TY - JOUR
T1 - FOXC1 identifies basal-like breast cancer in a hereditary breast cancer cohort
AU - Johnson, Jeff
AU - Choi, Michael
AU - Dadmanesh, Farnaz
AU - Han, Bingchen
AU - Qu, Ying
AU - Yu-Rice, Yi
AU - Zhang, Xiao
AU - Bagaria, Sanjay
AU - Taylor, Clive
AU - Giuliano, Armando E.
AU - Amersi, Farin
AU - Cui, Xiaojiang
N1 - Funding Information:
X.C. is supported by National Institutes of Health (CA151610), the Avon Foundation (02-2014-063), Eleanor and Glenn Padnick Discovery Fund in Cellular Therapy, and David Salomon Translational Breast Cancer Research Fund, and the Entertainment Industry Foundation. Giuliano is supported by the Fashion Footwear Charitable Foundation of New York, Inc., Associates for Breast and Prostate Cancer Studies, and the Margie and Robert E. Petersen Foundation. The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
PY - 2016
Y1 - 2016
N2 - Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1 and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or luminal breast cancer, respectively. BLBC is an aggressive subtype of breast cancer associated with liver and lung metastases and poorer prognosis than other subtypes and for which chemotherapy is the only systemic therapy. Multiple immunohistochemical markers are used to identify the basal-like subtype, including the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2. Forkhead box C1 (FOXC1) has been identified as a specific marker expressed in BLBC in general breast cancer cohorts. We examined an institutional cohort of breast cancer patients with germline BRCA1 (n=46) and BRCA2 (n=35) mutations and found that FOXC1 expression on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations [30/46 vs. 6/35]. In BRCA1 mutant tumors, FOXC1 was expressed in 28/31 BLBC tumors and 2/13 non-BLBC tumors, In BRCA2 mutant tumors, FOXC1 was expressed in 5/5 BLBC tumors and 1/30 non-BLBC tumors. In cell culture models of BRCA1-mutant breast cancer, FOXC1 is associated with increased proliferation and may serve as a marker for sensitivity to PARP-inhibitor therapy with olaparib.
AB - Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1 and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or luminal breast cancer, respectively. BLBC is an aggressive subtype of breast cancer associated with liver and lung metastases and poorer prognosis than other subtypes and for which chemotherapy is the only systemic therapy. Multiple immunohistochemical markers are used to identify the basal-like subtype, including the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2. Forkhead box C1 (FOXC1) has been identified as a specific marker expressed in BLBC in general breast cancer cohorts. We examined an institutional cohort of breast cancer patients with germline BRCA1 (n=46) and BRCA2 (n=35) mutations and found that FOXC1 expression on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations [30/46 vs. 6/35]. In BRCA1 mutant tumors, FOXC1 was expressed in 28/31 BLBC tumors and 2/13 non-BLBC tumors, In BRCA2 mutant tumors, FOXC1 was expressed in 5/5 BLBC tumors and 1/30 non-BLBC tumors. In cell culture models of BRCA1-mutant breast cancer, FOXC1 is associated with increased proliferation and may serve as a marker for sensitivity to PARP-inhibitor therapy with olaparib.
KW - BRCA
KW - Basal-like breast cancer
KW - FOXC1
KW - Immunohistochemistry
KW - PARP inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84996629618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84996629618&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.12370
DO - 10.18632/oncotarget.12370
M3 - Article
C2 - 27708239
AN - SCOPUS:84996629618
SN - 1949-2553
VL - 7
SP - 75729
EP - 75738
JO - Oncotarget
JF - Oncotarget
IS - 46
ER -