September 27, 2016
ADVANCE Distinguished Lecture Series presents William B. Coleman
The ADVANCE Distinguished Lecture Series and Sally Davis, assistant professor of diagnostic medicine and pathobiolgy, will host William B. Coleman, from the University of North Carolina School of Medicine, at 3:30 p.m. Sept. 29 in the Mara Conference Center on the fourth floor of Trotter Hall. Coleman will present "Molecular Signatures of Breast Cancer – Predicting Clinical Characteristics from Gene Expression Patterns."
Coleman's abstract: Breast cancer is a diverse collection of diseases that can be classified in various ways. We have evaluated the expression of gene expression signatures in a cohort of 855 breast cancers with known molecular subtype.
The signatures we have examined include:
1. The estrogen response signature, or ERS.
2. The p53 mutant/wild type signature — p53Mut/p53WT.
3. The aberrant DNA hypermethylation-associated signature — hypermethylator/non-hypermethylator.
The estrogen response signature provides a measure of the intactness of the estrogen response pathway. Kaplan-Meier analysis of relapse-free survival, RFS, revealed a statistically significant advantage for patients with ERS+ breast cancers, and a significant improvement in RFS among ERS+ breast cancers that received hormone therapy versus untreated.
The p53 mutation status signature provides an indication of the intactness of p53 pathways and may be an effective surrogate for p53 mutation status. P53Mut breast cancers progress to metastatic disease more often than p53WT breast cancers with a shorter time to progression contributing to a RFS disadvantage. Patients with p53WT breast cancers benefit from chemotherapy, whereas patients with p53Mut breast cancers do not. These results suggest strongly that knowing the ERS status and p53 mutation status can benefit patients with breast cancer by guiding treatment decisions, ensuring appropriately aggressive treatment.
The aberrant DNA hypermethylation signature identifies breast cancers that express a hypermethylator phenotype with concurrent methylation-dependent silencing of numerous genes. Expression of the hypermethylator signature confers a RFS disadvantage. Compared to non-hypermethylators, breast cancers expressing the hypermethylator signature progress to metastatic disease more frequently and with a shorter disease-free interval. Expression of the aberrant DNA hypermethylation signature appears to associate with ER-negative breast cancers — most basal-like and claudin-low breast cancers express the aberrant DNA hypermethylation signature. These results suggest strongly that patients with breast cancers expressing the aberrant DNA hypermethylation signature are more aggressive than those that do not and may benefit from epigenetic therapy targeting aberrant DNA hypermethylation.