title: A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy.
abstract: Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival. The 3q gene signature was strongly associated with lung metastasis only in TNBC (P < 0.0001, Hazard ratio (HR) 1.44, 95% confidence interval (CI), 1.31-1.60), significantly associated with brain but not bone metastasis regardless of TNBC status. The association of one 3q driver gene FXR1 with distant metastasis in TNBC (P = 0.01) was further validated by immunohistochemistry. In addition, the 3q gene signature was associated with better response to neoadjuvant chemotherapy in TNBC (P < 0.0001) but not in non-TNBC patients. Our study suggests that the 3q gene signature is a novel prognostic marker for lung and/or brain metastasis and a predictive marker for the response to neoadjuvant chemotherapy in TNBC, implying a potential role for 3q genes in the mechanism of organ-specific metastasis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Vanderbilt Center for Quantitative Sciences, Department of Statistics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Rosana
authors.initials: R
authors.lastname: Eisenberg
authors.affiliation: Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: A Bapsi
authors.initials: AB
authors.lastname: Chakravarthy
authors.affiliation: Divsion of Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Mayer
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.|Veterans Affairs Medical Center, Nashville, TN, USA.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C096916:FXR1 protein, human; D016601:RNA-Binding Proteins