What is the mechanism of action of this treatment?

The ketogenic diet, which induces ketosis by significantly reducing carbohydrate intake, may help in managing breast cancer by altering metabolic pathways that cancer cells rely on for growth. Letrozole, an aromatase inhibitor, works by blocking the enzyme aromatase, which converts androgens to estrogens, thereby reducing estrogen levels in the body. This is particularly important for estrogen receptor-positive (ER+) breast cancer patients, as their cancer cells depend on estrogen to grow. Combining these treatments could potentially enhance the anti-cancer effects by simultaneously targeting metabolic and hormonal pathways, offering a multifaceted approach to treatment.

What side effects are associated with this type of intervention?

The combination of a very low carbohydrate ketogenic diet and letrozole, an aromatase inhibitor, is being studied for its effects on breast cancer. Common side effects of a ketogenic diet can include gastrointestinal issues, fatigue, headache, and dizziness due to the body's adaptation to ketosis. Letrozole, on the other hand, is associated with side effects such as hot flashes, joint pain, fatigue, increased sweating, and potential bone density loss. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

Letrozole, an aromatase inhibitor, is FDA-approved for treating hormone receptor-positive breast cancer in postmenopausal women. Other FDA-approved aromatase inhibitors include anastrozole and exemestane. These drugs reduce estrogen levels to slow the growth of estrogen receptor-positive breast cancer. Additionally, tamoxifen, a selective estrogen receptor modulator, is approved for both premenopausal and postmenopausal women with hormone receptor-positive breast cancer.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) CDK4/6 inhibitors (e.g., Palbociclib, Ribociclib) which are used in combination with hormonal therapies to inhibit cancer cell proliferation. 2) PARP inhibitors (e.g., Olaparib) for patients with BRCA mutations, which prevent cancer cells from repairing DNA damage. 3) Immunotherapy agents (e.g., Pembrolizumab) that enhance the body's immune response against cancer cells. 4) Newer hormonal therapies such as selective estrogen receptor degraders (SERDs) like Elacestrant, which degrade estrogen receptors and inhibit cancer growth.

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Hormone Therapy

Ketogenic Diet + Letrozole for Breast Cancer

Phase < 1

Waitlist Available

Led By Brent Rexer, MD, PhD

Research Sponsored by Vanderbilt-Ingram Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

The primary tumor size must be at least 2 mm in size.

Patients must have clinical stage I, II, or III invasive mammary carcinoma planning to undergo surgical treatment with either segmental resection or total mastectomy.

Must not have

Severe uncontrolled malabsorption condition or disease (e.g. grade II/III diarrhea, severe malnutrition, short gut syndrome).

Patients with locally advanced disease who are candidates for other preoperative (chemo)therapy at the time of initial evaluation. This includes patients with inflammatory breast cancer.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up after 2 weeks of a ketogenic diet

Awards & highlights

Approved for 10 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests if a low-carb diet combined with letrozole can help prepare early-stage ER+ breast cancer patients for surgery by slowing down cancer cell growth. Letrozole reduces estrogen levels in postmenopausal women, thereby decreasing its ability to stimulate breast cancer cells.

Who is the study for?

This trial is for post-menopausal women with a BMI of 30 or higher, diagnosed with early stage operable ER+ and HER2- breast cancer. They must have adequate organ function, no severe uncontrolled conditions affecting nutrient absorption, not be on insulin for diabetes, and cannot be undergoing other cancer treatments or participating in another neoadjuvant clinical trial.

What is being tested?

The study tests the combination of a very low carbohydrate ketogenic diet for two weeks with letrozole medication to see how well patients tolerate it and its effect on PI3K signaling pathways in estrogen receptor-positive breast cancer.

What are the potential side effects?

Potential side effects may include those associated with a ketogenic diet such as fatigue, headache, dizziness, constipation, nutrient deficiencies and those related to Letrozole like hot flashes, joint pain, weakness and bone thinning over long-term use.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My primary tumor is at least 2 mm big.

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I have stage I, II, or III breast cancer and plan to have surgery.

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My breast cancer has been confirmed by tissue analysis.

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My kidney, liver, and blood tests are within the required ranges.

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My tumor is estrogen receptor positive.

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My tumor does not have the HER2 protein.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have severe digestive issues like ongoing bad diarrhea or extreme malnutrition.

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I have advanced local cancer and can receive chemo before surgery.

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I use insulin to manage my diabetes.

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I am not on any cancer treatment except for hormone therapy.

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My cancer has spread to distant parts of my body (stage IV).

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ after 2 weeks of a ketogenic diet

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~after 2 weeks of a ketogenic diet

This trial's timeline: 3 weeks for screening, Varies for treatment, and after 2 weeks of a ketogenic diet for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Patients who complete the dietary intervention

