summer 2026, data analysis to begin in Summer/Fall 2026, and initial study results expected by early 2027. Conclusions: This study aimed to examine feasibility, acceptability, and safety of a 4:3 IMF intervention among breast cancer survivors. Data from this study will be used to refine the 4:3 IMF intervention for delivery in a future randomized efficacy trial.