Unbiased Scientific Approach Yields Genomic Signature for Breast Cancer Recurrence

MammaPrint, initially known as the 70 Gene Amsterdam Signature, was originally developed as an academic/scientific endeavor using the best technology, the ideal tissue type and a whole genome approach to attain the optimal results.  The objective was to develop a gene expression signature that could accurately identify early stage breast cancer patients who were either at high risk or at low risk of recurrence and, therefore, enable more individualized treatment.

Development of the MammaPrint^® Profile

As published in Nature, MammaPrint was developed on 10 year outcome data from an untreated breast cancer patient population, thereby ensuring the validity of the results regardless of the ultimate treatment regimen selected. Moreover, both estrogen receptor positive and negative patients were included in the evaluation.

The MammaPrint genes were selected using an unbiased genome-wide approach in which all 25,000 genes in the human genome were evaluated to isolate the 231 most prognostic breast cancer-specific genes.  Using two-dimensional cluster analysis followed by a leave-one-out cross validation procedure, 70 critical genes were shown to best correlate with the likelihood of distant recurrence were determined and chosen for the MammaPrint profile. These 70 genes affect all steps known to be important for metastasis including cell cycle regulation, angiogenesis, invasion, cell migration and signal transduction.⁽²⁾

The resulting MammaPrint profile classifies tumors as either high risk or low risk of recurrence, and when used in conjunction with other risk factors, helps to identify patients who will benefit from adjuvant therapy.  Compared to standard risk assessment factors, MammaPrint significantly reduces the number of patients traditionally classified with a poor prognosis, while at the same time identifying those patients who may be at increased risk of recurrence despite their clinico-pathologic findings. Because MammaPrint uses gene expression profiling to analyze the gene activity of the tumor itself, it allows physicians to personalize treatment for each individual and in so doing improves quality of life for more patients.⁽³⁾