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

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

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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.

Original language	English (US)
Article number	3
Journal	npj Breast Cancer
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41523-020-0145-3
State	Published - Dec 1 2020

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Pharmacology (medical)

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Fackler, M. J., Cho, S., Cope, L., Gabrielson, E., Visvanathan, K., Wilsbach, K., Meir-Levi, D., Lynch, C. F., Marks, J., Geradts, J., Regan, M. M., Viale, G., Wolff, A. C., Sukumar, S., & Umbricht, C. B. (2020). DNA methylation markers predict recurrence-free interval in triple-negative breast cancer. npj Breast Cancer, 6(1), Article 3. https://doi.org/10.1038/s41523-020-0145-3

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title = "DNA methylation markers predict recurrence-free interval in triple-negative breast cancer",

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.",

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

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doi = "10.1038/s41523-020-0145-3",

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AU - Fackler, Mary Jo

AU - Cho, Soonweng

AU - Cope, Leslie

AU - Gabrielson, Edward

AU - Visvanathan, Kala

AU - Wilsbach, Kathleen

AU - Meir-Levi, Danielle

AU - Lynch, Charles F.

AU - Marks, Jeffrey

AU - Geradts, Joseph

AU - Regan, Meredith M.

AU - Viale, Giuseppe

AU - Wolff, Antonio C.

AU - Sukumar, Saraswati

AU - Umbricht, Christopher B.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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

Abstract

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