BRCA1

• See also BRCA
• Autosomal dominant
  • Mutation in the Breast Cancer Type 1 gene on 17q21
  • Penetrance 80-100%
• Cancer susceptibility gene
  • Regulates gene expression, probably tumour suppressing
  • Mutations generally inactivates the tumour suppressor gene
  • Not all mutations are pathogenic
• 1:800 of population are carriers of mutation
  • Up to 1% in Ashkenazi Jew population
• Risk
  • Cumulative risk of breast cancer
    • 20% at 40
    • 50% at 50
    • 70% at 70
    • 60% risk of Contralateral Ca (higher than non-BRCA Ca)
  • Cumulative risk of ovarian cancer
    • 40-60% at 70
  • Cumulative risk of other cancers
    • Colorectal Ca 6% by age 70
    • Prostate Ca 15-20% by age 70
    • Pancreatic 1-3%
• Accounts for 45% hereditary early onset breast cancer
  • 4-5% of all breast cancers
• Median age of onset 45, frequently bilateral, worse histoprognostic factors
  • More likely to be ER/PR –ve
  • 70% chance of triple negative high grade cancers
  • BUT - No difference in recurrence or death rate c.f. non-BRCA tumours