RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response. Cell Cycle 2010 Oct 15;9(20):4153-63
Date
10/16/2010Pubmed ID
20948315Pubmed Central ID
PMC3055199DOI
10.4161/cc.9.20.13454Scopus ID
2-s2.0-77958510718 (requires institutional sign-in at Scopus site) 147 CitationsAbstract
In breast cancer, inactivation of the RB tumor suppressor gene is believed to occur via multiple mechanisms to facilitate tumorigenesis. However, the prognostic and predictive value of RB status in disease-specific clinical outcomes has remained uncertain. We investigated RB pathway deregulation in the context of both ER-positive and ER-negative disease using combined microarray datasets encompassing over 900 breast cancer patient samples. Disease-specific characteristics of RB pathway deregulation were investigated in this dataset by evaluating correlation among pathway genes as well as differential expression across patient tumor populations defined by ER status. Survival analysis among these breast cancer samples demonstrates that the RB-loss signature is associated with poor disease outcome within several independent cohorts. Within the ER-negative subpopulation, the RB-loss signature is associated with improved response to chemotherapy and longer relapse-free survival. Additionally, while individual genes in the RB target signature closely reproduce its prognostic value, they also serve to predict and monitor response to therapeutic compounds, such as the cytostatic agent PD-0332991. These results indicate that the RB-loss signature expression is associated with poor outcome in breast cancer, but predicts improved response to chemotherapy based on data in ER-negative populations. While the RB-loss signature, as a whole, demonstrates prognostic and predictive utility, a small subset of markers could be sufficient to stratify patients based on RB function and inform the selection of appropriate therapeutic regimens.
Author List
Ertel A, Dean JL, Rui H, Liu C, Witkiewicz AK, Knudsen KE, Knudsen ESMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsBreast Neoplasms
Databases, Genetic
Disease-Free Survival
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Oligonucleotide Array Sequence Analysis
Prognosis
Receptors, Estrogen
Retinoblastoma Protein
Signal Transduction
Treatment Outcome
