Abstract P2-05-22: Prognostic significance of nuclear factor kappa B in node-negative breast cancer is most pronounced in luminal B breast cancer

Abstract

Abstract Background: The importance of the cellular as well as the humoral immune system is increasingly recognized in breast cancer. The transcription factor nuclear factor kappa B (NFKB1) plays an important role in immune cell development. We examined the prognostic significance of NFKB1 in node-negative breast cancer. Methods: Microarray based gene-expression data for NFKB1 (209239_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Intrinsic subtypes were determined using gene-expression data. Prognostic significance of NFKB1 for metastasis-free survival (MFS) was examined in the whole cohort, in estrogen receptor (ER) positive as well as ER negative patients, and in different intrinsic subtypes: luminal A, liminal B, basal-like, HER2-enriched (HER2-E), and normal-like. Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of NFKB1 was related to better MFS in a meta-analysis of the whole cohort (HR 0.48, 95% CI 0.34-0.67, P<0.0001). NFKB1 was significantly associated with MFS only in ER positive (HR 0.41, 95% CI 0.24−0.69, P=0.0008) but not in ER negative (HR 0.76, 95% CI 0.39−1.48, P=0.4245) patients. Regarding intrinsic subtypes, the prognostic significance of NFKB1 was most pronounced in luminal B breast cancer (HR 0.40, 95% CI 0.17−0.93, P=0.0338) as compared to luminal A (HR 0.67, 95% CI 0.16−2.73, P=0.5738), basal-like (HR 0.67, 95% CI 0.29−1.56), P=0.3484), HER2-E (HR 0.70, 95% CI 0.25−2.00, P=0.5083), and normal-like (HR 0.49, 95% CI 0.18−1.32, P=0.1579) breast cancer. However, NFKB1 failed to show independent prognostic significance (HR 0.72, 95% CI 0.42-1.24, P=0.235) in multivariate analysis. Only histological grade of differentiation (HR 2.06, 95% CI 1.27-3.35, P=0.003) and tumor size (HR 1.58, 95% CI 1.01-2.48, P=0.045), but neither age nor HER2 status nor hormone receptor status maintained an independent prognostic association with MFS. Conclusions: The transcription factor NFKB1 shows prognostic significance in node-negative breast cancer. Higher expression of NFKB1 is associated with improved outcome. The prognostic impact of NFKB1 differs between intrinsic subtypes and is most pronounced in luminal B breast cancer. Citation Format: Schmidt M, Madjar K, Heimes A-S, Battista M, Lebrecht A, Almsetdt K, Hasenburg A, Rahnenführer J, Hengstler JG. Prognostic significance of nuclear factor kappa B in node-negative breast cancer is most pronounced in luminal B breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-22.