Aurora kinase A as a possible marker for endocrine resistance in early estrogen receptor positive breast cancer

Abstract

Background: Cell culture studies have disclosed that the mitotic Aurora kinase A is causally involved in both tamoxifen and aromatase inhibitor resistant cell growth and thus may be a potential new marker for endocrine resistance in the clinical setting.

Material and methods: Archival tumor tissue was available from 1323 Danish patients with estrogen receptor (ER) positive primary breast cancer, who participated in the Breast International Group (BIG) 1-98 trial, comparing treatment with tamoxifen and letrozole and both in a sequence. The expression of Aurora A was determined by immunohistochemistry in 980 tumors and semi quantitively scored into three groups; negative/weak, moderate and high. The Aurora A expression levels were compared to other clinico-pathological parameters and outcome, defined as disease-free survival (DFS) and overall survival (OS).

Results: High expression of Aurora A was found in 26.9% of patients and moderate in 57.0%. High expression was significantly associated with high malignancy grade and HER2 amplification. High Aurora A expression was significantly more frequent in ductal compared to lobular carcinomas. We found no significant association between Aurora A expression and DFS or OS and no evidence of interaction between Aurora A expression and benefits from tamoxifen versus letrozole.

Conclusions: Aurora A expression in breast tumors was associated with high malignancy grade III and with HER2 amplification. A trend as a prognostic factor for OS was found in patients with high Aurora A expression. No predictive property was observed in this study with early breast cancer.

Acknowledgments

We kindly acknowledge the participating patients, investigators, study nurses and thank the Danish Pathology Departments for supplying paraffin embedded tumor material: Aalborg Sygehus, Aarhus Hospital, Bispebjerg Hospital, Esbjerg Sygehus, Gentofte Hospital, Herlev Hospital, Hillerød Hospital, Hjørring Sygehus, Holstebro Sygehus, Hvidovre Hospital, Nykøbing Falster sygehus, Naestved Sygehus, Odense Hospital, Randers Sygehus, Rigshospitalet, Roskilde Sygehus, Skive Sygehus, Slagelse Sygehus, Svendborg Sygehus, Sønderborg Sygehus, Vejle Sygehus and Viborg Sygehus. Thanks to Annette Bartels and Nils Brünner from Section for Molecular Disease Biology, University of Copenhagen for the help rendered regarding immunohistochemical analysis.

Disclosure statement

No potential conflicts of interest were disclosed.

Additional information

Funding

This study was supported by Danish Cancer Society, grant no. R72-A4510-13-S2.