a 2-week ketogenic diet in combination with letrozole to modulate pi3k signaling in er+ breast cancer

Conditions: Estrogen Receptor-positive Breast Cancer

Summary: 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.

Eligibility criteria:
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.