Breast Cancer, Triple Negative Breast Cancer
Conditions
Brief summary
Given preliminary data demonstrating that methionine deprivation enhances cell surface expression of TRAIL receptor-2, the objective of this clinical trial is to confirm that methionine restriction enhances its expression in triple negative breast cancer and to establish the feasibility and acceptability of this dietary intervention in humans. This study will also examine the effect of methionine restriction on cancer stem cells and metabolic health.
Detailed description
Under the supervision of a registered dietitian, subjects will receive an individualized dietary prescription that incorporates a methionine-free amino acid-modified medical food (Hominex-2, Abbott Nutrition) supplemented with low-methionine foods. Hominex-2 contains a mixture of L-amino acids but lacks methionine. Subjects will be instructed in the preparation of Hominex-2 beverages (approximately 4-5 per day or per dietician recommendation) to deliver 100% of daily protein requirements (0.8 g/kg/day) and 40-45% of the caloric requirements. The remaining calories will be met with low-methionine foods, including fruits, vegetables, grains (e.g., specified cereal and bread), margarine and cooking oils. Subjects will be provided with a list of foods that are low in methionine. Calories will not be restricted. Subjects will be encouraged to follow their usual level of physical activity and instructed to maintain a daily diet and exercise diary that will be reviewed weekly by the dietitian.
Interventions
DIETARY_SUPPLEMENThominex-2
Hominex-2 is a methionine-free amino acid modified medical supplement
Sponsors
Avon Foundation
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have histologically confirmed operable triple negative breast cancer * ER (estrogen receptors) and PR (progesterone receptors) expression must be \< 2% * HER2 must negative as shown be either 0 or 1+ by immunohistochemistry (if 2+, in situ hybridization method used to define HER2) OR by a HER2: 17 centromere signal of \<2.0 using a standard in situ hybridization method. * No prior therapy for current breast cancer * Operable breast cancer. Participants who are planned to undergo neo-adjuvant chemotherapy are eligible as long as they consent to an additional breast biopsy following the dietary intervention immediately prior to starting chemotherapy * ECOG (Eastern Cooperative Oncology Group) performance status ≤1 * Ability to understand and the willingness to sign a written informed consent document * Serum creatinine \<ULN (upper limit of normal) * Non-pregnant. Women of childbearing potential must have a negative pregnancy test to participate in this study * Women of childbearing potential must agree to use effective contraceptives (as discussed with their physician) while participating in this study
Exclusion criteria
* Patients who are receiving any other investigational agents * Patients not able to swallow oral medications or with gastrointestinal conditions that may impact absorption of oral medications * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cell surface expression of TRAIL receptor-2 | Up to 3 weeks | To determine if methionine restriction can enhance the cell surface expression of TRAIL receptor-2 in triple negative breast cancers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of methionine restriction on cancer stem cell markers CD44 and CD24 | Up to 3 weeks | To examine the effect of methionine restriction on the expression of the cancer stem cell markers CD44 and CD24 by immunohistochemistry. Five to ten slides from each time point will be evaluated from baseline and after completion of the methionine restricted diet. |
| Change in plasma concentrations | Up to 3 weeks | To evaluate plasma concentrations of methionine and methionine metabolites before and after methionine restriction. Blood will be collected after an overnight fast before dietary methionine restriction, weekly during methionine restriction and at the completion of the diet. Plasma concentration will be determined by high-throughput targeted LC-MS (liquid chromatography--mass spectrometry) assay. |
| Change in subject weight | Up to 3 weeks | To evaluate subject weight before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1). |
| Safety and tolerability of methionine measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Up to 3 weeks | To examine the safety and tolerability of methionine restriction in participants with operable triple-negative breast cancer, measured by the number of participants with treatment-related adverse events as assessed by CTCAE v4.0. |
| Change in subject waist circumference | Up to 3 weeks | To evaluate subject BMI, waist circumference and metabolic indices before and after dietary methionine restriction. Waist circumference will be measured before starting the diet and weekly (every 7 days +/- 1) while on the methionine restricted diet. |
| Change in subject metabolic indices | Up to 3 weeks | To evaluate subject metabolic indices before and after dietary methionine restriction. |
| Change in body composition | Up to 3 weeks | To evaluate body composition before and after dietary methionine restriction |
| Change in subject BMI | Up to 3 weeks | To evaluate subject BMI before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1). |
Countries
United States
Outcome results
None listed