Everyone has BRCA1 and BRCA2 genes which are responsible repairing DNA. Individuals having BRCA1/2 mutation are attributed to have a higher risk for triple negative breast cancer (TNBC). Some people inherit (germline) mutation from their parents which increases their risk of breast cancer due to deficient DNA repair mechanism. A person who has a BRCA1/2 mutation is sometimes called a BRCA1/2 carriers. They are at high risk of cancer and can pass the inherited mutation onto their offspring.
Carriers of BRCA1/2 mutation were also significantly more likely to have triple negative breast cancer (TNBC). Such cancers tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. The incidence of BRCA2 mutations range from 1%-17% in studies of TNBC cases unselected for age of family history. TNBC comprises about 20% of all Indian breast cancer, as many as one in three women with breast cancer could have triple-negative disease.
Positive family history with first-degree relative(s) affected with breast and/or ovarian cancer significantly increases the likelihood of detecting a mutation which result in TNBC (59%), as observed in a case-study below:
At the age of 73 Jaya* mother of two daughters and a son, was screened with 1.5 cm lump in her right breast. Further diagnosis revealed this lump to be TNBC. Which mean that the growth of her cancer is not fuelled by the hormones oestrogen and progesterone, or by the HER2 protein. Thus Jaya will not respond to hormonal therapy or medicines that target HER2 protein receptors.
It was upsetting and scary for Jaya to find out that she has been diagnosed with a type of breast cancer that is often more aggressive than other types and isn’t a good candidate for treatments. Still, other therapies which are used to successfully treat TNBC could be opted.
PARP inhibitors, have been US FDA approved to treat advanced-stage HER2-negative breast cancer in people with a BRCA1 or BRCA2 mutation. The poly ADP-ribose polymerase (PARP) enzyme fixes DNA damage in both healthy and cancer cells.
Research has shown that medicines that interfere or inhibit the PARP enzyme make it even harder for cancer cells with a BRCA1 or BRCA2 mutation to fix DNA damage. This makes it harder for the cancer cells to survive. To establish eligibility for PARP inhibitor therapy, Ad hoc genetic testing for BRCA1 or BRCA2 mutation was advised for Jaya.
Pre-test genetic counselling revealed that her brother had also been diagnosed with oesophageal cancer (cancer of food-pipe). Genetic test report of Jaya were positive for germline BRCA2 mutation, which means she is eligible for PARP inhibitors as a treatment option. Also pathogenic germline mutations in BRCA1 and BRCA2 are known to cause familial/hereditary breast and ovarian cancer syndrome (HBOC) and an increased risk towards other type of cancers.
BRCA1/2 mutations can be passed to you from either parent and can affect the risk of cancers in both women and men. Thus, Jaya’s both the daughters Rajshri*, Shilpi* and her son Yogesh* were also genetically tested for BRCA1 or BRCA2 mutation in order to determine their risk of developing cancer in the light of their mother’s positive genetic test report.
Shilpi (42 years) was positive with the same BRCA2 mutation as she inherited it from her mother. The risk of developing breast cancer in Shilpi’s lifetime is between about 69% and 72% — about 6 times greater than that her elder sister Rajshri (46 years) who was reported negative for BRCA1 or BRCA2 mutation as she did not inherited it from her mother (average lifetime risk of breast cancer 12% for non-carriers).
Their brother Yogesh was also reported positive for same BRCA2 mutation as his mother and sister. He has 7% lifetime risk of developing breast cancer and also at increased risk of developing prostate cancer.
BRCA pathogenic/Likely Pathogenic variant-positive management by NCCN can be exercised for such carriers to prevent, diagnose and treat cancer.
*- name changed to protect patient privacy
By: Fatma Islahi