Abstract
BackgroundBreast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone3 Lysine27 tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. In BC patients, lower H3K27me3 expression has been associated with worse prognosis. We assessed H3K27me3 immunoexpression with digital imaging software assistance, in a cohort of luminal-like BC patients with long-term follow-up time and evaluated its association with clinically relevant endpoints and its clinical usefulness.MethodsH3K27me3 immunoexpression was assessed, by means of digital-imaging system, in archival tissue samples of 160 luminal A/B-like HER2-negative invasive BC, stages I-III. Survival analysis was performed using Kaplan-Meier and Cox regression. Cases were categorized as ‘low’ or ‘high’ expression based on cut-off defined by receiver operating characteristic (ROC) curve analysis.ResultsThe patient cohort showed a median age of 61-years, with a median follow-up time of 11.7 years. Low H3K27me3 expression (below 85% cut-off) was significantly associated with recurrence, both in univariable (HR = 1.99, 95%CI 1.066–3.724) and multivariable analysis when adjusting for grade and age (HR = 1.89, 95%CI 1.004–3.559). A trend for higher risk of death in low H3K27me3 expression BC was observed (p = 0.069), reaching statistical significance in younger patients (p = 0.021).ConclusionsH3K27me3 immunoexpression assessed by digital imaging scoring software is an independent prognosis biomarker in luminal-like BC patients and may assist in more individualized adjuvant treatment decisions, thus potentially reducing recurrences after curative-intent treatment, while sparing unnecessary toxicity.
Highlights
Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes
Retrospective analysis previously performed in clinical samples suggested that lower H3K27me3 expression was associated with worse prognosis in those patients, and H3K27me3 was considered a promising therapeutic target (Ribrag et al 2015; Takeshima et al 2015; Ko et al 2016; Yan et al 2017; Taube et al 2017)
In this exploratory retrospective study that included 160 invasive BC patients with a median 10-year-plus follow-up, it was found that lower expression of H3K27me3 negatively impacts on prognosis, predicting lower Disease-free survival (DFS) and increased likelihood of recurrence and endocrine resistance, especially in luminal Blike BC
Summary
Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone Lysine tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. Epigenetics, i.e. gene expression alterations without changes in DNA sequence (Egger et al 2004), include histone post-translational modifications, which may have distinct roles in cancer biology (Lan et al 2007; Sauvageau and Sauvageau 2010). Trimethylation of lysine 27 of histone 3 (H3K27me3) is amongst those modifications and is related to Polycomb Repressive Complexes 2 (PRC2). Retrospective analysis previously performed in clinical samples suggested that lower H3K27me expression was associated with worse prognosis in those patients, and H3K27me was considered a promising therapeutic target (Ribrag et al 2015; Takeshima et al 2015; Ko et al 2016; Yan et al 2017; Taube et al 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
