K. Venetis (Milan, Italy)
IEO - Istituto Europeo di OncologiaAuthor Of 1 Presentation
10P - The clinical actionability of PTEN protein and gene expression analysis in HR- and HER2+ breast cancers
Abstract
Background
Phosphatase and tensin homologue (PTEN) loss is associated with tumorigenesis, tumor progression, and therapy resistance in breast cancer. However, the clinical value of PTEN as a biomarker requires further studies. We seek to identify clinically relevant subtypes of breast cancer based on PTEN status and other clinicopathologic features.
Methods
A cohort of 608 breast cancer patients previously profiled for PTEN protein expression was included. Based on the expression on the neoplastic cells compared to the normal internal controls by IHC, cases were classified as PTEN-low (PTEN-L) or PTEN-retained (PTEN-WT). The former constituted the study group, while the latter the control group. Analysis of gene expression was performed on 3,929 patients from the METABRIC and MSK cohorts retrieved from cBioPortal. The Shapiro-Wilk test was used to analyze the normal distributions of continuous variables. Relationships between PTEN status and the clinicopathologic and molecular features of the patient population were assessed using Fisher’s exact test or Chi-squared/Wilcoxon rank-sum test. Survival curves were built according to the Kaplan-Meier method.
Results
Reduced expression of PTEN was significantly different at protein and gene levels, where the former was observed in 46.1% (n=280/608), while, not surprisingly, the latter in only 7.8% (n=308/3,929) cases. PTEN-L tumors were significantly enriched for in both HER2+ (n=63, 22.5%) and triple-negative (TN) (n=41, 14.6%) subtypes compared to PTEN-WT tumors (n=34, 10.4% and n=18, 5.5%, respectively; p<0.0001). When the relative expression of PTEN was decreased, both hormone receptor (HR)- and HER2 overexpression/amplification were significantly related to worse overall survival (OS) compared to the HR+/HER2- status (p<.0001). Of note, this condition was not statistically significant in the presence of a PTEN-WT expression. Moreover, PTEN-L protein expression but not gene expression was related to worse OS in HR+/HER2+ tumors compared to HR+/HER2- (p=0.002).
Conclusions
The combined analysis of PTEN protein and gene expression may provide additional data to perform a tailored risk assessment while evaluating patients with HR- and HER2+ breast cancers.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Fusco: Speaker Bureau/Expert testimony: Merck Sharp & Dohme (MSD); Speaker Bureau/Expert testimony: Boehringer Ingelheim; Honoraria (self), Speaker Bureau/Expert testimony: Novartis. E. Guerini Rocco: Speaker Bureau/Expert testimony: Thermo Fisher Scientific; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Roche; Honoraria (self): MSD. All other authors have declared no conflicts of interest.