Abstract 5282: A 3q amplification gene signature associated with triple negative breast cancer lung-specific metastasis

Abstract

Abstract Triple negative breast cancers (TNBC), devoid of expression of the estrogen, progesterone and HER2 receptors, are among the most aggressive and deadly breast cancers, with high rates of tumor recurrence and metastatic spread. New prognostic markers are needed to identify patients who are at the highest risk for developing metastases, which might assist in tailoring treatment strategies. We previously identified 20 candidate driver genes in Chromosome 3q26-29, a critical amplified region in many human cancers including breast and lung cancer. The aim of this study was to assess the prognostic power of this 20-gene signature in TNBC patients. 855 breast tumors combined from four breast cancer cohorts (GSE12276, GSE2603, GSE2034 and NKI295) were used to evaluate the signature for prediction of organ-specific distant metastasis free survival (DMFS). The predictive ability of the 20-gene signature was evaluated by Cox proportional hazards model and was compared against other published breast cancer gene signatures including MammaPrint (70-gene), Veridex (76-gene), PAM50, 54 lung metastasis signature genes, HIF1 hypoxia pathway (8-gene), TGF β pathway (153-gene), BACH1 pathway metastasis gene signature (25-gene) and Gene Expression Prognostic Index Using Subtypes (GENIUS). The 20-gene signature was strongly associated with worse lung-specific metastasis-free survival (HR, 2.0, 95%CI, 1.4 to 2.87, P=0.00014) in TNBC patients (n = 131), independently of intrinsic subtype or published gene signatures and less so in non-TNBC patients (n = 724, HR, 1.3, 95%CI, 1.01 to 1.69, P=0.04). In conclusion, we discovered an amplified 20-gene signature in 3q26-29 that are associated with lung metastasis in patients with TNBC, suggesting on a potential role of 3q genes in the mechanism of lung-specific metastasis and incriminating cancer driver genes in this location as potential attractive novel therapeutic targets in this disease. The work is supported by the NIH Grant R01 CA102353 to PPM. Citation Format: Jun Qian, Heidi Chen, Pierre P. Massion. A 3q amplification gene signature associated with triple negative breast cancer lung-specific metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5282. doi:10.1158/1538-7445.AM2015-5282