title: FOXC1 identifies basal-like breast cancer in a hereditary breast cancer cohort.
abstract: 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.
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Dadmanesh
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Bingchen
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu-Rice
authors.affiliation: Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bagaria
authors.affiliation: Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Clive
authors.initials: C
authors.lastname: Taylor
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.|Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.|Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Farin
authors.initials: F
authors.lastname: Amersi
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.|Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018295:Neoplasms, Basal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010793:Phthalazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib
keywords: BRCA; FOXC1; PARP inhibitor; basal-like breast cancer; immunohistochemistry