How are mutations in the BRCA1 and BRCA2 genes inherited?

BRCA1 and BRCA2 mutations can be inherited by the descendants from both the mother and the father. The chance of children inheriting these mutations is 50%.   

How do mutations in the BRCA1 and BRCA2 genes increase the chance of developing ovarian cancer?

The chance of developing ovarian cancer in a woman’s lifetime is estimated at 1.3%. In contrast, in BRCA1 mutation carriers, the corresponding chance is 44%. For women carrying a BRCA2 mutation, the risk of developing ovarian cancer is close to 17%.

Which women should be genetically tested for mutations in the BRCA1 and BRCA2 genes?

Genetic counseling and related testing are recommended for women who:

• Have been diagnosed with ovarian cancer, regardless of age.
• Have been diagnosed with breast cancer at the age of 50 or earlier. In case of “triple-negative” breast cancer, the test should be done in women who developed it at the age of 60 or earlier.
• Have many family members with breast or ovarian cancer, especially if diagnosed under the age of 50.
• Have individual history or close relative’s history with more than one malignancy, such as bilateral breast cancer or breast and ovarian cancer.
• Have a family history of cancer running over many generations. It is important to get detailed information about both the mother and father side.
• Have individual or family history of malignancies other than breast and ovarian cancer (e.g., pancreatic, prostate or breast cancer in a man).

What are the screening tests that women with BRCA1 and BRCA2 gene mutations should undergo to prevent ovarian cancer?

Many foreign scientific companies recommend that women with mutations in BRCA1 and BRCA2 genes should undergo a clinical examination, measurement of the CA-125 tumor marker in blood, and ultrasound of their genitals every 6 months. The above tests should start at the age of 30.  

Are there medicines that can reduce the risk of ovarian cancer in women with BRCA1 and BRCA2 gene mutations?

Contraceptives reduce the risk of ovarian cancer, both in the general population and in women with mutations in BRCA1 and BRCA2 genes. However, their long-term use may increase the risk of breast cancer. It is advised to consult an expert before you start taking contraceptives.   

How effective is prophylactic ovary removal in women with BRCA1 and BRCA2 mutations to prevent ovarian cancer?

The most effective way to prevent ovarian cancer in women with mutations in BRCA 1 and BRCA2 genes is surgical removal of the ovaries. The simultaneous removal of the fallopian tubes is very important, as newer data highlight the fact that the vast majority of ovarian cancer, especially in the aforementioned women, start from the fallopian tubes. This precursor lesion is called serous tubular intraepithelial carcinoma (STIC) and its diagnosis requires pathological processing of the surgical preparations in accordance with the SEE-FIM protocol, as recently described by Harvard University. Nowadays, surgery is performed laparoscopically and results in a reduction of the probability of the disease by 80-90%. The additional benefits include the possible reduction of the risk of breast cancer by 50-60%. To maximize their protection, carriers of BRCA1 and BRCA2 mutations should:

• Undergo the operation once they complete their family planning, or at the age of 35-40 years, at the latest,
• Have a follow-up after the surgery due to the risk of development of peritoneal cancer in the future (2-4%). Although the ideal follow-up protocol has not been clarified yet, clinical examination and measurement of CA-125 levels in the blood at least once a year are recommended.

Are there mutations in other genes that increase the risk of ovarian cancer?

The risk of developing ovarian cancer increases in other gene mutations, as well, such as in the BRIP1, RAD51C, RAD51D, STK11 genes and in the Lynch syndrome. If you are a carrier of such a pathogenic mutation, seek for specialized medical advice about the ways to prevent the disease.