The Society of Surgical Oncology, inc.
The American Society of Breast Surgeons.
Annals of Surgical Oncology

Log in | Register

Clinicopathological Features of Triple-Negative Breast Cancer Epigenetic Subtypes

Maggie L. DiNome MD, Javier I. J. Orozco MD, Chikako Matsuba PhD, Ayla O. Manughian-Peter MSc, Miquel Ensenyat-Mendez MSc, Shu-Ching Chang PhD, John R. Jalas MD, Matthew P. Salomon PhD, Diego M. Marzese PhD
Breast Oncology
Volume 26, Issue 10 / October , 2019

Abstract

Background/Objective

Triple-negative breast cancer (TNBC) is a heterogeneous collection of breast tumors with numerous differences including morphological characteristics, genetic makeup, immune-cell infiltration, and response to systemic therapy. DNA methylation profiling is a robust tool to accurately identify disease-specific subtypes. We aimed to generate an epigenetic subclassification of TNBC tumors (epitypes) with utility for clinical decision-making.

Methods

Genome-wide DNA methylation profiles from TNBC patients generated in the Cancer Genome Atlas project were used to build machine learning-based epigenetic classifiers. Clinical and demographic variables, as well as gene expression and gene mutation data from the same cohort, were integrated to further refine the TNBC epitypes.

Results

This analysis indicated the existence of four TNBC epitypes, named as Epi-CL-A, Epi-CL-B, Epi-CL-C, and Epi-CL-D. Patients with Epi-CL-B tumors showed significantly shorter disease-free survival and overall survival [log rank; P = 0.01; hazard ratio (HR) 3.89, 95% confidence interval (CI) 1.3–11.63 and P = 0.003; HR 5.29, 95% CI 1.55–18.18, respectively]. Significant gene expression and mutation differences among the TNBC epitypes suggested alternative pathway activation that could be used as ancillary therapeutic targets. These epigenetic subtypes showed complementarity with the recently described TNBC transcriptomic subtypes.

Conclusions

TNBC epigenetic subtypes exhibit significant clinical and molecular differences. The links between genetic make-up, gene expression programs, and epigenetic subtypes open new avenues in the development of laboratory tests to more efficiently stratify TNBC patients, helping optimize tailored treatment approaches.

Add a comment



0 comment(s)

ANNALS ON SOCIAL MEDIA

@AnnSurgOncol 

Join the conversation!

Follow the journal on Twitter and Facebook

Help to expand the reach of the journal to support the research and practice needs of surgical oncologists and their patients.