BRCA 1 & 2 Genetic Test - Breast Cancer

Is genetic testing for breast cancer worth it?

BRCA 1 and 2 are breast cancer (Ca) susceptibility genes. So this genetic testing for breast and other cancers is worth it because this blood test uses DNA analysis to determine whether a person has inherited harmful changes or mutations in the genes that can increase the risk of breast Ca. Germline mutations in BRCA gene significantly increases the risk of breast and ovarian Ca in people harboring these mutations as opposed to those not having them. Cancer risk is lesser in individuals without BRCA mutation. People who inherit these mutations are at a greater risk of developing cancers as compared to general population. Additionally these genes are implicated in small proportion of male breast cancers and other malignancies like prostate Ca, pancreatic Ca and melanoma.

What percentage of breast cancer is related to BRCA1 and BRCA2?

About 5-10% of breast Ca are linked to BRCA mutations. So we see they are not very common cause for cancers. Nevertheless testing is always recommended as mutation positive genes run the family. If a cancer patient is tested positive for these mutations, timely screening of other family members is needed as chances of mutation positivity in them is about 50%. If anyone is detected as positive, it increases the chances of getting cancer in future. They can be put on regular monitoring by doing more screening tests like mammography, MRI, ultrasound imaging or blood tests (CA-125) and keep regular follow up with the clinician. This will help in timely diagnosis and management, if at all he or she is diagnosed with any cancer.

Does BRCA1 or BRCA2 cause breast cancer?

Yes. BRCA 1 and BRCA 2 are tumor suppressor genes. They provide instructions for making proteins which function as tumor suppressor. They prevent cells from growing and dividing too rapidly or in an uncontrolled fashion. When mutations occur, this function gets lost resulting in development of cancers.

What is BRCA1 and BRCA2 testing?

BRCA1 and BRCA2 testing is done by an extremely advanced molecular genetic testing called NGS (next generation sequencing) methodology. Results are reported as “detected” or “not detected”.

This test can be a part of genetic counseling when certain patterns of cancers run in the family. Indications for BRCA genetic testing are people having personal history of:

i) breast Ca diagnosed before 45 years of age

ii) breast Ca diagnosed before 50 years along with a second primary breast Ca, one or more immediate relatives like parents, siblings or children diagnosed with breast Ca before 50 years of age, two more relatives known to have breast Ca at any age or an unknown or limited availability of family medical history

iii) triple negative breast Ca (negative for estrogen receptor, progesterone receptor and HER2 Neu) diagnosed at or before 60 years

iv) having two or more types of cancers

v) ovarian, fallopian tube or primary peritoneal Ca or one or more relatives having ovarian Ca

vi) male breast Ca, one or more relatives with male breast Ca or two or more relatives having prostatic or pancreatic Ca

vii) metastatic prostate or pancreatic Ca, viii) Two or more relatives known to have BRCA 1 or 2 mutations or diagnosed with any BRCA-associated cancers 

ix) Cancer at any age if ethnic origin is Ashkenazi Jews. Both side family histories become important and needs to be considered as these mutations can be inherited from either of the parent.

What is hereditary breast-ovarian cancer syndrome (HBOS)?

HBOS is an inherited cancer-predisposition syndrome and is considered when there are multiple cases of breast and ovarian Ca on same side of the family. Variations in BRCA1 gene lead to increased risk of getting breast Ca in both sexes and ovarian Ca in females, as a part of HBOS. Women with abnormal BRCA 1 or 2 genes have 80% risk of developing breast cancer by 90 years of age. Risk of developing ovarian cancer is also increased to 55% and 25% with BRCA 1 and BRCA 2 gene mutations respectively.