Diet Modification in pAtients With Luminal Early Breast Cancer Candidate for Primary Surgery

Study Overview
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Brief Summary
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to analyze the feasibility for patients with early luminal breast cancer to be compliant with a diet modification - ketogenic or proteins restricted diet - during 9 +/- 1 days, before breast cancer surgery. It's a Pilot study, monocentric, randomized

Detailed Description
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Many patients are modifying their diet after the diagnosis of cancer. There is a supposedly benefit, among the general public, of starving cancer cells with several diet deprivations. Due to the lack of coherent scientific data, no evidence base recommendations can be made regarding the optimal diet during cancer and its effect on cancer growth. The objective of this trial is to analyze the feasibility for patients with early luminal breast cancer to be compliant with a diet modification - ketogenic or proteins restricted diet - during 9 +/- 1 days, before breast cancer surgery. The primary objective of the trial is to evaluate the compliance to the proposed diet. The study will be conducted in patients with luminal early breast cancer, candidate to primary surgery, in order to study an homogeneous population of patients, with good performance status and without nutritional deprivation. Metabolic changes on the main metabolic pathways and the potential antitumor effects related to these metabolic changes following the diet will be analyzed as secondary objectives of the study. We hope to find biological hypotheses to further test in a next larger prospective trial. The impact of the patient's beliefs, anxiety and/or depression on the compliance will be analyzed as well.

Official Title
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Trial Studying the Feasibility of a Diet Modification in pAtients With Luminal Early Breast Cancer Candidate for Primary Surgery

Conditions
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Breast Cancer, Surgery

