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

Abstract

ZNF217 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 ZNF217 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 (n = 59) and non-responders (n = 9) after 4 months of ET. We report for the first time that high ZNF217 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 ZNF217 expression levels was significantly higher than that in those with high ZNF217 expression levels (P = 0.027). Additionally, a retrospective analysis evaluating ZNF217 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 (P = 0.013), while ZNF217 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 ZNF217 expression might be predictive of clinical response to ET.

Keywords: ZNF217; breast cancer; clinical response; endocrine therapy; predictive biomarker.

FIGURE 1

High ZNF217 mRNA expression levels are associated with poor neoadjuvant ET response. (A) Dot plot representing ZNF217 mRNA expression levels in the initial breast tumors of responders or non-responders. Medians and 95% confidence intervals are shown for each group. (B) Changes in the Ki-67 expression for patients in the initial tumor and post-treatment tumor according to the mRNA expression levels of ZNF217. Red lines correspond to the non-responders (displaying increased ΔKi-67). (C) Receiver operating characteristic (ROC) curve for ZNF217 mRNA expression levels. AUC, area under curve.

FIGURE 2

High ZNF217 mRNA expression levels are associated with earlier relapse for patients treated with ET only. Kaplan-Meier analyses for relapse-free survival (RFS) are shown for ER+/HER2–/LN0 breast cancer patients (A) treated with adjuvant ET only and (B) who did not receive any treatment.