title: Basal-like breast cancer defined by FOXC1 expression offers superior prognostic value: a retrospective immunohistochemical study.
abstract: BACKGROUND
  Basal-like breast cancer (BLBC) has a poor prognosis and is often identified by the triple-negative phenotype (TNP) and/or basal cytokeratins (CKs). Overexpression of mRNA for forkhead box C1 (FOXC1) transcription factor was recently identified as a pivotal prognostic biomarker of BLBC. We investigated the prognostic value of FOXC1 protein expression in invasive breast cancer and compared its prognostic significance to that of TNP and basal CKs.
  
  
  METHODS
  Archived TNP specimens of primary invasive ductal breast cancer from 759 patients were examined by immunohistochemical staining for FOXC1, CK5/6, and CK14; prognostic significance was assessed using multivariate analyses. In addition, the impact of adding FOXC1 versus basal CKs to TNP-based BLBC assessment was assessed.
  
  
  RESULTS
  FOXC1 protein expression was a significant predictor of overall survival on univariate (hazard ratio [HR] 3.364 95% confidence interval [CI] 1.758-6.438, P = 0.0002) and multivariate (HR 3.389 95% CI 1.928-7.645, P = 0.0001) analyses, despite its correlation with younger age (P = 0.0003). Interestingly, nodal status was not significant on multivariate analysis when FOXC1 expression status was included in the analysis. BLBC defined by TNP plus FOXC1 demonstrated superior prognostic relevance compared to BLBC defined by TNP or TNP plus basal CKs.
  
  
  CONCLUSIONS
  Immunohistochemical detection of FOXC1 expression in TNP invasive breast cancer is an independent prognostic indicator that is superior to conventional immunohistochemical surrogates of BLBC. Prospective validation is warranted to further define the diagnostic, prognostic, and predictive utility of FOXC1 in breast cancer management and clinical trial design.
authors.affiliation: Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA, USA.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Ray
authors.forename: Sanjay P
authors.initials: SP
authors.lastname: Bagaria
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Shamonki
authors.forename: Xing
authors.initials: X
authors.lastname: Ye
authors.forename: Myung-Shin
authors.initials: MS
authors.lastname: Sim
authors.forename: Shawn
authors.initials: S
authors.lastname: Steen
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C112743:FOXC1 protein, human