title: Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort and review.
abstract: OBJECTIVE
  The debate concerning poorer survival for patients with breast cancer (BC) carrying a BRCA1 germline mutation is unresolved, and requires additional data from population-based studies.
  
  
  METHODS
  We followed 232 women with invasive BC under age 46, ascertained prospectively through a French population-based BC registry and tested for BRCA1/2 mutations (median follow-up: 82 months). We compared tumour characteristics and survival rates between 21 BRCA1/2 deleterious mutation carriers and 211 non-carriers.
  
  
  RESULTS
  As compared to sporadic tumours, BRCA1/2 tumours showed higher grade (P = 0.02), fewer ductal carcinoma in situ (P = 0.02), more frequent medullary histology (P = 0.02), more frequent negative oestrogen and progesterone receptors (P = 0.001 each). At 5 years, BC-specific survival, metastasis-free survival, ipsilateral recurrence-free survival and contralateral BC-free survival rates for BRCA1/2 mutation carriers were 95.0%, 94.7%, 100% and 90.0% respectively, compared with 89.6%, 78.2%, 88.8% and 94.4% respectively, for non-carriers (not significant). Rates for women carrying only a BRCA1 mutation were 93.3%, 93.3%, 100%, 86.7%, respectively. 76% of BRCA1/2 carriers received chemotherapy.
  
  
  CONCLUSIONS
  Despite unfavourable tumour features, we found no evidence for poorer short-term survival in BRCA1 mutation carriers compared to non-carriers in this prospective population-based cohort. The high rate of BRCA1 carriers who received chemotherapy for their BC should question the positive impact of this treatment, as suggested by preclinical studies showing increased chemosensitivity of BRCA1-associated tumours.
authors.affiliation: Centre Léon Bérard, Unit of Prevention and Genetic Epidemiology, 28 rue Laënnec, 69 373 Lyon cedex 08, France. bonadona@lyon.fnclcc.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Bonadona
authors.forename: Sophie
authors.initials: S
authors.lastname: Dussart-Moser
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voirin
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
authors.forename: Hervé
authors.initials: H
authors.lastname: Mignotte
authors.forename: Patrice
authors.initials: P
authors.lastname: Mathevet
authors.forename: Alain
authors.initials: A
authors.lastname: Brémond
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.forename: Alain
authors.initials: A
authors.lastname: Martin
authors.forename: Pascale
authors.initials: P
authors.lastname: Romestaing
authors.forename: Daniel
authors.initials: D
authors.lastname: Raudrant
authors.forename: René-Charles
authors.initials: RC
authors.lastname: Rudigoz
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D002353:Carrier State; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis