title: Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers.
abstract: BACKGROUND
  BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness characteristics frequencies in a large cohort of triple-negative breast cancers (TNBCs).
  
  
  METHODS
  As a measure of BRCAness, we determined a specific BRCA1-like pattern by array Comparative Genomic Hybridisation (aCGH), and BRCA1 promoter methylation in 377 TNBCs, obtained from 3 different patient cohorts. Clinicopathological data were available for all tumours, BRCA1-germline mutation status and chemotherapy response data were available for a subset.
  
  
  RESULTS
  Of the tumours, 66-69% had a BRCA1-like aCGH profile and 27-37% showed BRCA1 promoter methylation. BRCA1-germline mutations and BRCA1 promoter methylation were mutually exclusive events (P=1 × 10(-5)). BRCAness was associated with younger age and grade 3 tumours. Chemotherapy response was significantly higher in BRCA1-mutated tumours, but not in tumours with BRCAness (63% (12 out of 19) vs 35% (18 out of 52) pathological complete remission rate, respectively).
  
  
  CONCLUSIONS
  The majority of the TNBCs show BRCAness, and those tumours share clinicopathological characteristics with BRCA1-mutated tumours. A better characterisation of TNBC and the presence of BRCAness could have consequences for both hereditary breast cancer screening and the treatment of these tumours.
authors.affiliation: Department of Molecular Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Lips
authors.forename: L
authors.initials: L
authors.lastname: Mulder
authors.forename: A
authors.initials: A
authors.lastname: Oonk
authors.forename: L E
authors.initials: LE
authors.lastname: van der Kolk
authors.forename: F B L
authors.initials: FB
authors.lastname: Hogervorst
authors.forename: A L T
authors.initials: AL
authors.lastname: Imholz
authors.forename: J
authors.initials: J
authors.lastname: Wesseling
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: P M
authors.initials: PM
authors.lastname: Nederlof
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
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