DNA methylation markers predict recurrence-free interval in triple-negative breast cancer

Mary Jo Fackler; Soonweng Cho; Leslie Cope; Edward Gabrielson; Kala Visvanathan; Kathleen Wilsbach; Danielle Meir-Levi; Charles F Lynch; Jeffrey Marks; Joseph Geradts; Meredith M Regan; Giuseppe Viale; Antonio C Wolff; Saraswati Sukumar; Christopher B Umbricht

doi:10.1038/s41523-020-0145-3

DNA methylation markers predict recurrence-free interval in triple-negative breast cancer

NPJ Breast Cancer. 2020 Jan 31:6:3. doi: 10.1038/s41523-020-0145-3. eCollection 2020.

Authors

Mary Jo Fackler¹, Soonweng Cho^{1

2}, Leslie Cope¹, Edward Gabrielson³, Kala Visvanathan^{1

4}, Kathleen Wilsbach^{2

3}, Danielle Meir-Levi¹, Charles F Lynch⁵, Jeffrey Marks⁶, Joseph Geradts^{7

8}, Meredith M Regan⁹, Giuseppe Viale¹⁰, Antonio C Wolff¹, Saraswati Sukumar^{1

3}, Christopher B Umbricht^{1

2

3}

Affiliations

¹ 1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
² 2Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
³ 3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
⁴ 4Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD 21205 USA.
⁵ SEER Tissue Repository Program, State Health Registry of Iowa, Iowa City, IA 52242 USA.
⁶ 6Department of Surgery, Duke University Medical Center, Durham, NC 27710 USA.
⁷ 7Department of Pathology, Duke University Medical Center, Durham, NC 27710 USA.
⁸ 8Department of Population Sciences, City of Hope National Medical Center, Duarte, CA 91010 USA.
⁹ 9IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215 USA.
¹⁰ 10Department of Pathology, IEO European Institute of Oncology IRCCS and University of Milan, Milan, Italy.

Abstract

We lack tools to risk-stratify triple-negative breast cancer (TNBC). Our goal was to develop molecular tools to predict disease recurrence. Methylation array analysis was performed on 110 samples treated by locoregional therapy obtained from institutional cohorts. Discovered marker sets were then tested by Kaplan-Meier analyses in a prospectively collected TNBC cohort of 49 samples from the no-chemotherapy arms of IBCSG trials VIII and IX, and by logistic regression in a chemotherapy-treated cohort of 121 TNBCs from combined IBCSG trials and institutional repositories. High methylation was associated with shorter recurrence-free interval in the no-chemotherapy arm of the IBCSG studies, as well as in the chemotherapy-treated patients within the combined institutional and IBCSG chemotherapy cohorts (100 marker panel, p = 0.002; 30 marker panel, p = 0.05). Chromosome 19 sites were enriched among these loci. In conclusion, our hypermethylation signatures identify increased recurrence risk independent of whether patients receive chemotherapy.

Keywords: Breast cancer; Prognostic markers.

Abstract

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