The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples

James E. Barrett, Chiara Herzog, Allison Jones, Olivia C. Leavy, Iona Evans, Susanne Knapp, Daniel Reisel, Tatiana Nazarenko, Yoo-Na Kim, Dorella Franchi, Andy Ryan, Joanna Franks, Line Bjørge, Michal Zikan, David Cibula, Nadia Harbeck, Nicoletta Colombo, Frank Dudbridge, Louise Jones, Karin Sundström, Joakim Dillner, Angelique Flöter Rådestad, Kristina Gemzell-Danielsson, Nora Pashayan and Martin Widschwendter ()
Additional contact information
James E. Barrett: Universität Innsbruck, Innsbruck
Chiara Herzog: Universität Innsbruck, Innsbruck
Allison Jones: University College London
Olivia C. Leavy: University of Leicester
Iona Evans: University College London
Susanne Knapp: University College London
Daniel Reisel: University College London
Tatiana Nazarenko: University College London
Yoo-Na Kim: Universität Innsbruck, Innsbruck
Dorella Franchi: Istituto Europeo di Oncologia, IRCCS
Andy Ryan: University College London
Joanna Franks: Breast Service, University College London Hospital
Line Bjørge: Haukeland University Hospital
Michal Zikan: First Faculty of Medicine, Charles University in Prague, University Hospital Bulovka
David Cibula: Charles University in Prague, General University Hospital in Prague
Nadia Harbeck: University of Munich (LMU)
Nicoletta Colombo: Istituto Europeo di Oncologia, IRCCS
Frank Dudbridge: University of Leicester
Louise Jones: Barts Cancer Institute, Queen Mary University of London
Karin Sundström: Division of Pathology, Karolinska Institutet
Joakim Dillner: Division of Pathology, Karolinska Institutet
Angelique Flöter Rådestad: Karolinska Institutet and Karolinska University Hospital
Kristina Gemzell-Danielsson: Karolinska Institutet and Karolinska University Hospital
Nora Pashayan: University College London
Martin Widschwendter: Universität Innsbruck, Innsbruck

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women’s risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80–0.88) and 0.81 (95% CI: 0.76–0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.

Date: 2022
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DOI: 10.1038/s41467-021-27918-w

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