Abstract P5-08-13: NDRG1 expression is an independent prognostic factor in inflammatory breast cancer
Authors: Villodre Emilly Schlee , Gong Yun , Hu Xiaoding , Huo Lei , Yoon Esther C , Ueno Naoto T , Woodward Wendy A , Tripathy Debu , Song Juhee , Debeb Bisrat G 
Published: March 2022

Abstract
Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive form of breast cancer. Patients with IBC still have worse clinical outcomes compared to patients with non-IBC (40% versus 63% for 5 years overall survival, respectively) despite advances in breast cancer treatment. IBC remains a poorly characterized disease lacking specific therapeutic targets and prognostic biomarkers. Our group demonstrated that N-myc downstream regulated gene 1 (NDRG1) is crucial in promoting tumorigenesis and brain metastasis in mouse models of IBC. Our hypothesis is that NDRG1 is a prognostic marker associated with poor outcome in IBC patients. Methods: 64 IBC patients in a tissue microarray were evaluated by immunohistochemical staining with anti-NDRG1 primary antibody and NDRG1 levels were quantified. Using the median value, 32 patients were grouped as NDRG1-low (≤ median), and 32 as NDRG1-high (&gt;median). Survival data were compared by Kaplan–Meier curves and log-rank test. Results: The average age of patients was 50 years. Sixty-two percent of patients had estrogen receptor (ER)-negative tumors, 83% were stage III, 80% high grade, and 67% of these patients received adjuvant radiation. The median follow-up time for the patients studied was 11.7 years, and the median overall survival (OS) time was 3.7 years. On univariate analysis, NDRG1 expression, tumor grade, disease stage, ER status, and adjuvant radiation therapy were associated with OS and disease specific survival (DSS). Patients with NDRG1-low tumors experienced better actuarial 10-year OS (p=0.0129) and DSS (p=0.0074), and showed significant higher 10-year OS and DSS rates than patients with NDRG1-high(OS, 45% vs. 19%, p=0.0278; DSS, 52% vs. 22%, p=0.0139). The median OS and DSS times were shorter for NDRG1-high patients (OS, 2.5 years; DSS, 3.1 years) than for NDRG1-low patients (OS, 5.9 years; DSS, 10.7 years). Multivariable analysis, NDRG1 was an independent predictor of OS (hazard ratio [HR]=2.449, p=0.0274) and DSS (HR=2.727, p=0.0039). ER status, disease stage and adjuvant radiation were also independent predictor for both OS and DSS. Furthermore, we observed that NDRG1-high expressing ER-negative tumors exhibit worse outcome in IBC patients (OS, p=0.0003; DSS, p=0.0003). NDRG1-high expression correlated with worse outcome in patients that received adjuvant radiation treatment (OS, p=0.0088; DSS, p=0.0093), and those with stage III (OS, p=0.0450; DSS, p=0.0239). Conclusions: Our findings demonstrated that NDRG1 is positively correlated with aggressive tumor characteristics in IBC and that it is an independent prognostic factor for OS and DSS in IBC patients, suggesting that targeting NDRG1 may provide a novel therapeutic strategy to improve outcomes for patients with IBC. Our data further suggests that NDRG1 warrants further investigation in radiation response.
Citation Format: Emilly Schlee Villodre, Yun Gong, Xiaoding Hu, Lei Huo, Esther C Yoon, Naoto T Ueno, Wendy A Woodward, Debu Tripathy, Juhee Song, Bisrat G Debeb. NDRG1 expression is an independent prognostic factor in inflammatory breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-13.