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

Abstract

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.

• Authors: Islam M Miligy, Michael S Toss, Kylie L Gorringe, Andrew H S Lee, Ian O Ellis, Andrew R Green, Emad A Rakha
• Journal: British journal of cancer (Br J Cancer) Vol. 120 Issue 11 Pg. 1075-1082 (05 2019) ISSN: 1532-1827 [Electronic] England
• PMID: 31065110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Breast Neoplasms (chemistry, pathology)
• Carcinoma, Intraductal, Noninfiltrating (chemistry, pathology)
• Female
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Receptor, ErbB-2 (analysis, genetics)
• Retrospective Studies
• Tissue Array Analysis