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Clinicopathological Features of Triple-Negative Breast Cancer Epigenetic Subtypes.
Annals of surgical oncology : the official journal of the Society of Surgical Oncology
  • Maggie L DiNome
  • Javier I Orozco, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, USA
  • Chikako Matsuba, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Saint John's Health Center, Providence Health System, Santa Monica, California.
  • Ayla O Manughian-Peter, Department of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA
  • Miquel Ensenyat-Mendez
  • Shu-Ching Chang, Medical Data Research Center, Providence Health & Services, Portland, OR, USA
  • John R Jalas, Department of Pathology, Providence Saint John's Health Center, Santa Monica, CA, USA
  • Matthew P Salomon, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.
  • Diego M Marzese, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA
Document Type
Article
Publication Date
7-24-2019
Disciplines
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.

Clinical Institute
Cancer
Department
Oncology
Citation Information
Maggie L DiNome, Javier I Orozco, Chikako Matsuba, Ayla O Manughian-Peter, et al.. "Clinicopathological Features of Triple-Negative Breast Cancer Epigenetic Subtypes." Annals of surgical oncology : the official journal of the Society of Surgical Oncology (2019)
Available at: http://works.bepress.com/shu-ching-chang/50/