BRCA testing: Genetic testing for breast cancer
BRCA testing for breast cancer is used to identify mutations in the BRCA1 and BRCA2 genes, to assess risk of cancer and sensitivity to therapies. BRCA1 and BRCA2 are tumor suppressor genes that code for proteins which play a role in ensuring the stability of cellular DNA. These proteins are associated with repairing any DNA damage that may occur. However, a mutation in these genes result in lowered production or improper function of this protein, associated with an increased likelihood of developing genetic alterations that could lead to cancer.
Though only 5 to 10% of breast cancer incidences are due to inherited mutations, breast cancer risk is substantial among women with germline BRCA mutations. BRCA testing will help in the risk assessment of breast and ovarian cancer, which is required for genetic counselling. Women who are found to be at high risk for such mutations can be counselled for increased surveillance and/ or prophylactic surgeries.
There are numerous studies which have been carried out to identify the penetrance of these genes among different populations. The estimated cumulative risks among women of European ancestry for breast cancer vary between 45% and 85%, while that for ovarian cancer vary between 10% and 65% by age 70 years. A meta-analysis showed that BRCA1 mutation carriers had a 59% risk for breast cancer and 40% risk for ovarian cancer, while BRCA2 mutation carriers had 49% increased risk for breast cancer and 18% increased risk for ovarian cancer.
Are all BRCA mutations harmful?
There are certain inherited mutations in BRCA1 and BRCA2 genes that are known to increase the risk of female breast and ovarian cancers, as well as certain other cancers. People who carry these mutations are not only at a higher risk of developing breast cancer at a younger age but may also be at an increased risk of several other types of cancer. People who have inherited mutations in BRCA1 and BRCA2 tend to develop breast and ovarian cancers at younger ages than people who do not have these mutations.
Breast Cancer Information Core have collected information on more than 1800 mutations in the BRCA1 gene and 2000 mutations in the BRCA2 gene. This includes missense mutations, intronic changes,insertions and deletions. The different mutations are known to confer differing risk for breast or ovarian cancer. The mutations are therefore classified as
- strong and potential clinical significance
- unknown clinical significance
- benign or likely benign variants.
The BRCA1 or BRCA2 mutations may be inherited either form the mother or from the father. BRCA testing may be used to identify the predisposition for breast cancer, but only about 5–10% of breast cancer cases are hereditary. Among women who carry germline BRCA mutations, the risk for breast cancer is substantial.
BRCA testing and Therapy:
Apart from the increased risk of secondary cancers among individuals who carry certain mutations in the BRCA genes, there are certain other features of BRCA induced breast cancers.
What are the types of cancers associated with BRCA mutations?
The following table is from the NHS foundation trust
|Breast cancer in unaffected women (up to age 80)||60–90%||45–85%|
|Women with breast cancer (unilateral) Lifetime risk of a new cancer in the other breast||50%||50%|
|Lifetime risk of a new cancer in the other breast||5 year risk of new breast cancer ~10%||5 year risk of developing a new breast cancer ~ 5–10%|
|Ovarian cancer lifetime risk||Risk increases from age 40||Risk increases from mid-late 40s|
|Male breast cancer, lifetime risk||0.1–1%||5–10%|
|Prostate cancer lifetime risk||~10% Similar to population risk||20–25%|
Type of Breast Cancer: BRCA1 mutation-associated breast cancers are found to be associated with a higher risk of triple negative when compared with sporadic cases of breast cancer while those associated with BRCA2 mutations are associated with an increased likelihood of estrogen receptor positive breast cancers.
Prognosis determination: BRCA testing cannot be used to solely determine prognosis as age, type of therapy and health status of the individual also play an important role. However, the test can be used as a complimentary test, along with other determinants, to identify prognosis.
Management after BRCA testing
BRCA testing can be used to determine predisposition risk for breast cancer, prognosis and can be used to identify response to therapy.
Not everyone who carries a BRCA mutation is at an increased risk of breast cancer. If an individual carries BRCA mutations, then increased screening should be carried out.
According to the NIH (National Institute of Health), the following screening schedule is recommended for BRCA carrier:
|Age||Annual mammography||Annual MRI|
Being breast aware- Breast self examination
To detect breast cancer early, it is important for women to be breast aware. This involves noticing changes that may occur in the breast. A breast self examination should be carried out at home by feeling the breast with a palm of the hand. This examination should be carried out every month, about 5 to 10 days after menstrual period. Any changes detected should be brought to the notice of a medical practitioner.
Women who carry BRCA mutations have the option of deciding between increased screening or they could opt for risk reducing mastectomy. A risk reducing mastectomy involves removing as much of breast tissue as possible, which would reduce the risk of breast cancer by 90 to 95%.
BRCA testing can also be used to identify risk of breast cancer on use of oral contraceptives and breast size. Identifying the risk for breast cancer using BRCA testing will help in better managing lifestyle and diet to lower risk of developing the condition