Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay

Tor W. Jensen, Tania Ray, Jinhua Wang, Xiaodong Li, Wesley Y. Naritoku, Bingchen Han, Frank Bellafiore, Sanjay P. Bagaria, Annie Qu, Xiaojiang Cui, Clive R. Taylor, Partha S. Ray

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32 Scopus citations

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. Conclusion: 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.

Original languageEnglish (US)
Article numberdjv148
JournalJournal of the National Cancer Institute
Volume107
Issue number8
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Jensen, T. W., Ray, T., Wang, J., Li, X., Naritoku, W. Y., Han, B., Bellafiore, F., Bagaria, S. P., Qu, A., Cui, X., Taylor, C. R., & Ray, P. S. (2015). Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay. Journal of the National Cancer Institute, 107(8), [djv148]. https://doi.org/10.1093/jnci/djv148