title: ERβ1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer.
abstract: BACKGROUND
  The role and clinical value of ERβ1 expression is controversial and recent data demonstrates that many ERβ antibodies are insensitive and/or non-specific. Therefore, we sought to comprehensively characterize ERβ1 expression across all sub-types of breast cancer using a validated antibody and determine the roles of this receptor in mediating response to multiple forms of endocrine therapy both in the presence and absence of ERα expression.
  
  
  METHODS
  Nuclear and cytoplasmic expression patterns of ERβ1 were analyzed in three patient cohorts, including a retrospective analysis of a prospective adjuvant tamoxifen study and a triple negative breast cancer cohort. To investigate the utility of therapeutically targeting ERβ1, we generated multiple ERβ1 expressing cell model systems and determined their proliferative responses following anti-estrogenic or ERβ-specific agonist exposure.
  
  
  RESULTS
  Nuclear ERβ1 was shown to be expressed across all major sub-types of breast cancer, including 25% of triple negative breast cancers and 33% of ER-positive tumors, and was associated with significantly improved outcomes in ERα-positive tamoxifen-treated patients. In agreement with these observations, ERβ1 expression sensitized ERα-positive breast cancer cells to the anti-cancer effects of selective estrogen receptor modulators (SERMs). However, in the absence of ERα expression, ERβ-specific agonists potently inhibited cell proliferation rates while anti-estrogenic therapies were ineffective.
  
  
  CONCLUSIONS
  Using a validated antibody, we have confirmed that nuclear ERβ1 expression is commonly present in breast cancer and is prognostic in tamoxifen-treated patients. Using multiple breast cancer cell lines, ERβ appears to be a novel therapeutic target. However, the efficacy of SERMs and ERβ-specific agonists differ as a function of ERα expression.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Reese
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Malayannan
authors.initials: M
authors.lastname: Subramaniam
authors.forename: Xianglin
authors.initials: X
authors.lastname: Wu
authors.forename: Vivian
authors.initials: V
authors.lastname: Negron
authors.forename: Anne
authors.initials: A
authors.lastname: Gingery
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Pitel
authors.forename: Sejal S
authors.initials: SS
authors.lastname: Shah
authors.forename: Heather E
authors.initials: HE
authors.lastname: Cunliffe
authors.forename: Ann E
authors.initials: AE
authors.lastname: McCullough
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Pockaj
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.forename: Carol
authors.initials: C
authors.lastname: Reynolds
authors.forename: Wilma L
authors.initials: WL
authors.lastname: Lingle
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Spelsberg
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Goetz
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, 16-01B Guggenheim Building, 200 First St, SW, Rochester, MN 55905, USA. hawse.john@mayo.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Hawse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D013629:Tamoxifen