The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution
Menée à partir d'une biopuce comportant des échantillons tumoraux prélevés sur 868 patientes atteintes d'un carcinome canalaire in situ du sein (CCIS) et/ou d'un cancer mammaire invasif, cette étude détermine le statut HER2 des CCIS ainsi que les caractéristiques clinico-pathologiques associées, puis évalue l'association entre la surexpression de HER2 et le pronostic
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.
British Journal of Cancer , résumé, 2019