The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma

Tanjina Kader; Kenneth Elder; Magnus Zethoven; Timothy Semple; Prue Hill; David L Goode; Niko Thio; Dane Cheasley; Simone M Rowley; David J Byrne; Jia-Min Pang; Islam M Miligy; Andrew R Green; Emad A Rakha; Stephen B Fox; G Bruce Mann; Ian G Campbell; Kylie L Gorringe

doi:10.1038/s41523-020-0150-6

The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma

NPJ Breast Cancer. 2020 Mar 12:6:9. doi: 10.1038/s41523-020-0150-6. eCollection 2020.

Authors

Tanjina Kader^{1

2}, Kenneth Elder³, Magnus Zethoven¹, Timothy Semple¹, Prue Hill⁴, David L Goode^{1

2}, Niko Thio¹, Dane Cheasley¹, Simone M Rowley¹, David J Byrne¹, Jia-Min Pang¹, Islam M Miligy⁵, Andrew R Green⁵, Emad A Rakha⁵, Stephen B Fox¹, G Bruce Mann³, Ian G Campbell^#^{1

2

6}, Kylie L Gorringe^#^{1

2

6}

Affiliations

¹ 1Peter MacCallum Cancer Centre, Melbourne, VIC Australia.
² 2The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC Australia.
³ 3The Breast Service, The Royal Women's Hospital, Fitzroy, VIC Australia.
⁴ 4Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, VIC Australia.
⁵ 5Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, UK.
⁶ 6Department of Clinical Pathology, University of Melbourne, Parkville, VIC Australia.

^# Contributed equally.

Abstract

Intraductal papillomas (IDP) are challenging breast findings because of their variable risk of progression to malignancy. The molecular events driving IDP development and genomic features of malignant progression are poorly understood. In this study, genome-wide CNA and/or targeted mutation analysis was performed on 44 cases of IDP, of which 20 cases had coexisting ductal carcinoma in situ (DCIS), papillary DCIS or invasive ductal carcinoma (IDC). CNA were rare in pure IDP, but 69% carried an activating PIK3CA mutation. Among the synchronous IDP cases, 55% (11/20) were clonally related to the synchronous DCIS and/or IDC, only one of which had papillary histology. In contrast to pure IDP, PIK3CA mutations were absent from clonal cases. CNAs in any of chromosomes 1, 16 or 11 were significantly enriched in clonal IDP lesions compared to pure and non-clonal IDP. The observation that 55% of IDP are clonal to DCIS/IDC indicates that IDP can be a direct precursor for breast carcinoma, not limited to the papillary type. The absence of PIK3CA mutations and presence of CNAs in IDP could be used clinically to identify patients at high risk of progression to carcinoma.

Keywords: Breast cancer; Cancer genetics.