Clinical correlates of 'BRCAness' in triple-negative breast cancer of patients receiving adjuvant chemotherapy

Ann Oncol. 2012 Sep;23(9):2301-2305. doi: 10.1093/annonc/mdr621. Epub 2012 Feb 21.

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.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • BRCA1 Protein / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Docetaxel
  • Epirubicin / therapeutic use
  • Female
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Methotrexate / therapeutic use
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Young Adult

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF regimen
  • FEC protocol