Up to 10% of breast cancer in western countries is due to genetic predisposition.
Susceptibility to breast cancer appears to be inherited as an autosomal dominant
with limited penetrance and may thus be inherited from either father or mother.
About 5% of breast cancer is due to highly penetrant dominant genes.
than five genes are thought to be involved. The most important appears to be the
BRCA1 gene located on chromosome 17q. This has recently been cloned and thought
to have mutations present at different regions. Other genes identified include
BRCA2 on 13q and the p53 gene on 17p.
- BRCA1 carriers have a lifetime
risk approaching 80% of developing breast cancer and an increased risk of ovarian
cancer (40-60%) (1)
- BRCA2 confers a lower risk of ovarian cancer (20-30%)
but is associated with an increased risk of a wider spectrum of other cancers
including prostate cancer, pancreatic cancer, and an increased risk of male breast
- in the UK general caucasian population - frequency of mutations
in BRCA1 or BRCA2 is approximately 1/400; in the Ashkenazim population the frequency
of these mutations is about 2% (1)
- management of breast cancers in BRCA1
and BRCA2 carriers is currently the same as for sporadic cases, except that bilateral
mastectomy may be offered at the time of primary surgery because of the increased
risk of development of breast cancer in the contralateral breast (about 4% per
Characteristics of familial breast cancer include:
early age of presentation
- several relatives are affected
involvement is common
- history of related cancers - colorectal, ovary,
If a first-degree relative has breast carcinoma, the
relative risk of developing breast carcinoma is 1.7 to 2.5. If a second-degree
relative is affected, the relative risk is 1.5.
DNA tests are possible
for a few suitable families.
Mutations in the CHEK2 gene may increase the
risk of breast cancer two-fold (1).
- Pulse (2005);
- Evans DGR et al. (1994). Familial breast cancer. BMJ; 308:183-7
McPherson et al. (1994). BMJ;309: 1004