TY - JOUR
T1 - Aurora kinase A as a possible marker for endocrine resistance in early estrogen receptor positive breast cancer
AU - Lykkesfeldt, Anne E
AU - Iversen, Benedikte R
AU - Jensen, Maj-Britt
AU - Ejlertsen, Bent
AU - Giobbie-Hurder, Anita
AU - Reiter, Birgit E
AU - Kirkegaard, Tove
AU - Rasmussen, Birgitte B
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
KW - Antineoplastic Agents, Hormonal/therapeutic use
KW - Aromatase Inhibitors/therapeutic use
KW - Aurora Kinase A/metabolism
KW - Biomarkers/metabolism
KW - Breast Neoplasms/metabolism
KW - Carcinoma, Ductal, Breast/metabolism
KW - Carcinoma, Lobular/metabolism
KW - Denmark/epidemiology
KW - Disease-Free Survival
KW - Drug Resistance, Neoplasm
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - Letrozole
KW - Nitriles/therapeutic use
KW - Prognosis
KW - Receptor, ErbB-2/metabolism
KW - Receptors, Estrogen/metabolism
KW - Tamoxifen/therapeutic use
KW - Triazoles/therapeutic use
U2 - 10.1080/0284186X.2017.1404126
DO - 10.1080/0284186X.2017.1404126
M3 - Article
C2 - 29202611
SN - 0284-186X
VL - 57
SP - 67
EP - 73
JO - Acta Oncologica
JF - Acta Oncologica
IS - 1
ER -