Carbohydrate Engorgement, Early-stage Breast Cancer, Estrogen Receptor-positive Breast Cancer, Insulin Resistance, Proliferation
Conditions
Keywords
Breast Cancer, Estrogen receptor positive, Proliferation, Insulin resistance, PROMs, NMRI, RFS, BCSS
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.
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: 1. 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; 2. 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; 3. 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\* 4. 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); 5. 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. 6. Estrogen Receptor positive tumors will be analyses separately. 7. Relapse free survival 8. 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 1\. Proliferation in the tumor as measured by MAI. Secondary Outcomes: 1. Serum insulin characteristics (S-insulin, S- insulin c-peptide, S-IGF and S-IGFBP3) will be measured at various peri-surgical timepoints 2. Changes in metabolic profile\* in the tumor and in serum samples 3. Patient Reported Outcome Measures (PROM) on well being 4. Relapse free survival 5. Breast Cancer Specific Survival * Metabolic profile assessed by High Resolution Magnetic Resonance Spectroscopy (HR-MRS) in the tumor and in serum samples.
Interventions
DIETARY_SUPPLEMENTPreOP
Mixture of Carbohydrates; standard amount designed for enhanced recovery after surgery (ERAS) i.e. preoperative carbohydrate loading before long standing surgery to enhance recovery.
Sponsors
Helse Stavanger HF
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) |
| 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 |
| 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) |
Outcome results
None listed