BRCA in breast cancer

Family susceptibility to breast cancer accounts for approximately 25 % of all breast cancer cases. However, in familial cancer, mutations in the BRCA 1/2, CHEK 2, TP53 and PTEN genes account for 5 -10 % of breast and ovarian cancer.

In unselected cases, BRCA 1 and BRCA 2 accounts for only 3 - 5 % of breast and ovarian cancer but higher prevalence is noted in those with a family history which are going to discuss later.

Women with BRCA 1 carries a life time risk of 80 % of developing breast cancer and 60 % of ovarian cancer, and with BRCA 2 have a life time risk of 80 % for breast cancer and 20 % for ovarian cancer.

Genetic testing criteria may differ between countries but widely accepted criteria for referral includes:

• three or more cases of breast cancer and / or ovarian cancer cases, at least one being diagnosed less than 50 years

• two breast cancer cases aged less than 40 years old

• male breast cancer

• bilateral breast cancer

Management:

Surveillance - self examinations and clinical examination twice a year together with yearly mammogram / MRI starting from age 25 - 30 years.

Chemoprevention - adjuvant tamoxifen reduces the risk of contralateral breast cancer in affected BRCA mutation carriers, while the benefit of tamoxifen for primary prevention has not been demonstrated.

Prophylactic bilateral mastectomy - most women find this strategy unacceptable for primary prevention. Contralateral prophylactic mastectomy is an option to consider in those carrier with early breast cancer.

Prophylactic bilateral salpingo-oophorectomy - it is associated with a risk reduction of breast cancer in premenopausal BRCA mutation carriers and risk reduction of ovarian cancer. It is recommended after age 35 and when child bearing decisons are complete.