4:3 Intermittent Fasting Intervention in Adults With Breast Cancer and Overweight or Obesity

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Age 18-65 years

• Body Mass Index 25-45 kg/m2

• Diagnosis of stage 1-3 breast cancer within the past 10 years with completion ofstandard of care definitive surgery, adjuvant chemotherapy, radiation, immunotherapyand/or targeted therapy as appropriate prior to the intervention start date.Completion of definitive surgery must be ≥ 3 months prior to the intervention startdate, other therapies must be completed ≥ 1 month prior to the intervention startdate (however exceptions to this 1-month timeframe for completion of other therapiescan be made on a case-by-case basis by the PI if patients are tolerating therapywithout adverse effects and will have completed treatment prior to the interventionstart date). Current/ongoing use of anti-endocrine directed therapy for breastcancer (including ovarian suppression, tamoxifen, aromatase inhibitors, selectiveestrogen degraders) is acceptable as long as participants have been on therapy for ≥3 months prior to the intervention start date.

• Live or work within 30 miles of the AHWC (exceptions may be made at the discretionof the Study PI on a case-by-case basis for highly motivated subjects).

• Capable and willing to give informed consent and understand exclusion criteria,willing to attend weekly small group sessions held by a registered dietitian, andattend one in person BfitBwell exercise sessions per week.

• Have a primary care provider (PCP) (or are willing to establish care with a PCPprior to study enrollment) to address medical issues which may arise duringscreening or study procedures/interventions.

• Obtain a signed medical clearance from their medical provider for participation inthe 4:3 IMF dietary intervention and BfitBwell clinical exercise oncology program.

• Own or willing to purchase a smart phone or computer to join Zoom meetings, completequestionnaires, and access/download the True Coach virtual exercise coachingsessions.

All interested individuals will complete a brief online eligibility screener through REDCap to confirm initial eligibility.

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status 2 or higher.

• Actively undergoing chemotherapy, radiation, immunotherapy and/or targeted therapy (other than anti-endocrine therapy) or are within 1 month of completion ofchemotherapy, radiation, immunotherapy and/or targeted therapy (other thananti-endocrine therapy) as of the target intervention start date. Exceptions to this 1-month timeframe can be made on a case-by-case basis at the discretion of the PI ifpatients are tolerating therapy without adverse effects and will have completedtreatment prior to the intervention start date.

• Plans to relocate within the next 12 months.

• Plans for extended travel (>2 weeks) within the next 12 months.

• Major surgery within the past 3 months (including mastectomy or breastreconstruction but not including lumpectomy or other minor surgeries) or plannedmajor surgery (including mastectomy or breast reconstruction) during the timeframeof the 6 month study intervention and follow-up phases.

• For Females:

• Currently pregnant or lactating.

• Pregnant within the past 6 months.

• Planning to become pregnant in the next 12 months; sexually active women ofchildbearing potential may be enrolled if they have had a tubal ligation or usea reliable means of contraception.

• Recent (past 6 months) acute coronary event, unstable angina, coronaryrevascularization, stroke, pulmonary embolism, or hospitalization for heart failureor cardiac arrythmia.

• Symptoms suggestive of cardiovascular disease or unstable angina (e.g., chest pain,shortness of breath at rest or with mild exertion, lightheadedness, syncope).

• Uncontrolled hypertension, defined as diastolic blood pressure >100 mmHG, systolicblood pressure >160 mmHG, or resting heart rate >100 bpm as measured in duplicate onthe screening visit after 5 minutes of rest in a seated position.

• Diabetes (history of type 1 or type 2 diabetes or fasting glucose ≥126 mg/dL orHemoglobin A1C ≥6.5% as measured on screening labs) unless on metformin or ondipeptidyl peptidase IV (DPP-IV) inhibitor monotherapy and well-controlled withHemoglobin A1C <8%.

