TY - JOUR
T1 - Basal-like breast cancer defined by FOXC1 expression offers superior prognostic value
T2 - A retrospective immunohistochemical study
AU - Ray, Partha S.
AU - Bagaria, Sanjay P.
AU - Wang, Jinhua
AU - Shamonki, Jaime M.
AU - Ye, Xing
AU - Sim, Myung Shin
AU - Steen, Shawn
AU - Qu, Ying
AU - Cui, Xiaojiang
AU - Giuliano, Armando E.
N1 - Funding Information:
ACKNOWLEDGMENT P.S.R., S.P.B., J.W., and X.C. are named inventors on patent applications filed relevant to the role of FOXC1 in cancer. This work was supported by funding from QVC and the Fashion Footwear Association of New York Charitable Foundation, the Associates for Breast and Prostate Cancer Studies, the John Wayne Cancer Foundation, and the Avon Foundation. We thank Drs. John Martens and Silvana Martino for critical reading of the article.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
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U2 - 10.1245/s10434-011-1657-8
DO - 10.1245/s10434-011-1657-8
M3 - Article
C2 - 21424368
AN - SCOPUS:82955236210
SN - 1068-9265
VL - 18
SP - 3839
EP - 3847
JO - Annals of surgical oncology
JF - Annals of surgical oncology
IS - 13
ER -