Clinicopathological Features of Triple-Negative Breast Cancer Epigenetic Subtypes

被引:15
作者
DiNome, Maggie L. [1 ]
Orozco, Javier I. J. [2 ]
Matsuba, Chikako [3 ]
Manughian-Peter, Ayla O. [2 ]
Ensenyat-Mendez, Miquel [4 ]
Chang, Shu-Ching [5 ]
Jalas, John R. [6 ]
Salomon, Matthew P. [3 ]
Marzese, Diego M. [2 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA
[2] Providence St Johns Hlth Ctr, John Wayne Canc Inst, Canc Epigenet Lab, Santa Monica, CA 90401 USA
[3] Providence St Johns Hlth Ctr, John Wayne Canc Inst, Computat Biol Lab, Santa Monica, CA USA
[4] Balearic Isl Hlth Res Inst IdISBa, Canc Cell Biol Grp, Palma De Mallorca, Islas Baleares, Spain
[5] Providence St Joseph Hlth, Med Data Res Ctr, Portland, OR USA
[6] Providence St Johns Hlth Ctr, Dept Pathol, Santa Monica, CA USA
关键词
METHYLATION-BASED CLASSIFICATION; GROWTH; MULTICENTER; SYSTEM; TOOL;
D O I
10.1245/s10434-019-07565-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3344 / 3353
页数:10
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