Differentiation Score and Intrinsic Subtype Predict Breast Cancer Organ of Relapse

ABSTRACT: The ability to predict metastatic potential is of clinical and biological importance. Numerous metastasis/relapse predictors exist for breast cancer patients; however, what is less well established is whether predicting metastasis to specific organs sites is feasible. In this study we sought to determine: 1) the degree to which gene signatures vary across tumors and their metastases, 2) if genomic intrinsic subtypes associate with particular organs of relapse, and 3) if other genomic signatures can predict spread to specific organs. Using a gene expression microarray data set of >1000 breast tumors and metastases, we observed that >90% of 298 gene signatures were similarly expressed between matched pairs of breast tumors and metastases; those most altered were reflective of cell types including fibroblasts and immune cells. Significant associations were identified between tumor subtypes and organ of first relapse. Among these, HER2-enriched tumors were significantly associated with liver, and Basal-like and Claudin-low tumors with brain and lung. Correspondingly, previously published brain and lung metastasis signatures, along with embryonic stem cell and tumor initiating cell signatures, were also associated with Basal-like and Claudin-low subtypes. These signatures strongly correlated with low Differentiation Scores (DS) and, to a lesser extent, high proliferation. Interestingly, within Basal-like and Claudin-low tumors, low DS further predicted for brain and lung metastases. In total, intrinsic subtype and DS provide clinically useful information that identifies the distant organ sites that should be most closely monitored for signs of disease recurrence. 414 samples profiled on Agilent microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Harrell JC 

PROVIDER: S-ECPF-GEOD-26338 | biostudies-other | 2012 Apr

REPOSITORIES: biostudies-other