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The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution

Miligy, Islam M.; Toss, Michael S.; Gorringe, Kylie L.; Lee, Andrew H.S.; Ellis, Ian O.; Green, Andrew R.; Rakha, Emad


Islam M. Miligy

Kylie L. Gorringe

Andrew H.S. Lee

Professor of Breast Cancer Pathology


© 2019, Cancer Research UK. Background: Previous studies have reported up to 50% of ductal carcinoma in situ (DCIS), is HER2 positive, but the frequency of HER2-positive invasive breast cancer (IBC) is lower. The aim of this study is to characterise HER2 status in DCIS and assess its prognostic value. Methods: HER2 status was evaluated in a large series of DCIS (n = 868), including pure DCIS and DCIS associated with IBC, prepared as tissue microarrays (TMAs). HER2 status was assessed using immunohistochemistry (IHC) and chromogenic in situ hybridisation (CISH). Results: In pure DCIS, HER2 protein was over-expressed in 9% of DCIS (3+), whereas 15% were HER2 equivocal (2+). Using CISH, the final HER2 status was positive in 20%. In mixed DCIS, HER2 amplification of the DCIS component was detected in 15% with amplification in the invasive component of only 12%. HER2-positive DCIS was associated with features of aggressiveness (p < 0.0001) and more frequent local recurrence (p = 0.03). On multivariate analysis, combined HER2+/Ki67+ profile was an independent predictor of local recurrence (p = 0.006). Conclusions: The frequency of HER2 positivity in DCIS is comparable to IBC- and HER2-positive DCIS is associated with features of poor prognosis. The majority of HER2 over-expression in DCIS is driven by gene amplification.


Miligy, I. M., Toss, M. S., Gorringe, K. L., Lee, A. H., Ellis, I. O., Green, A. R., & Rakha, E. (2019). The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution. British Journal of Cancer, 120(11), 1075-1082.

Journal Article Type Article
Acceptance Date Mar 7, 2019
Online Publication Date May 8, 2019
Publication Date May 8, 2019
Deposit Date Apr 4, 2019
Publicly Available Date Nov 9, 2019
Journal British Journal of Cancer
Print ISSN 0007-0920
Electronic ISSN 1532-1827
Publisher Cancer Research UK
Peer Reviewed Peer Reviewed
Volume 120
Issue 11
Pages 1075-1082
Keywords Cancer Research; Oncology
Public URL
Publisher URL
Additional Information Received: 8 September 2018; Revised: 4 March 2019; Accepted: 7 March 2019; First Online: 8 May 2019; : The authors declare that they have no competing interests.; : This work obtained ethics approval by the North West – Greater Manchester Central Research Ethics Committee under the title; Nottingham Health Science Biobank (NHSB), reference number 15/NW/068; : The authors confirm the data that has been used in this work is available on reasonable request.; : This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).