Predictions of breast cancer local and distant metastasis

A79

Breast tumor metastases pose the greatest threat to a patient's survival. Tumorigenesis is typically caused by genetic mutations and/or genomic instability while metastases are thought to be caused by gradual evolutionary events that occur after tumor formation and which impart new properties on the metastasis that are not present in the primary tumor. Based on this hypothesis, the target genes that drive metastasis might be different genes from those that cause carcinogenesis. We have created a dataset of breast tumors that includes primary tumors, local lymph node metastases and many distant metastases samples with clear molecular subtypes identified using a breast tumor "intrinsic" classification list. As expected, basal-like and HER2+/ER- subtypes exhibited a worse clinic outcome than most luminal tumors and were over-represented in the distant metastasis group.To better understand the molecular signatures of metastases, we used supervised analyses to compare three groups of tumors to each other: primary tumors without lymph node (LN) or distant metastases, tumors with lymph node metastases only and/or their LN metastasis samples, and distant metastasis samples and their primary tumors. When primary tumors without metastases were compared to primary tumors with lymph node metastases, very few if any, consistent differences were found and the cross validation rates were low; however, when no metastasis primary tumorsor local metastasis samples were compared to distant metastasis samples many significant differences were identified and cross validation rates were high (80%). In addition, we identified a 13-gene predictor that correlated with distant metastasis status that could be used to divide primary tumor only patients into low, intermediate, and high risk groups relative to overall survival. Further analysis of brain metastases alone also identified a distinct signature, which suggests that distant metastases are a distinct tumor group with unique biological properties.