Evaluating ZNF217 mRNA Expression Levels as a Predictor of Response to Endocrine Therapy in ER+ Breast Cancer

Abstract

<i>ZNF217</i> is a candidate oncogene with a wide variety of deleterious functions in breast cancer. Here, we aimed at investigating in a pilot prospective study the association between <i>ZNF217</i> mRNA expression levels and the clinical response to neoadjuvant endocrine therapy (ET) in postmenopausal ER-positive (ER+) breast cancer patients. Core surgical biopsy samples before treatment initiation and post-treatment were obtained from 68 patients, and Ki-67 values measured by immunohistochemistry (IHC) were used to identify responders (<i>n</i> = 59) and non-responders (<i>n</i> = 9) after 4 months of ET. We report for the first time that high <i>ZNF217</i> mRNA expression level measured by RT-qPCR in the initial tumor samples (pre-treatment) is associated with poor response to neoadjuvant ET. Indeed, the clinical positive response rate in patients with low <i>ZNF217</i> expression levels was significantly higher than that in those with high <i>ZNF217</i> expression levels (<i>P</i> = 0.027). Additionally, a retrospective analysis evaluating <i>ZNF217</i> expression levels in primary breast tumor of ER+/HER2-/LN0 breast cancer patients treated with adjuvant ET enabled the identification of poorer responders prone to earlier relapse (<i>P</i> = 0.013), while <i>ZNF217</i> did not retain any prognostic value in the ER+/HER2-/LN0 breast cancer patients who did not receive any treatment. Altogether, these data suggest that <i>ZNF217</i> expression might be predictive of clinical response to ET.