Fasting for Breast Cancer

(GAMMER Trial)

Overseen By Jennifer Sheng, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Food-required medications

Disqualifiers: Diabetes, Eating disorder, Uncontrolled conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to test the feasibility of 24-48 hours of water-only fasting to improve delivery of 4 cycles of chemotherapy in those receiving breast cancer treatment either before or after surgery.

Will I have to stop taking my current medications?

If you are taking medications that must be taken with food, such as aspirin, lithium, or prednisone, you may need to stop them to participate in this trial. The protocol does not specify other medication restrictions.

What data supports the effectiveness of the treatment Fasting, Intermittent Fasting, Continuous Calorie Energy Reduction (CER), Weight Loss Interventions for breast cancer?

Research suggests that intermittent fasting and continuous calorie reduction may help prevent breast cancer by reducing factors like insulin and IGF-1, which are linked to cancer growth. Additionally, fasting during chemotherapy may reduce side effects and improve treatment effectiveness. ^{1 2 3 4 5}

Is fasting safe for humans?

Some studies suggest that intermittent fasting and energy restriction can be safe for humans, as they have been shown to lead to weight loss and improve insulin sensitivity without major side effects in short-term trials. However, more long-term studies are needed to fully understand their safety. ^{3 4 5 6 7}

How does fasting differ from other treatments for breast cancer?

Fasting, particularly intermittent fasting, is unique because it may enhance the effectiveness of existing breast cancer treatments like chemotherapy and endocrine therapy by making cancer cells more vulnerable and reducing side effects. Unlike traditional treatments, fasting focuses on dietary patterns to potentially improve treatment outcomes and quality of life. ^{2 3 4 5 6}

Research Team

Jennifer Sheng, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

This trial is for individuals undergoing chemotherapy for breast cancer, either before or after surgery. Participants will try water-only fasting for 24-48 hours to see if it helps with the treatment.

Inclusion Criteria

Willingness to change diet, and provide fecal sample 3 times during study

Provider physical exam within 4 weeks of consent

BMI ≥ 19.5 kg/m2 (as per most recent visit documented in medical record)

Exclusion Criteria

I have diabetes.

I do not have any severe medical conditions like kidney failure, uncontrolled high blood pressure, or liver cirrhosis.

BMI <19.5 kg/m2

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Participants undergo a dose finding for fasting, requiring at least one successful 24-hour fast with a maximum of three trials allowed.

1-3 weeks

Up to 3 visits (in-person)

Chemotherapy with Fasting

Participants receive chemotherapy with a fasting regimen, consisting of 4 cycles of chemotherapy with fasting interventions.

8-12 weeks

4 visits (in-person) for chemotherapy cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cytokines, metabolites, and gut microbiome.

6-8 months

Treatment Details

Interventions

• Fasting

Trial Overview The study is testing whether short-term fasting can make chemotherapy more effective in treating breast cancer. Patients will fast for one to two days during their chemo cycles.

Participant Groups

Group I: Fasting prior to chemotherapy Experimental Treatment 1 Intervention

Prior to chemotherapy administration, a trial of a 24-hour water-only fast will be conducted; at least 1 successful 24-hour fast is required to proceed with the fasting intervention during chemotherapy. A total of 3 trials is allowed (for a maximum of 48 hours fasting).

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

The Commonwealth Fund

Collaborator

Trials

13

Recruited

228,000+

Maryland Cigarette Restitution Fund

Collaborator

Trials

10

Recruited

900+

Findings from Research

Periodic fasting enhances the effectiveness of endocrine treatments for hormone receptor-positive breast cancer by increasing their anti-cancer activity.

Fasting may help delay the development of resistance to these treatments by lowering levels of blood leptin, insulin, and insulin-like growth factor 1 (IGF1), suggesting a potential new strategy for improving breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing endocrine therapy activity via fasting cycles: biological rationale and clinical feasibility. Caffa, I., Nencioni, A.[2021]

Intermittent fasting (IF) during chemotherapy for breast cancer patients was found to be feasible and safe, potentially alleviating chemotherapy-induced adverse effects like fatigue and nausea, although the quality of the data was low.

While IF showed some promise in reducing chemotherapy-induced DNA damage and improving glycemic regulation, the review did not find significant benefits on quality of life or tumor recurrence, indicating that more rigorous studies are needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Fasting in Breast Cancer: A Systematic Review and Critical Update of Available Studies. Anemoulis, M., Vlastos, A., Kachtsidis, V., et al.[2023]

Habitual continuous energy restriction (CER) has been shown to effectively prevent breast tumor formation in both animal studies and observational studies in women, while intermittent energy restriction (IER) and intermittent fasting (IF) may offer easier and potentially more effective alternatives for weight control and cancer prevention.

Animal studies suggest that IER and IF can reduce mammary tumor formation and may have different mechanisms of action compared to CER, including greater reductions in fat stores and improved insulin sensitivity, but more research is needed to directly compare these methods in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy restriction and the prevention of breast cancer. Harvie, M., Howell, A.[2013]

Preliminary findings indicate that combining intermittent fasting or a fasting-mimicking diet with endocrine therapy may enhance the effectiveness of treatment for hormone receptor-positive breast cancer.

This combination approach could also help in reducing side effects associated with the endocrine therapy, suggesting a potential strategy for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting May Complement Endocrine Therapy. [2021]

Intermittent fasting (IF) during chemotherapy for breast cancer patients significantly reduced gastrointestinal toxicity compared to a non-fasting group, suggesting a protective effect of fasting against chemotherapy side effects.

The study, involving 48 HER2-negative breast cancer patients, also indicated that IF improved metabolic profiles, as evidenced by lower insulin levels in the IF group, which may enhance the overall efficacy of chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent fasting during adjuvant chemotherapy may promote differential stress resistance in breast cancer patients. Omar, EM., Omran, GA., Mustafa, MF., et al.[2022]

Intermittent energy restriction (IER) led to a significant weight loss of 4.8% and reduced insulin resistance by nearly 30% during restricted days in 23 overweight premenopausal women at high risk for breast cancer, suggesting potential metabolic benefits.

The study found variable transcriptional responses in breast tissue to IER, with some women showing beneficial gene expression changes related to breast epithelial cell differentiation, while others did not exhibit any significant changes, indicating that individual responses to IER may differ and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent energy restriction induces changes in breast gene expression and systemic metabolism. Harvie, MN., Sims, AH., Pegington, M., et al.[2022]

Intermittent energy restriction (IER) has been shown in animal studies to be more effective than continuous energy restriction (CER) in reducing tumor rates, suggesting potential anticancer benefits.

Limited human studies indicate that IER may improve insulin sensitivity more than CER in overweight and obese individuals, but more long-term research is needed to confirm these findings and assess safety and efficacy in both overweight and normal-weight populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence. Harvie, MN., Howell, T.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Enhancing endocrine therapy activity via fasting cycles: biological rationale and clinical feasibility. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Intermittent Fasting in Breast Cancer: A Systematic Review and Critical Update of Available Studies. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Energy restriction and the prevention of breast cancer. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Fasting May Complement Endocrine Therapy. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Intermittent fasting during adjuvant chemotherapy may promote differential stress resistance in breast cancer patients. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Intermittent energy restriction induces changes in breast gene expression and systemic metabolism. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence. [2023]