Abstract P3-06-20: A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers (TNBCs) who receive adjuvant chemotherapy following curative surgery of the primary breast cancer

Abstract

Abstract BACKGROUND: Women with triple-negative breast cancers (TNBCs) represent a significant treatment challenge as they have a relatively poor prognosis and no effective targeted therapy exists. Although TNBCs are often discussed as a single disease entity of breast cancers, in fact they are very heterogeneous. The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate TNBCs among patients, who received adjuvant chemotherapy after curative surgery, into those with high or low risk for distant recurrence. METHODS: We tested whether the results of a NanoString expression assay that targeted 245 prospectively selected genes and used mRNA extracted from paraffin wax-embedded tumor tissues would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). RESULTS: NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63, and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis in this patients’ cohort and were validated with cross-validation. The proportions of patients categorized as having low or high risk were 75% and 25%, respectively. The Kaplan–Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% (95% CI, 48.6–78.9%) and 85% (95% confidence interval, CI, 79.2–90.7%), respectively. When adjusting for tumor–node–metastasis (TNM) stage, the distant recurrence-free survival (DRFS)s in the low-risk groups were significantly longer than that in the high-risk group (p<.001) in each of TNM stages I plus II, and III. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system. CONCLUSION: A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy. Citation Format: Yeon Hee Park, Hae Hyun Jung, In-Gu Do, Eun Yoon Cho, Insuk Sohn, Sin-Ho Jung, Won Ho Kil, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im. A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers (TNBCs) who receive adjuvant chemotherapy following curative surgery of the primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-20.