title: ERRα Is a Marker of Tamoxifen Response and Survival in Triple-Negative Breast Cancer.
abstract: OBJECTIVE
  Estrogen-related receptor alpha (ERRα) signaling has recently been implicated in breast cancer. We investigated the clinical value of ERRα in randomized cohorts of tamoxifen-treated and adjuvant-untreated patients.
  
  
  METHODS
  Cox proportional hazards regression was used to evaluate the significance of associations between ERRα gene expression levels and patient DMFS in a previously published microarray dataset representing 2,000 breast tumor cases derived from multiple medical centers worldwide. The 912 tumors used for immunostaining were from a tamoxifen-randomized primary breast cancer trial conducted in Stockholm, Sweden, during 1976-1990. Mouse model was used to study the effect of tamoxifen treatment on lung colonization of MDA-MB-231 control cells and MDA-MB-231 cells with stable knockdown of ERRα. The phenotypic effects associated with ERRα modulation were studied using immunoblotting analyses and wound-healing assay.
  
  
  RESULTS
  We found that in ER-negative and triple-negative breast cancer (TNBC) adjuvant-untreated patients, ERRα expression indicated worse prognosis and correlated with poor outcome predictors. However, in tamoxifen-treated patients, an improved outcome was observed with high ERRα gene and protein expression. Reduced ERRα expression was oncogenic in the presence of tamoxifen, measured by in vitro proliferation and migration assays and in vivo metastasis studies.
  
  
  CONCLUSIONS
  Taken together, these data show that ERRα expression predicts response to tamoxifen treatment, and ERRα could be a biomarker of tamoxifen sensitivity and a prognostic factor in TNBC.
authors.affiliation: Department of Biology; Stern College for Women of Yeshiva University; New York, New York.
authors.forename: Subrata
authors.initials: S
authors.lastname: Manna
authors.affiliation: Department of Clinical and Experimental Medicine, and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Josefine
authors.initials: J
authors.lastname: Bostner
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina. The Comprehensive Cancer Center of Wake Forest University, Winston Salem, North Carolina.
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.affiliation: Department of Biology; Stern College for Women of Yeshiva University; New York, New York.
authors.forename: Anya
authors.initials: A
authors.lastname: Alayev
authors.affiliation: Department of Biology; Stern College for Women of Yeshiva University; New York, New York.
authors.forename: Naomi S
authors.initials: NS
authors.lastname: Schwartz
authors.affiliation: Department of Clinical and Experimental Medicine, and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Lager
authors.affiliation: Department of Oncology, Karolinska University Hospital, Stockholm South General Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Fornander
authors.affiliation: Department of Clinical and Experimental Medicine, and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nordenskjöld
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Department of Clinical and Experimental Medicine, and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
authors.affiliation: Department of Biology; Stern College for Women of Yeshiva University; New York, New York. Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, New York. Albert Einstein Cancer Center; Albert Einstein College of Medicine; Bronx, New York. mholz@yu.edu.
authors.forename: Marina K
authors.initials: MK
authors.lastname: Holz
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006801:Humans; D060787:Neoplasm Grading; D011379:Prognosis; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000097983:ERRalpha Estrogen-Related Receptor