title: BRCA mutations, molecular markers, and clinical variables in early-onset breast cancer: a population-based study.
abstract: Early age at onset is generally considered an indicator of genetic susceptibility to breast cancer. To address both the proportion of early-onset breast cancer associated with BRCA-1 or BRCA-2 germline mutation and the contribution of germline mutations to the clinical features and outcome of these tumors, we analyzed molecular status and clinical variables of a population-based sample of 66 Italian women diagnosed with breast cancer before the age of 40 who were unselected for family history. BRCA mutations were screened by automated sequencing of the entire BRCA-1 and BRCA-2 coding regions and splice junctions. Twenty-eight late-onset (over 45 years), sporadic, breast cancers were designated as "control group" for comparisons with early-onset cases. BRCA mutations (10 BRCA-1 and 6 BRCA-2) were detected in 15 (22.7%) out of 66 tested patients. The combination of ER, PR, HER-2/neu negativity and p53 positivity was significantly more frequent in BRCA-1 positive tumors than in BRCA-2 positive and non-BRCA tumors (P=0.03). Taken collectively, BRCA-positive tumors correlated with high histologic grade and ER negativity compared with non-BRCA and sporadic tumors (P=0.05 and 0.003, respectively). There were no significant differences between BRCA-associated breast cancers (BABC) and non-BABC in relapse-free, event-free, and overall survival. Our data confirm that the combination of age at onset and tumor phenotype can provide an efficient model for identifying individuals with a high probability of carrying BRCA mutations and support the hypothesis that breast cancer in BRCA carriers is qualitatively distinct from other early-onset breast cancers and from late-onset, sporadic, breast carcinomas. Further studies on incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, via Gramsci 14, 43100 Parma, Italy. antoninomusolino@hotmail.com <antoninomusolino@hotmail.com>
authors.forename: Antonino
authors.initials: A
authors.lastname: Musolino
authors.forename: Maria A
authors.initials: MA
authors.lastname: Bella
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bortesi
authors.forename: Maria
authors.initials: M
authors.lastname: Michiara
authors.forename: Nadia
authors.initials: N
authors.lastname: Naldi
authors.forename: Paola
authors.initials: P
authors.lastname: Zanelli
authors.forename: Marzia
authors.initials: M
authors.lastname: Capelletti
authors.forename: Debora
authors.initials: D
authors.lastname: Pezzuolo
authors.forename: Roberta
authors.initials: R
authors.lastname: Camisa
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
mesh_terms: D000328:Adult; D017668:Age of Onset; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; 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