Hereditary breast and ovarian cancer syndrome

Hereditary breast and ovarian cancer (HBOC) syndrome is caused by a mutation to either BRCA1 or BRCA2 genes. These patients have an increased risk of breast cancer, ovarian cancer, pancreatic cancer and prostate cancer. However, these gene mutations are not the only cause of hereditary breast cancer or hereditary ovarian cancer.

Terminology

As per scientific convention, the short names of genes are italicized i.e. BRCA1, but not their long names, i.e. breast cancer 1, and not their protein products which remain in plain font i.e. "BRCA1 protein" or "breast cancer 1 protein".

Epidemiology

The estimated prevalence of BRCA1/BRCA2 carriage is 1 in 550 (range 1 in 300-800) .

Pathology

BRCA1 and BRCA2 are tumor suppressor genes that encode proteins involved in DNA repair. More than a thousand mutations to each gene have been detected, and cancer develops after inheritance of a mutated BRCA1/BRCA2 gene from one parent, followed by mutation to the second normal BRCA1/BRCA2 gene from the other parent ("two-hit hypothesis") .

The risk of specific cancer type above the general population risk varies depending on the mutation :

• BRCA1 mutation
  • breast cancer: ~65%
    • second primary breast cancer: ~30% at 5 years
  • male breast cancer: 1-2%
  • ovarian cancer: ~32.5%
  • prostate cancer: <30%
  • pancreatic cancer: ~2%
  • colorectal cancer: 5x increased risk if <50 years
• BRCA2 mutation
  • breast cancer: ~55%
    • second primary breast cancer: ~10% at 5 years
  • male breast cancer: ~7.5%
  • ovarian cancer: ~15%
  • prostate cancer: <40%
  • pancreatic cancer: ~5%
  • colorectal cancer: no increased risk