Secondary study objectives

Measure changes in body composition

Measure changes in insulin resistance

Measure enhanced inhibition of cancer cell proliferation

+1 more

Side effects data

From 2020 Phase 3 trial • 502 Patients • NCT03096847

46%

NEUTROPENIA

43%

NAUSEA

38%

FATIGUE

33%

ALOPECIA

25%

NASOPHARYNGITIS

20%

LEUKOPENIA

20%

DIARRHOEA

20%

ASPARTATE AMINOTRANSFERASE INCREASED

19%

ARTHRALGIA

19%

ALANINE AMINOTRANSFERASE INCREASED

18%

CONSTIPATION

18%

ANAEMIA

17%

HEADACHE

17%

VOMITING

15%

NEUTROPHIL COUNT DECREASED

15%

STOMATITIS

14%

INSOMNIA

13%

PAIN IN EXTREMITY

13%

BACK PAIN

13%

DYSPNOEA

12%

HOT FLUSH

11%

THROMBOCYTOPENIA

11%

RASH

11%

OEDEMA PERIPHERAL

11%

DECREASED APPETITE

10%

URINARY TRACT INFECTION

10%

WHITE BLOOD CELL COUNT DECREASED

10%

COUGH

10%

PRURITUS

ELECTROCARDIOGRAM QT PROLONGED

DYSPEPSIA

VERTIGO

MUSCULOSKELETAL PAIN

DRY SKIN

GAMMA-GLUTAMYLTRANSFERASE INCREASED

LACRIMATION INCREASED

ABDOMINAL PAIN UPPER

WEIGHT DECREASED

ABDOMINAL PAIN

PYREXIA

BLOOD CREATININE INCREASED

BONE PAIN

DRY MOUTH

ERYTHEMA

DRY EYE

DIZZINESS

SLEEP DISORDER

HYPERTENSION

MYALGIA

CYSTITIS

DYSGEUSIA

DEPRESSION

GENERAL PHYSICAL HEALTH DETERIORATION

BRONCHITIS

MUSCULOSKELETAL CHEST PAIN

POLYNEUROPATHY

SEASONAL ALLERGY

PLEURAL EFFUSION

HYPOCALCAEMIA

URETEROLITHIASIS

SKIN ULCER

ARTHROPOD BITE

GASTROINTESTINAL INFECTION

OROPHARYNGEAL PAIN

INFLUENZA

DEVICE RELATED INFECTION

METASTASES TO SPINE

CHEST PAIN

CYSTITIS ESCHERICHIA

SEPSIS

INCISIONAL HERNIA

COLON CANCER

METASTASES TO BONE

PULMONARY EMBOLISM

ATRIAL FIBRILLATION

ANAL HAEMORRHAGE

HELICOBACTER GASTRITIS

TUMOUR LYSIS SYNDROME

TUMOUR PAIN

WEIGHT INCREASED

PANIC ATTACK

FLANK PAIN

SPINAL PAIN

FEBRILE NEUTROPENIA

CARDIAC FAILURE

ILEUS

INTESTINAL STRANGULATION

COMPLICATION OF DEVICE INSERTION

IMPAIRED HEALING

PAIN

HEPATIC CIRRHOSIS

ABSCESS JAW

APPENDICITIS

MASTITIS

PNEUMONIA

HIP FRACTURE

JAW FRACTURE

RADIUS FRACTURE

BLOOD BILIRUBIN INCREASED

HYPERCALCAEMIA

HYPERKALAEMIA

DEVICE LOOSENING

RENAL FAILURE

RENAL IMPAIRMENT

CIRCULATORY COLLAPSE

TOOTHACHE

BLOOD LACTATE DEHYDROGENASE INCREASED

HYPOAESTHESIA

HYPERFIBRINOLYSIS

DRUG-INDUCED LIVER INJURY

ABDOMINAL PAIN LOWER

DEHYDRATION

OSTEITIS

100%

80%

60%

40%

20%

Study treatment Arm

Ribociclib + Letrozole Cohort B2

Ribociclib + Letrozole Cohort A

Ribociclib + Letrozole Cohort B1

Total

Ribociclib + Letrozole Cohort B

Awards & Highlights

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: 2-Week Ketogenic DietExperimental Treatment2 Interventions

2-Week Ketogenic Diet in Combination with Letrozole

Group II: Letrozole ControlActive Control1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

2-Week Ketogenic Diet

2019

Completed Early Phase 1

~40

Letrozole

FDA approved

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The ketogenic diet, which induces ketosis by significantly reducing carbohydrate intake, may help in managing breast cancer by altering metabolic pathways that cancer cells rely on for growth. Letrozole, an aromatase inhibitor, works by blocking the enzyme aromatase, which converts androgens to estrogens, thereby reducing estrogen levels in the body. This is particularly important for estrogen receptor-positive (ER+) breast cancer patients, as their cancer cells depend on estrogen to grow. Combining these treatments could potentially enhance the anti-cancer effects by simultaneously targeting metabolic and hormonal pathways, offering a multifaceted approach to treatment.

Effect of a high dosage of ketoconazole all or not combined with ovariectomy on N-nitroso-N-methylurea-induced mammary cancer in the rat.Aromatase and breast cancer.

Find a Location

Who is running the clinical trial?

Vanderbilt-Ingram Cancer CenterLead Sponsor

218 Previous Clinical Trials

64,325 Total Patients Enrolled

28 Trials studying Breast Cancer

6,594 Patients Enrolled for Breast Cancer

Brent Rexer, MD, PhD3.52 ReviewsPrincipal Investigator - Vanderbilt Medical Center

Vanderbilt-Ingram Cancer Center

1 Previous Clinical Trials

35 Total Patients Enrolled

2Patient Review

At my first appointment with Dr. Rexer, he seemed to understand the material. We discussed estrogen blockers, and he said that if I had trouble after a few months on one, he would switch me to another. However, he then said that if I had trouble right away, he wouldn’t buy it — implying that all women’s bodies work alike, and so if I had trouble it could only mean I was trying to get away with something. My husband and I were stunned. I understand that anti-cancer drugs are harsh, but I need any doctor I use to treat me as an individual with compassion.