Metabolic subgrouping of breast cancer patients from the Oslo2 study

Can metabolic subgrouping contribute to improved precision medicine?

Breast cancer is a very heterogeneous disease, leading to different prognosis and treatment response among patients with similar clinical diagnosis. Examining the mechanisms leading to heterogeneity among breast cancer patients, may provide a better understanding of how different tumors develop and how the cancer can be cured. Previous studies have shown that breast cancer patients can be divided into prognostic subgroups based on differences in gene expression profiles. In this study, researchers at the MR Cancer group are examining the expression of metabolites in tumor tissue from 228 breast cancer patients that is part of the Oslo-2 study. The metabolic expression is measured by magnetic resonance spectroscopy (MRS), and using this method we can measure the concentration of approximately 30 metabolites in breast cancer tissue. Metabolic profiles are combined with gene- and protein expression data from surrounding tissue from the same tumors.

Three subgroups of patients with different metabolic tissue profiles have been defined; metabolic cluster 1 (Mc1), Mc2 and Mc3 (you can read more about this here and here) (figure 1). Comparison of the clusters showed that Mc1 has a high expression of metabolites taking part in synthesis of phosphatidylcholines, which are important constituents of the cell membrane, thus this subgroup may be characterized by high proliferation. Mc2 has a high level of glucose and possibly a less aggressive cancer, while Mc3 has low glucose and high lactate levels. Combined analysis of metabolite and gene expression data supports these findings. We will further examine the prognostic potential of the metabolic clusters.

Figure 1: Three metabolic subgroups of breast cancer (figure from Haukaas et al, Cancer Metab 2016).

PI: Tone F. Bathen, NTNU.