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

Abstract

© 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.

Citation

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. https://doi.org/10.1038/s41416-019-0436-3

• 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
• DOI: https://doi.org/10.1038/s41416-019-0436-3
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/1737449
• Publisher URL: https://www.nature.com/articles/s41416-019-0436-3
• 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).
• Contract Date: Apr 4, 2019