title: Prospective study of high-risk, BRCA1/2-mutation negative women: the 'negative study'.
abstract: BACKGROUND
  We previously reported that women from high-risk families who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation were four times more likely to develop breast cancer compared to women in the general population. Preventive measures and risk factors for breast cancer development in these high-risk women have not been evaluated to the same extent as BRCA1/2 positive women. Further, there is virtually no scientific evidence about best practices in their management and care. The proposed study will examine a role of genetic and non-genetic factors and develop the systems and parameters for the monitoring and surveillance necessary to help establish guidelines for the care of this high-risk population.
  
  
  METHODS
  To achieve our goals, we will assemble and follow a Canadian cohort of 1,000 cancer-free women with a strong family history breast cancer (defined as two or more relatives affected by breast cancer under the age of 50, or three or more relatives diagnosed with breast cancer at any age from one side of the family and with no BRCA1/2 mutation in the family). All eligible participants will be mailed a study package including invitation to participate, consent form, a research questionnaire to collect data regarding family history, reproductive and lifestyle factors, as well as screening and surgery. Usual dietary intake will be assessed by a diet history questionnaire. Biological samples including toenail clippings, urine and blood samples will be collected. These women will be followed every two years by questionnaire to update exposure information, screening practices, surgical and chemoprevention, and disease development.
  
  
  CONCLUSIONS
  Findings from this study will serve to help establish clinical guidelines for the implementation of prevention, counseling, and treatment practices for women who face an elevated risk of breast cancer due to family history, but who do not carry a BRCA1/2 mutation.
authors.affiliation: Familial Breast Cancer Unit, Women's College Research Institute, 790 Bay St, 7th Floor, Toronto, ON M5G 1 N8, Canada. joanne.kotsopoulos@wchospital.ca.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
authors.forename: Kelly
authors.initials: K
authors.lastname: Metcalfe
authors.forename: Jill
authors.initials: J
authors.lastname: Alston
authors.forename: Dina
authors.initials: D
authors.lastname: Nikitina
authors.forename: Ophira
authors.initials: O
authors.lastname: Ginsburg
authors.forename: Andrea
authors.initials: A
authors.lastname: Eisen
authors.forename: Rochelle
authors.initials: R
authors.lastname: Demsky
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akbari
authors.forename: Kevin
authors.initials: K
authors.lastname: Zbuk
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D002170:Canada / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D011446:Prospective Studies; D062486:Public Health Surveillance / Q000379:methods; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human