This is a neoadjuvant study to determine the feasibility and tolerability of 2 weeks of a very low carbohydrate ketogenic diet in combination with letrozole for patients with early stage operable ER+disease.

Primary Objective:

• To evaluate the feasibility and tolerability of a 2 week ketogenic diet in combination with endocrine therapy prior to surgery for early stage ER+ breast cancer.

Secondary Objectives

• To determine whether endocrine therapy in combination with a dietary intervention to reduce insulin pathway signaling results in enhanced inhibition of cancer cell proliferation (measured byKi67)
• To determine the effectiveness of 2 weeks of a ketogenic diet to reduce measures of insulin/PI3Kpathway activation in breast tumors
• To measure changes in weight and body composition after 2 weeks of a ketogenic diet
• To measure changes in insulin resistance after 2 weeks of a ketogenic diet
• To measure the effectiveness of a ketogenic diet in combination with endocrine therapy to induce and maintain a ketogenic state.

Outline:

Participants will have baseline metabolic parameters measured and will begin a 2-week diet consisting of meal replacement shakes to induce a ketogenic state. Patients will also receive letrozole 2.5 mg daily. At the end of 2 weeks, metabolic parameters will again be measured and patients will proceed with surgical treatment of their breast cancer. A tumor biopsy from the surgical specimen will be obtained to measure cell proliferation compared with the pre-treatment diagnostic biopsy.

Inclusion Criteria:

• All participants must provide written informed consent.

• Patients must have histologically confirmed primary invasive mammary carcinoma

  • The tumor must be estrogen receptor positive
  • The tumor must be HER2 negative (negative IHC or FISH)
  • The primary tumor size must be at least 2 mm in size.

• Patients must be post-menopausal defined by any of the following:

  • Subjects at least 55 years of age.
  • Subjects younger than 55 years of age and amenorrheic for at least 12 months or serum follicle-stimulating hormone (FSH) levels and estradiol levels in the post-menopausal range by local lab criteria
  • Subjects with history of bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months.

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

• Patients must have BMI >= 30.

• A core biopsy from the time of diagnosis must be available.

• Mammogram or ultrasound required prior to screening

• Patients must have adequate organ function based on the following laboratory parameters:

  • Serum creatinine <= 1.5x ULN
  • SGOT, SGPT <= 4x ULN (unless known steatohepatitis)
  • Serum albumin >= 2.0 g/dL
  • Total serum bilirubin <= 1.5x ULN (or <= 3x ULN if known Gilbert's syndrome)

Exclusion Criteria:

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.

• Evidence of distant metastatic disease (stage IV).
• Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
• Serious medical illness that in the judgment of the treating physician would preclude the use of a ketogenic diet.
• Severe uncontrolled malabsorption condition or disease (e.g. grade II/III diarrhea, severe malnutrition, short gut syndrome).
• Diabetes mellitus requiring insulin therapy.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Participation in any other neoadjuvant therapeutic clinical trial.
• Concurrent anti-cancer therapy other than endocrine therapy (e.g. chemotherapy, radiotherapy, immunotherapy, or any other biologic therapy).
• Concurrent treatment with an investigational agent.
• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first day of dietary intervention.