title: Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry.
abstract: OBJECTIVE
  We examined borderline estrogen receptor (ER) -positive cancers, defined as having 1% to 10% positivity by immunohistochemistry (IHC), to determine whether they show the same global gene-expression pattern and high ESR1 mRNA expression as ER-positive cancers or if they are more similar to ER-negative cancers.
  
  
  METHODS
  ER status was determined by IHC in 465 primary breast cancers and with the Affymetrix U133A gene chip. We compared expressions of ESR1 mRNA and a 106 probe set ER-associated gene signature score between ER-negative (n = 183), 1% to 9% (n = 25), 10% (n = 6), and more than 10% (n = 251) ER-positive cancers. We also assessed the molecular class by using the PAM50 classifier and plotted survival by ER status.
  
  
  RESULTS
  Among the 1% to 9%, 10%, and more than 10% ER IHC-positive patients, 24%, 67%, and 92% were also positive by ESR1 mRNA expression. The average ESR1 expression was significantly higher in the ≥ 10% ER-positive cohorts compared with the 1% to 9% or ER-negative cohort. The average ER gene signature scores were similar for the ER-negative and 1% to 9% IHC-positive patients and were significantly lower than in ≥ 10% ER-positive patients. Among the 1% to 9% ER-positive patients, 8% were luminal B and 48% were basal-like; among the 10% ER-positive patients, 50% were luminal. The overall survival rate of 1% to 9% ER-positive patients with cancer was between those of patients in the ≥ 10% ER-positive and ER-negative groups.
  
  
  CONCLUSIONS
  A minority of the 1% to 9% IHC ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine-sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1439, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Daniel
authors.initials: D
authors.lastname: Booser
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: James L
authors.initials: JL
authors.lastname: Murray
authors.forename: Kimberly
authors.initials: K
authors.lastname: Koenig
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qi
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuoka
authors.forename: Elliana J
authors.initials: EJ
authors.lastname: Yang
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Christos
authors.initials: C
authors.lastname: Hatzis
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger