title: Early onset breast cancer in Ashkenazi women carriers of founder BRCA1/2 mutations: beyond 10 years of follow-up.
abstract: This study uncovers disease characteristics by long-term follow-up in Ashkenazi early onset breast cancer (EOBC) patients, carriers of founder BRCA1/2 mutations compared to non-carriers of such mutations. An archives-retrospective design was conducted to study the pathological and clinical characteristics of 149 Ashkenazi Jewish EOBC patients (<42 years) who were referred consecutively to the oncogenetic clinic by the oncology centre at Rambam HealthCare Campus, as from 1995, with a mean follow-up of 13.61 years. Of 149 patients, 33 (22.1%) and 15 (10.1%) carried the founder BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) mutations, respectively; and 101 (67.8%) were non-carriers of these mutations. Contralateral breast-cancer was predominant among BRCA1/2 carriers compared to non-carriers (14, 58.3%; 6, 60%; 7, 8.1%; respectively, p < .001). Ovarian cancer was diagnosed in two BRCA1 carriers and one non-carrier. Oestrogen and/or progesterone receptor negative tumours were majorly detected in BRCA1 carriers (n = 16, 57.1%) compared to BRCA2 carriers (n = 4, 30.8%) and non-carriers (n = 23, 25.3%) (p = .007). BRCA1 carriers and non-carriers developed contralateral breast cancer at an earlier age than BRCA2 carriers. BRCA2 carriers portrayed similar tumour characteristics to non-carriers. EOBC BRCA1/2 carriers are at risk to develop bilateral disease; however, they are similarly susceptible for local recurrence, distant metastases and mortality.
authors.affiliation: Department of Nursing, The Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Dagan
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.|The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Kurolap
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel.|Institute of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Fried
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007585:Jews; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: 
  BRCA1/2
  ; bilateral breast cancer; early onset breast cancer