Intervention / Treatment
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* Dietary Supplement: iso-caloric ketogenic diet
* Dietary Supplement: protein restricted diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women 18 to 80 years old Invasive breast carcinoma, non-metastatic, stage I to III, pathologically proven, ER and/or PR positive, HER2 negative (luminal) No treatment yet for the current breast cancer Candidate for primary surgery Body mass index (BMI) between 18.5 and 30 for women up to 70 years old and between 21 and 30 for women between 70 and 80 years old. For patient ≥ 70 years, score of the Oncodage G8 questionnaire > 14 (if score ≤ 14, consultation with an oncogeriatrician required to validate the possibility of following a diet No addiction (alcohol, tobacco, drug, electronic cigarette) that modifies the metabolism (alcohol : ≤ 2 glasses/d or ≤10 glasses/week ; tobacco : only occasional or stopped for ≥ 6 months) Performance status 0-1 Fasting blood test : Blood cell counts : Neutrophils > 1000/µL, Platelets > 100 000/µL, Hb > 11g/dL Hepatic biology: GOT, GPT, GGT, Phosphatases alcalines < 2x normal value Renal function : clearance > 60 mL /min Lipid profile : Total cholesterol < 1.5 x normal value, HDL>0.35g/L, LDL < 2.2 g/L (<5.7 mml/L), Triglycerides < 1.5 x normal value Fasting blood glucose < 1.26 g/l Measurement of electrolytes: Potassium, Sodium, Calcium, Magnesium (according to normal laboratory values) ECG with a QTc interval ≤ 450 msec Patient able to understand, participate and give a written consent for participation to the study Exclusion Criteria: Metabolic disease or other disease impairing the metabolism analysis High level athlete Unintentional weight loss ≥ 5% during the last month, or 10% during the last 6 months or compared to usual weight Unjustified dietary supplement (not justified by a measured deficiency) during the last month Restricted of unbalanced diet (vegan diet, restricted hypocaloric, hyper or hypo protein…) during the last month Practice of fasting during the last 3 months Corticoids that can't be stopped or not stopped for 2 weeks Mellitus diabetes (with or without insulin) Hypercholesterolemia requiring a treatment Invasive lobular carcinoma Pregnant or breast-feeding women Participation to another study with an investigational treatment during the last 30 days Individuals under the protection of a conservator Unaffiliated patient to Social Protection System.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control arm<br>In the control arm, patients will continue their usual diet without further recommendation. | |
| Experimental: specific diet arm Ketogenic arm<br>In the specific diet arms, the study diet will be calculated with a dietician, for the ketogenic diet, an iso-caloric ketogenic will be proposed and explained to the patient Each diet will be respected by the patient during 9 days +/- 1 day. | Dietary Supplement: iso-caloric ketogenic diet<br>* Each patient will be offered a daily diet plan that includes the different groups of low glycemic index foods to bring to each meal and snack, with the notion of quantity. Carbohydrate-free foods can be consumed ad libitum. Dietary advice will be given to increase the consumption of lipid foods (vegetable oils, butter, cheeses, fatty fish, etc.) so that 65% of the total energy intake is provided by lipids. In addition, a list of unauthorized sugars and sweeteners substitutes will be proposed as well as a low glycemic index food composition table centered on carbohydrates for better control of food choice<br>|
| Experimental: specofoc diet arm protein restricted diet<br>In the specific diet arms, the study diet will be calculated with a dietician, for the protein restricted diet, a 20% protein restriction as compared to the usual diet will be calculated and the diet will be explained to the patient. Each diet will be respected by the patient during 9 days +/- 1 day. | Dietary Supplement: protein restricted diet<br>* A diet reducing by 20% the amount of protein compared to the usual intake of the patient will be proposed. This new ration will be carried out by calculating the proportion of total energy intake provided by the amount of protein reduced by 20% compared to the usual intake, and by modifying lipid and carbohydrate intakes to obtain an isocaloric ration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| study of the compliance of patients to the two proposed diets. The proportion of compliant patients to the proposed diet according to the dietary survey realized during 3 days | A patient is considered compliant to the diet if the caloric intake is equal +/- 25% to the caloric intake of the proposed diet AND For the ketogenic diet : the carbohydrate intake is equal +/- 25% to the carbohydrate intake of the proposed diet; i.e. a carbohydrate intake between 7.5 and 12.5% of the total energy intake For the protein restricted diet, the protein intake is equal +/- 25% to the protein intake proposed for this diet; i.e. a reduction between 15 and 25% compared to the previous protein intake | during 3 days before the primary surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| study of the molecular consequences of diet modifications on cancer cells and their microenvironment | analyse markers of cell proliferation in cancer and immune cells with blood sample and tumor sample. Evaluation of markers involved in carbohydrate mitochondrial and lipid metabolism, and markers of the Pi3K-Akt-mTOR and the IGF-R pathways | At the inclusion visit and the day of surgery | 
| study of the molecular consequences of diet modifications on cancer cells and their microenvironment | determine the activity of the anti-tumoral immune surveillance with blood sample and tumor sample. Correlation between the cancer response and antitumoral immune with diet programm | At the inclusion visit and the day of surgery | 
| evaluation of patient's tolerability to those diet modifications, in terms of weight status | Weight surveillance (in kilograms) | From the inclusion visit until the Day 45 post surgery | 
| evaluation of patient's tolerability to those diet modifications, in terms of adverse events | monitoring of adverse events related to diet (with CTCAE (Common Terminology Criteria for Adverse Events) version 5.0) | From the inclusion visit until the Day 45 post surgery | 
| assessment of the acceptance of study participation and reasons for refusal | Rate of patients who agreed to participate in the study compared to the total number of patients to whom the study was proposed. Collection of reasons for refusing to participate to the study | During 45 days before the surgery | 
| determination of the impact of diet modification on patient's quality of life | Result of the EORTC QLQ-C30 questionnaire (European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire) questionnaire | From the inclusion visit until the Day 45 post surgery | 
| evaluation of the impact of patient's beliefs about diet and cancer on the compliance to the proposed diet. | Result of the questionnaire of Beliefs about diet and cancer OPINELE (Opinions concernant l'alimentation, la santé et le cancer) | From the inclusion visit until the Day 45 post surgery | 
| evaluation of the impact of the patient's anxiety and depression level on the compliance to the proposed diet | Scores obtained on the HADS scale (Hospital Anxiety and Depression Scale) (if score or = 9, result is no significant, if sore is between 10 and 12, result is limit, if result is > or = 13, result is significant | From the inclusion visit until the Day 45 post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dietary survey,