title: Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options.
abstract: Triple negative breast cancers are a heterogeneous group of tumors characterized by poor patient survival and lack of targeted therapeutics. Androgen receptor has been associated with triple negative breast cancer pathogenesis, but its role in the different subtypes has not been clearly defined. We examined androgen receptor protein expression by immunohistochemical analysis in 678 breast cancers, including 396 triple negative cancers. Fifty matched lymph node metastases were also examined. Association of expression status with clinical (race, survival) and pathological (basal, non-basal subtype, stage, grade) features was also evaluated. In 160 triple negative breast cancers, mRNA microarray expression profiling was performed, and differences according to androgen receptor status were analyzed. In triple negative cancers the percentage of androgen receptor positive cases was lower (24.8% vs 81.6% of non-triple negative cases), especially in African American women (16.7% vs 25.5% of cancers of white women). No significant difference in androgen receptor expression was observed in primary tumors vs matched metastatic lesions. Positive androgen receptor immunoreactivity was inversely correlated with tumor grade (p<0.01) and associated with better overall patient survival (p = 0.032) in the non-basal triple negative cancer group. In the microarray study, expression of three genes (HER4, TNFSF10, CDK6) showed significant deregulation in association with androgen receptor status; eg CDK6, a novel therapeutic target in triple negative cancers, showed significantly higher expression level in androgen receptor negative cases (p<0.01). These findings confirm the prognostic impact of androgen receptor expression in non-basal triple negative breast cancers, and suggest targeting of new androgen receptor-related molecular pathways in patients with these cancers.
authors: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors: Pierluigi
authors: P
authors: Gasparini
authors: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, United States of America ; ARC-NET Research Centre, University and Hospital Trust of Verona, Verona Italy.
authors: Matteo
authors: M
authors: Fassan
authors: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors: Luciano
authors: L
authors: Cascione
authors: Department of Pathology, Hacettepe University, Ankara Turkey.
authors: Gulnur
authors: G
authors: Guler
authors: Department of Pathology, Hacettepe University, Ankara Turkey.
authors: Serdar
authors: S
authors: Balci
authors: Department of Pathology, Hacettepe University, Ankara Turkey.
authors: Cigdem
authors: C
authors: Irkkan
authors: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors: Carolyn
authors: C
authors: Paisie
authors: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors: Francesca
authors: F
authors: Lovat
authors: Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors: Carl
authors: C
authors: Morrison
authors: Bioinformatics Shared Resource, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
authors: Jianying
authors: J
authors: Zhang
authors: ARC-NET Research Centre, University and Hospital Trust of Verona, Verona Italy.
authors: Aldo
authors: A
authors: Scarpa
authors: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors: Carlo M
authors: CM
authors: Croce
authors: Division of Medical Oncology and the Breast Program, James Cancer Hospital and Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors: Charles L
authors: CL
authors: Shapiro
authors: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors: Kay
authors: K
authors: Huebner
mesh_terms: D000328:Adult; D000368:Aged; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D011944:Receptors, Androgen / Q000032:analysis* / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen