title: Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay.
abstract: BACKGROUND
  Diagnosis of basal-like breast cancer (BLBC) remains a bottleneck to conducting effective clinical trials for this aggressive subtype. We postulated that elevated expression of Forkhead Box transcription factor C1 (FOXC1) is a simple and accurate diagnostic biomarker for BLBC.
  
  
  METHODS
  Accuracy of FOXC1 expression in identifying BLBC was compared with the PAM50 gene expression panel in gene expression microarray (GEM) (n = 1992) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 349) datasets. A FOXC1-based immunohistochemical (IHC) assay was developed and assessed in 96 archival formalin-fixed, paraffin-embedded (FFPE) breast cancer samples that also underwent PAM50 profiling. All statistical tests were two-sided.
  
  
  RESULTS
  A FOXC1-based two-tier assay (IHC +/- qRT-PCR) accurately identified BLBC (AUC = 0.88) in an independent cohort of FFPE samples, validating the accuracy of FOXC1-defined BLBC in GEM (AUC = 0.90) and qRT-PCR (AUC = 0.88) studies, when compared with platform-specific PAM50-defined BLBC. The hazard ratio (HR) for disease-specific survival in patients having FOXC1-defined BLBC was 1.71 (95% CI = 1.31 to 2.23, P < .001), comparable to PAM50 assay-defined BLBC (HR = 1.74, 95% CI = 1.40 to 2.17, P < .001). FOXC1 expression also predicted the development of brain metastasis. Importantly, unlike triple-negative or Core Basal IHC definitions, a FOXC1-based definition is able to identify BLBC in both ER+ and HER2+ patients.
  
  
  CONCLUSIONS
  A FOXC1-based two-tier assay, by virtue of being rapid, simple, accurate, and cost-effective may emerge as the diagnostic assay of choice for BLBC. Such a test could substantially improve clinical trial enrichment of BLBC patients and accelerate the identification of effective chemotherapeutic options for this aggressive disease.
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Tor W
authors.initials: TW
authors.lastname: Jensen
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Tania
authors.initials: T
authors.lastname: Ray
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Wesley Y
authors.initials: WY
authors.lastname: Naritoku
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Bingchen
authors.initials: B
authors.lastname: Han
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Frank
authors.initials: F
authors.lastname: Bellafiore
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Sanjay P
authors.initials: SP
authors.lastname: Bagaria
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Annie
authors.initials: A
authors.lastname: Qu
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR).
authors.forename: Clive R
authors.initials: CR
authors.lastname: Taylor
authors.affiliation: : Interdisciplinary Health Sciences Initiative (TWJ, PSR), Department of Statistics (AQ), Beckman Institute for Advanced Science and Technology (PSR), University of Illinois Cancer Center (PSR), and Department of Surgery, University of Illinois College of Medicine (PSR), University of Illinois at Urbana Champaign, Urbana Champaign, IL; Onconostic Technologies, Inc., Champaign, IL (TR); John Wayne Cancer Institute, Santa Monica, CA (JW); Department of Pathology and Laboratory Medicine, Keck USC/LAC and USC Medical Center/VAGLAHS, Los Angeles, CA (XL, WYN); Departments of Surgery and Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA (BH, XC); Department of Pathology, Carle Foundation Hospital, Urbana, IL (FB); Department of Surgery, Mayo Clinic, Jacksonville, FL (SPB); Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CRT); Division of Surgical Oncology, Carle Cancer Center, Urbana, IL (PSR). psray@illinois.edu.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Ray
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000556:secondary; D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000737:chemistry / Q000175:diagnosis; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016707:Tissue Fixation / Q000379:methods; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D005557:Formaldehyde