The Effects of Insulin and Insulin-related Characteristics, and Short-Term Carbohydrate Intervention on Breast Cancer Proliferation

Hypothesis
In breast cancer patients, a high peroral pre-operative glucose load will increase proliferation in endocrine responsive tumors.

Detailed aim
Investigate the effects of a high preoperative carbohydrate loading on  endocrine/ metabolic profile in breast cancer tissue and serum samples, in relation to cancer cell proliferation, recovery and   prognosis.

Design
The study is as an explorative randomized clinical intervention study. It comprises 30 patients with preoperative carbohydrate treatment, and 30 fasting controls.   The study investigates the effects of an intervention consisting of an oral carbohydrate load given 4 and 18 hours ahead of surgery, compared to fasting patients. We will evaluate the immediate postoperative metabolic profiles of patients randomized to receive preoperative carbohydrate loading or normal fasting routines.

Glucose metabolism enhances tumor growth. Locosale J. W. et al, Molecular Symstems Biology (2012) 8, 597.

Methodology
The proliferation in the primary tumor is evaluated by the proliferation index measured by Ki67, Phosphohistone H3 (PPH3), Mitotic Activity Index (MAI) and KAM-score (Ki-67 adjusted mitotic score). The metabolic profiles will be compared to surrogate endpoint biomarkers, which are strongly prognostic, such as the tumor size (pT), grade and proliferation. Serum samples taken before operation and 24 hours post surgery and primary tumor tissue, will be analyzed by MRS in Trondheim. The metabolites, lipoprotein sub fractions, and metabolite profiles will be evaluated together with previously obtained parameters of insulin, insulin-related parameters, pathological and molecular biology features of the tumor, and patient clinical factors.

PI: Håvard Søiland, Stavanger University Hospital.