A recent announcement by Angelina Jolie has brought attention to BRCA gene mutation again and the increased risk of developing breast and ovarian cancer. She announced her “double mastectomy” to minimize the risk of developing breast cancer in the future. In the near future, she will also announce removal of her ovaries to minimize the development of ovarian cancer.
Patients with BRCA mutation are at a greater risk for developing breast, ovarian, colon, pancreatic and prostate cancer. There are two main types of gene issues and include BRCA 1 and 2 type deletions. The risk of breast cancer can be up to 80% and ovarian cancer between 40-60% in BRCA 1 mutation carriers and slightly lower in BRCA 2 mutation carriers. Men can be carriers of BRCA gene deletion as well, but the risk of development of cancer in men is much lower than women for the same gene mutation.
BRCA is a tumor suppressor gene and when parts of this gene are deleted (missing or replaced), tumor cells can form and the genes can be activated to stimulate cancer development. The challenge with BRCA screening is cost and also the low probability of having the gene deletion which is estimated to be 1 in 500-1000 in the general population. Therefore, universal screening of women is not recommended, but when certain risk conditions are met, testing should be offered. These risk factors include but are not limited to having a family history of breast and/or ovarian cancer in more than one family member under age 50, men with breast cancer, having breast cancer in both breasts at the same time or presence of multiple family members with ovarian and breast cancer. It’s also important to know that in women with breast or ovarian cancer, the risk of having a genetic component is actually not more than 10%. In other words, 90% of ovarian and breast cancers are in fact not due to BRCA mutations.
Genetic testing of embryos for BRCA:
A common question is whether embryos should be tested for BRCA mutation in women undergoing In Vitro Fertilization (IVF) treatment. Whereas testing would identify those embryos with the gene disorder, practically the chances of finding embryos with the BRCA mutation are very low and therefore routine screening for BRCA gene mutation would not be recommended. This is in contract to women who are carriers of BRCA mutation who also have infertility. In such cases, embryos are already being created for the purpose of IVF treatment and testing should be strongly considered. Testing can be done through embryonic stem cells obtained from blastomere (Day 3 biopsy) or trophectoderm biopsy (Day 5 biopsy).
It would be useful to test embryos for the gene disorder and only transfer embryos that are free of BRCA mutation. This would not only improve the chances of pregnancy within that transfer cycle, but also minimize the risk of the child carrying the gene, developing breast or ovarian cancer in the future.
Women who are considering egg freezing to preserve their reproductive potential who are also carriers of BRCA mutation should consider genetic testing of the eggs at the time of egg freezing. This can be done through polar body biopsy and screening the polar body for BRCA 1 and 2 mutations. Whereas this is not a part of routine practice with egg freezing, in women with BRCA mutation, it should be discussed as an additional option.
Patients diagnosed of breast cancer who desire future fertility should consider egg freezing regardless of BRCA mutation status. Egg freezing should ideally be done prior to starting chemotherapy, surgery or radiation therapy. Women who are in the reproductive years diagnosed with breast cancer should consult with a fertility specialist immediately and prior to initiating treatment, and regardless of the presence of BRCA mutation. The window of opportunity for preserving fertility prior to starting treatment should not be missed and all patients should be counseled appropriately.