BACKGROUND: MammaPrint was developed as a diagnostic tool to predict risk of 
breast cancer metastasis using the expression of 70 genes. To better understand 
the tumor biology assessed by MammaPrint, we interpreted the biological 
functions of the 70-genes and showed how the genes reflect the six hallmarks of 
cancer as defined by Hanahan and Weinberg.
RESULTS: We used a bottom-up system biology approach to elucidate how the 
cellular processes reflected by the 70-genes work together to regulate tumor 
activities and progression. The biological functions of the genes were analyzed 
using literature research and several bioinformatics tools. Protein-protein 
interaction network analyses indicated that the 70-genes form highly 
interconnected networks and that their expression levels are regulated by key 
tumorigenesis related genes such as TP53, RB1, MYC, JUN and CDKN2A. The 
biological functions of the genes could be associated with the essential steps 
necessary for tumor progression and metastasis, and cover the six well-defined 
hallmarks of cancer, reflecting the acquired malignant characteristics of a 
cancer cell along with tumor progression and metastasis-related biological 
activities.
CONCLUSION: Genes in the MammaPrint gene signature comprehensively measure the 
six hallmarks of cancer-related biology. This finding establishes a link between 
a molecular signature and the underlying molecular mechanisms of tumor cell 
progression and metastasis.