BioProject

The prognosis of a patient with Estrogen Receptor (ER) and/or Progesterone Receptor (PR)-positive breast cancer is highly variable. More...

The prognosis of a patient with Estrogen Receptor (ER) and/or Progesterone Receptor (PR)-positive breast cancer is highly variable. Therefore, we developed a gene-expression based outcome predictor for ER+ and/or PR+ (i.e. Luminal) breast cancer patients using biological properties of the tumors. First, we identified estrogen-regulated genes using the ER+ MCF-7 breast cancer cell line treated with estrogen. The estrogen-induced gene set was then used to hierarchically cluster a training set of 65 ER+ and/or PR+ tumors into 2 group, which showed survival differences (p=0.0004). Next, supervised analyses based upon these two groups was performed and identified 822 genes that optimally defined these two groups, with the poor prognosis Group IIE tumors showing a proliferation signature and high expression of anti-apoptosis genes and the good outcome Group IE showing the high expression of estrogen and GATA3-induced genes. Centroids were created for each group and applied to ER+ and/or PR+ tumors from three published datasets. For all datasets, Kaplan-Meier survival analyses showed a statistically significant difference in Relapse-Free Survival (and Overall) between Group IE and IIE tumors. Multivariate Cox analysis of the largest test dataset also showed that this predictor was adding independent information. This study provides new biological information concerning differences within Luminal/ER+ breast cancers and a means of predicting long term outcomes in ER+ and/or PR+ breast cancer patients. Keywords: other Overall design: cell lines Vs. Tumors Less...