BCDIS: Breast Cancer Diet Intervention Study

Sponsor

Helse Stavanger HF (Other)

Overall Status

Completed

CT.gov ID

NCT03886389

Collaborator

(none)

Enrollment

Arms

96.8

Actual Duration (Months)

Study Details

Study Description

Brief Summary

The investigators have already proven that Mitotic Activity Index (MAI)is the most robust measure of proliferation in breast cancer tissue.

The purpose was to study whether 18 and 2-4 hours pre-operative per-oral carbohydrate loading (often given in gastrointestinal surgery i.e. enhanced recovery after surgery=ERAS) influences proliferation in the tumor, serum insulin characteristics, metabolic profile and survival.

Condition or Disease	Intervention/Treatment	Phase
Early-stage Breast Cancer Carbohydrate Engorgement Proliferation Insulin Resistance Estrogen Receptor-positive Breast Cancer	Dietary Supplement: PreOP	N/A

Detailed Description

It has been postulated that a "Western-style" diet, rich in carbohydrates (especially high glycemic carbohydrates) may have an effect on the incidence of breast cancer, and perhaps also prognosis. This may be mediated through the insulin-related pathways in breast cells which may show insulin-dependent proliferation, which may alter outcome.

Aims:

To study:

The inter-patient variation in insulin and insulin-related characteristics in the blood taken just before the operation from breast cancer patients, on a usual pre-operative fasting schedule;
The influence of the variation in insulin and insulin-related characteristics on proliferation and other cell biological features in the breast cancers of these patients;
Whether 4 and 18-hours pre-operative hyperglycaemic glucose loading (to reduce postoperative insulin resistance) influences proliferation (Mitotic Activity Index (MAI) and other cell biological features in breast cancer*
The influence of the short-term effect of a pre-operative low-glycaemic carbohydrate isocaloric diet on proliferation and other cell biological features of the primary breast cancer cells (Low-glycemic isocaloric diet intervention study);
Epidemiological risk factors: The correlation between epidemiological risk factors, insulin and insulin-related characteristics, proliferation, cell biological features and other biomarkers in breast cancer patients.
Estrogen Receptor positive tumors will be analyses separately.
Relapse free survival
Breast Cancer Specific Survival.

The Short-term effect of carbohydrates will be assessed in a randomized intervention study, where 30 patients receive oral carbohydrates 18 and 4 hours before surgery and 30 patients receive fasting procedure/water.

Primary Outcome

Proliferation in the tumor as measured by MAI.

Secondary Outcomes:

Serum insulin characteristics (S-insulin, S- insulin c-peptide, S-IGF and S-IGFBP3) will be measured at various peri-surgical timepoints
Changes in metabolic profile* in the tumor and in serum samples
Patient Reported Outcome Measures (PROM) on well being
Relapse free survival
Breast Cancer Specific Survival

Metabolic profile assessed by High Resolution Magnetic Resonance Spectroscopy (HR-MRS) in the tumor and in serum samples.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: TreatmentAllocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

The Effects of Insulin and Insulin-related Characteristics, and Short-Term Low-glycemic and High-glycemic Carbohydrate Intervention on Breast Cancer Biomarkers and Survival

Actual Study Start Date :

Jun 12, 2009

Actual Primary Completion Date :

Jul 7, 2017

Actual Study Completion Date :

Jul 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carbohydrate/intervention group Breast cancer patients receive 2 x preoperative carbohydrate loading [PreOP(TM)] before surgery; the 1st dose 18 hours before and 2nd dose 2-4 hours before surgery.	Dietary Supplement: PreOP Mixture of Carbohydrates; standard amount designed for enhanced recovery after surgery (ERAS) i.e. preoperative carbohydrate loading before long standing surgery to enhance recovery.
No Intervention: Control group Breast cancer patients receive standard prep fasting procedure with nil food per os 8-10 hours before surgery, drinking tap water until 2 hours before surgery.

Arm

Intervention/Treatment

Experimental: Carbohydrate/intervention group

Breast cancer patients receive 2 x preoperative carbohydrate loading [PreOP(TM)] before surgery; the 1st dose 18 hours before and 2nd dose 2-4 hours before surgery.

Dietary Supplement: PreOP

Mixture of Carbohydrates; standard amount designed for enhanced recovery after surgery (ERAS) i.e. preoperative carbohydrate loading before long standing surgery to enhance recovery.

No Intervention: Control group

Breast cancer patients receive standard prep fasting procedure with nil food per os 8-10 hours before surgery, drinking tap water until 2 hours before surgery.

Outcome Measures

Primary Outcome Measures

Mitotic Activity Index (MAI) [Trough completion of surgery of all included patients, an average of 1,5 years]
Proliferation in invasive front in tumor

Secondary Outcome Measures

S-Insulin [Analysed in serum samples at 5 time points; At inclusion (day 0), admission (day 10), preoperatively (day 11), postoperatively (day12) and at post operative visit (day 30)]
Secretion of insulin into serum; unit, mIE/L (milli international units pr liter)
Well being after surgery [Day 1,2,3,4,5,6 and 7 after surgery]
Patient Reported Outcome Measures (Questionaire)
High Resolution Magnetic Resonance Spectroscopy (HR-MRS) profiling of specific metabolites [Immediately after surgery: tumor is fresh frozen. High Resolution Magnetic Resonance Spectroscopy (HR-MRS) will be done in the fresh frozen tumor and deep frozen serum samples (=as for insulin characteristics)]
Metabolic profiling in the primary tumor and in the serum samples; measure content of lactate, glycine, choline, fatty acids and lipoproteins
Relapse Free Survival [Until 8 years (97 months of follow up)]
Time from surgery to a relapse (Loco-regional, contralateral and systemic) is experienced
Breast Cancer Specific Survival [8 years follow-up (97 months of follow up)]
Time from surgery to dead of disease or all other causes of death.
S-insulin c-peptide, [Analysed in serum samples at 5 time points; At inclusion (day 0), admission (day 10), preoperatively (day 11), postoperatively (day12) and at post operative visit (day 30)]
Measure of total insulin secreted; unit, nM (nano molar)
S-IGF1 [Analysed in serum samples at 5 time points; At inclusion (day 0), admission (day 10), preoperatively (day 11), postoperatively (day12) and at post operative visit (day 30)]
Measure of Insulin growth factor type 1; unit, nM (nano molar)
S-IGFBP3 [Analysed in serum samples at 5 time points; At inclusion (day 0), admission (day 10), preoperatively (day 11), postoperatively (day12) and at post operative visit (day 30)]
Measure of Insulin growth factor binding protein 3; unit mg/L (milligram per liter)
PR [Trough completion of surgery of all included patients, an average of 1,5 years]
Expression of Progesteron Receptor in the primary tumor

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 100 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

All consecutive operable patients in 2009-2010, with a clinical and/or radiologic and/or cytologic diagnosis of primary breast cancer, unless the exclusion criteria apply.

Exclusion Criteria:

Non-operable patients (i.e" patients with T3-4 (>5 cm) disease or distant metastases at the time of operation).
All patients who refuse to participate.
All patients with DCIS, micro-invasive cancer < 2mm diameter or tumors with histologic poor-quality material.
Co-morbidity (Insulin dependent Diabetes Mellitus, Cushing syndrome, previous or concurrent cancers except CIN and non-melanomatous skin cancer.
Mental inability to participate.
Persons allergic to one of the compounds in any of the two diets.