title: Molecular profile and clinical variables in BRCA1-positive breast cancers. A population-based study.
abstract: OBJECTIVE
  To evaluate the clinical features of breast cancer patients with genetic susceptibility to this disease and to investigate the contribution of BRCA1 germline mutations to the phenotype of these tumors.
  
  
  METHODS
  We reviewed the clinical and pathological records of 102 women with suspected inherited susceptibility to breast cancer consecutively seen at the Genetic Oncology Service of Parma, Italy. Sixty-two patients with a high probability of harboring a germline, cancer-predisposing mutation were tested for BRCA1 mutations. Exon 11 was screened using the protein truncation test and detected mutations were confirmed by direct sequencing (DS). All other exons were analyzed by DS.
  
  
  RESULTS
  Among the 62 patients with a completed mutation analysis, 48 (77.4%) had wild-type BRCA1, six (9.6%) had variants of unclear significance, eight (13%) had deleterious mutations. BRCA1-associated breast cancers (BABC) were significantly less likely to be diagnosed at stage I than breast cancers in women without mutations (12.5% vs 51%; P = 0.045), more likely to have a high proliferation rate (100% vs 24%, P < 0.001), and more likely to be histological grade 3 (100% vs 14%, P < 0.001), estrogen and progesterone receptor negative (87.5% vs 13%, P < 0.001; 75% vs 23%, P = 0.004), and p53 positive (87.5% vs 30%, P = 0.023). All tumors with BRCA1 mutations were HER-2/neu negative compared with 57% of the non-BRCA1 tumors (P = 0.04). There were no significant differences between BABC and non-BABC in 20-year relapse-free survival, 20-year event-free survival, and 20-year overall survival.
  
  
  CONCLUSIONS
  In this population-based study, BABC seems to present with adverse molecular features when compared with non-BABC, although the prognosis appears to be similar.
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43100 Parma, Italy. antoninomusolino@hotmail.com
authors.forename: Antonino
authors.initials: A
authors.lastname: Musolino
authors.forename: Maria
authors.initials: M
authors.lastname: Michiara
authors.forename: Maria A
authors.initials: MA
authors.lastname: Bella
authors.forename: Nadia
authors.initials: N
authors.lastname: Naldi
authors.forename: Paola
authors.initials: P
authors.lastname: Zanelli
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bortesi
authors.forename: Marzia
authors.initials: M
authors.lastname: Capelletti
authors.forename: Linda
authors.initials: L
authors.lastname: Soldani
authors.forename: Roberta
authors.initials: R
authors.lastname: Camisa
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martella
authors.forename: Vittorio
authors.initials: V
authors.lastname: Franciosi
authors.forename: Mario
authors.initials: M
authors.lastname: Savi
authors.forename: Tauro M
authors.initials: TM
authors.lastname: Neri
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53