title: RNA-based determination of ESR1 and HER2 expression and response to neoadjuvant chemotherapy.
abstract: BACKGROUND
  Hormone and human epidermal growth factor receptor 2 (HER2) receptors are the most important breast cancer biomarkers, and additional objective and quantitative test methods such as messenger RNA (mRNA)-based quantitative analysis are urgently needed. In this study, we investigated the clinical validity of RT-PCR-based evaluation of estrogen receptor (ESR1) and HER2 mRNA expression.
  
  
  METHODS
  A total of 1050 core biopsies from two retrospective (GeparTrio, GeparQuattro) and one prospective (PREDICT) neoadjuvant studies were evaluated by quantitative RT-PCR for ESR1 and HER2.
  
  
  RESULTS
  ESR1 mRNA was significantly predictive for reduced response to neoadjuvant chemotherapy in univariate and multivariate analysis in all three cohorts. The complete pathologically documented response (pathological complete response, pCR) rate for ESR1+/HER2- tumors was 7.3%, 8.0% and 8.6%; for ESR1-/HER2- tumors it was 34.4%, 33.7% and 37.3% in GeparTrio, GeparQuattro and PREDICT, respectively (P < 0.001 in each cohort). In the Kaplan-Meier analysis in GeparTrio patients with ESR1+/HER2- tumors had the best prognosis, compared with ESR1-/HER2- and ESR1-/HER2+ tumors [disease-free survival (DFS): P < 0.0005, overall survival (OS): P < 0.0005].
  
  
  CONCLUSIONS
  Our results suggest that mRNA levels of ESR1 and HER2 predict response to neoadjuvant chemotherapy and are significantly associated with long-term outcome. As an additional option to standard immunohistochemistry and gene-array-based analysis, quantitative RT-PCR analysis might be useful for determination of the receptor status in breast cancer.
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, D-10117 Berlin. carsten.denkert@charite.de
authors.forename: C
authors.initials: C
authors.lastname: Denkert
authors.forename: S
authors.initials: S
authors.lastname: Loibl
authors.forename: R
authors.initials: R
authors.lastname: Kronenwett
authors.forename: J
authors.initials: J
authors.lastname: Budczies
authors.forename: C
authors.initials: C
authors.lastname: von Törne
authors.forename: V
authors.initials: V
authors.lastname: Nekljudova
authors.forename: S
authors.initials: S
authors.lastname: Darb-Esfahani
authors.forename: C
authors.initials: C
authors.lastname: Solbach
authors.forename: B V
authors.initials: BV
authors.lastname: Sinn
authors.forename: C
authors.initials: C
authors.lastname: Petry
authors.forename: B M
authors.initials: BM
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Hilfrich
authors.forename: G
authors.initials: G
authors.lastname: Altmann
authors.forename: A
authors.initials: A
authors.lastname: Staebler
authors.forename: C
authors.initials: C
authors.lastname: Roth
authors.forename: B
authors.initials: B
authors.lastname: Ataseven
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C506487:ESR1 protein, human; C508053:ERBB2 protein, human