• Undiagnosed hypo- or hyper-thyroidism (TSH outside of the normal range as measuredon screening labs) or history of uncontrolled thyroid disorder. History of thyroiddisease or current thyroid disease treated with a stable medication regimen isacceptable.

• Stage 4 or 5 chronic kidney disease as assessed by estimated glomerular filtrationrate <30 as measured on screening labs.

• Triglycerides >500 mg/dL or LDL cholesterol >200 mg/dL as measured on screeninglabs.

• Serious arrhythmias, including multifocal PVC's, frequent PVC's (defined as 10 ormore per min), ventricular tachycardia (defined as runs of 3 or more successivePVC's), or sustained atrial tachyarrhythmia; 2nd or 3rd degree A-V block, known QTcinterval > 480 msec or other significant conduction defects.

• Clinically significant abnormalities in hematocrit/hemoglobin, white blood cellcount, platelets, serum sodium, potassium, or bicarbonate as measured on screeninglabs or presence or history of other metabolic or chronic health problems whichwould impact ability to safely participate in a weight loss intervention involvingan intermittent energy restricted diet and exercise including significant cardiacvalvular disease or heart failure, significant gastrointestinal, pulmonary, renal,musculoskeletal, neurologic, hematologic, orthopedic, or psychiatric disease.

• Sustained use of prescription or over-the-counter medications known to significantlyimpact appetite, weight, or energy metabolism (e.g., anti-obesity pharmacotherapy,appetite suppressants, lithium, stimulants, anti-psychotics, tricyclicantidepressants) with the exception of anti-endocrine directed treatment for breastcancer and standard of care anti-emetic or anti-diarrheal agents.

• Sustained use of systemic glucocorticoids (current or in the past 6 months) unlessphysiologic replacement therapy for adrenal insufficiency.

• Previous obesity treatment with metabolic bariatric surgery or weight loss device,except: (1) liposuction and/or abdominoplasty if performed > 1 year beforescreening, (2) lap banding if the band has been removed > 1 year before screening, (3) intragastric balloon if the balloon has been removed > 1 year before screening (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year beforescreening or 5) AspireAssist or other endoscopically placed weight loss device ifthe device has been removed > 1 year before screening.

• Nicotine use (current or past 6 months)

• Current alcohol or substance abuse.

• History of clinically diagnosed eating disorders including anorexia nervosa,bulimia, binge eating disorder. Score >20 on the Eating Attitudes Test (EATS-26) orpattern of response on the Questionnaire of Eating and Weight Patterns (QEWP-5)suggestive of possible binge eating disorder or bulimia will require furtherassessment by the Study MD to determine if it is appropriate for the subject toparticipate in the study.

• Current severe depression or history of severe depression within the previous year,based on DSM-IV-TR criteria for Major Depressive Episode or history of othersignificant psychiatric illness (e.g., psychosis, schizophrenia, mania, bipolardisorder) which in the opinion of the Study PI would interfere with ability toparticipate in the diet and exercise interventions and provide feedback on theinterventions via questionnaires and focus groups.

• Currently participating in or planning to participate in any formal weight loss orphysical activity programs or clinical trials over the next 12 months.

• Previous participation (within the past 3 years) in the Anschutz Health and WellnessCenter (AHWC) BfitBwell Oncology Exercise Program (exceptions may be made at thediscretion of the study PI).

• Previous participation (within the past 3 years) in a weight loss, exercise, ornutrition research study (exceptions may be made at the discretion of the study PI).

Children (individuals under the age of 18 years per NIH guidelines) will not be recruited for the current studies because breast cancer is rare in children and because the lifestyle weight management curriculum used in the study was not designed for children or adolescents.

We have elected to exclude adults over the age of 65 years as weight loss may not be advisable in older patients undergoing treatment for breast cancer or in routine follow-up for breast cancer due to issues with loss of lean mass and decreases in functional capacity that can occur with weight loss in older individuals. A separate study on the impact of a lifestyle weight loss intervention in older patients with breast cancer is warranted.