Phosphorylated ERα, HIF-1α, and MAPK signaling as predictors of primary endocrine treatment response and resistance in patients with breast cancer

Abstract

Purpose: We aimed to identify signaling pathways involved in the response and resistance to aromatase inhibitor therapy in patients with breast cancer. Patients and Methods: One hundred fourteen women with T2-4 N0-1, estrogen receptor (ER) α-positive tumors were randomly assigned to neoadjuvant letrozole or letrozole plus metronomic cyclophosphamide. Twenty-four tumor proteins involved in apoptosis, cell survival, hypoxia, angiogenesis, growth factor, and hormone signaling were assessed by immunohistochemistry in pretreatment samples (eg, caspase 3, phospho- mammalian target of rapamycin, hypoxia-inducible factor 1α [HIF-1α], vascular endothelial growth factor, mitogen-activated protein kina..