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Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma

Kader, Tanjina; Hill, Prue; Zethoven, Magnus; Goode, David L.; Elder, Kenneth; Thio, Niko; Doyle, Maria; Semple, Timothy; Sufyan, Wajiha; Byrne, David J.; Pang, Jia-Min B.; Murugasu, Anand; Miligy, Islam M; Green, Andrew R; Rakha, Emad A; Fox, Stephen B.; Mann, G. Bruce; Campbell, Ian G.; Gorringe, Kylie L.

Authors

Tanjina Kader

Prue Hill

Magnus Zethoven

David L. Goode

Kenneth Elder

Niko Thio

Maria Doyle

Timothy Semple

Wajiha Sufyan

David J. Byrne

Jia-Min B. Pang

Anand Murugasu

Islam M Miligy

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology

Stephen B. Fox

G. Bruce Mann

Ian G. Campbell

Kylie L. Gorringe



Abstract

The current model for breast cancer progression proposes independent “low‐grade (LG) like” and “high‐grade (HG) like” pathways but lacks a known precursor to HG cancer. We applied low coverage whole genome sequencing to atypical ductal hyperplasia (ADH) with and without carcinoma to shed light on breast cancer progression. 14/20 isolated ADH cases harboured at least one copy number alteration (CNA), but had fewer aberrations than LG or HG ductal carcinoma in situ (DCIS). ADH carried more HG‐like CNA than LG DCIS (eg. 8q gain). Correspondingly, 64% (7/11) of ADH cases with synchronous HG carcinoma were clonally related, similar to LG carcinoma (67%, 6/9). This study represents a significant shift in our understanding of breast cancer progression, with ADH as a common precursor lesion to the independent “low‐grade like” and “high‐grade like” pathways. These data suggest that ADH can be a precursor of HG breast cancer and that LG and HG carcinomas can evolve from a similar ancestor lesion. We propose that although LG DCIS may be committed to a LG molecular pathway, ADH may remain multipotent, progressing to either LG or HG carcinoma. This multipotent nature suggests that some ADH could be more clinically significant than LG DCIS, requiring biomarkers for personalising management.

Citation

Kader, T., Hill, P., Zethoven, M., Goode, D. L., Elder, K., Thio, N., …Gorringe, K. L. (2019). Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma. Journal of Pathology, 248(3), 326-338. https://doi.org/10.1002/path.5262

Journal Article Type Article
Acceptance Date Mar 4, 2019
Online Publication Date Mar 6, 2019
Publication Date Mar 6, 2019
Deposit Date Mar 25, 2019
Publicly Available Date Mar 29, 2024
Journal The Journal of Pathology
Print ISSN 0022-3417
Electronic ISSN 1096-9896
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 248
Issue 3
Pages 326-338
DOI https://doi.org/10.1002/path.5262
Keywords atypical ductal hyperplasia; copy number; breast cancer progression; clonal; ductal carcinoma in situ; whole genome sequencing; pre?malignant breast lesions; benign breast disease
Public URL https://nottingham-repository.worktribe.com/output/1684811
Publisher URL https://onlinelibrary.wiley.com/doi/10.1002/path.5262