title: Clinical correlates of 'BRCAness' in triple-negative breast cancer of patients receiving adjuvant chemotherapy.
abstract: BACKGROUND
  We have previously reported an array comparative genomic hybridization profile that identifies triple-negative breast cancers (TNBC), with BRCA1 dysfunction and a high sensitivity to intensified dose bifunctional alkylating agents. To determine the effect of conventional-dose chemotherapy in patients with this so-called BRCA1-like profile, clinical characteristics and survival were studied in a large group of TNBC patients.
  
  
  METHODS
  DNA was isolated and BRCA1-like status was assessed in 101 patients with early-stage TNBC receiving adjuvant cyclophosphamide-based chemotherapy. Clinical characteristics and survival were compared between BRCA1-like and non-BRCA1-like groups. Results Sixty-six tumors (65%) had a BRCA1-like profile. Patients with BRCA1-like tumors tended to be younger and had more often node-negative disease (P = 0.06 and P = 0.03, respectively). Five-year recurrence-free survival was 80% for the BRCA1-like group and 75% for the non-BRCA1-like group (P = 0.35). T stage was the only variable significantly associated with survival.
  
  
  CONCLUSIONS
  BRCA1-like tumors share clinical features, like young age at diagnosis and similar nodal status, with breast cancers in BRCA1 mutation carriers. Their prognosis is similar to that of non-BRCA1-like tumors when conventional-dose chemotherapy is administered. TNBCs that are classified as BRCA1-like may contain a defect in homologous recombination and could, in theory, benefit from the addition of poly ADP ribose polymerase inhibitors.
authors.affiliation: Departments of Medical Oncology.
authors.forename: A M M
authors.initials: AMM
authors.lastname: Oonk
authors.affiliation: Pathology, Deventer Hospital, Deventer.
authors.forename: C
authors.initials: C
authors.lastname: van Rijn
authors.affiliation: Pathology, Deventer Hospital, Deventer.
authors.forename: M M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Departments of Experimental Therapy; Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam.
authors.forename: L
authors.initials: L
authors.lastname: Mulder
authors.affiliation: MRC-Holland, Amsterdam.
authors.forename: N
authors.initials: N
authors.lastname: Laddach
authors.affiliation: MRC-Holland, Amsterdam.
authors.forename: S P
authors.initials: SP
authors.lastname: Savola
authors.affiliation: Departments of Experimental Therapy; Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam.
authors.forename: J
authors.initials: J
authors.lastname: Wesseling
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: s.rodenhuis@nki.nl.
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.affiliation: Departments of Medical Oncology.
authors.forename: A L T
authors.initials: ALT
authors.lastname: Imholz
authors.affiliation: Departments of Experimental Therapy; Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam.
authors.forename: E H
authors.initials: EH
authors.lastname: Lips
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C492913:BRCA1 protein, human; C508053:ERBB2 protein, human