What are the BRCA1 and BRCA2 genes?

BRCA1 and BRCA2 are genes that produce tumour suppressor proteins. These proteins help prevent uncontrolled cell proliferation and DNA damage, which can lead to the development of cancer. Mutations or changes in these genes can disrupt the function of tumour suppressor proteins, increasing the risk of breast, ovarian and other cancers. Testing for mutations in these genes can help individuals and their doctors make informed decisions about cancer prevention and treatment options. Inherited mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased risk of breast and ovarian cancer, as well as some other types of cancer, such as pancreatic and prostate cancer. Women with an inherited BRCA1 or BRCA2 mutation have up to a 72% risk of developing breast cancer in their lifetime and up to a 44% risk of developing ovarian cancer in their lifetime. BRCA1 and BRCA2 mutations are relatively rare in the general population. Screening for BRCA1 and BRCA2 mutations may be recommended in people with a personal or family history of breast or ovarian cancer, especially if the cancers were diagnosed at a young age or several family members are affected.

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

Inherited mutations in the BRCA1 and BRCA2 genes significantly increase the risk of developing ovarian cancer. Women with an inherited BRCA1 or BRCA2 mutation have up to a 44% risk of developing ovarian cancer in their lifetime, compared to the general population's risk of about 1-2%. The exact level of risk can vary depending on several factors, including the specific mutation involved, the age at which the mutation carrier was diagnosed with breast cancer and family history of breast and ovarian cancer. Women with a BRCA1 mutation are thought to have a higher risk of ovarian cancer than women with a BRCA2 mutation. It is important to note that not all women with a BRCA1 or BRCA2 mutation will develop ovarian cancer and other factors may also contribute to the risk of developing the disease. Women with an inherited BRCA1 or BRCA2 mutation should work closely with their physicians and genetic counselors to develop an individualized risk management plan, which may include regular ovarian cancer screening and/or risk-reducing surgery.

Who should be tested for mutations in the BRCA1 and BRCA2 genes?

Genetic testing for mutations in the BRCA1 and BRCA2 genes may be recommended in people with a personal or family history of breast or ovarian cancer, especially if the cancers were diagnosed at a young age or several family members are affected. This includes:

• Women diagnosed with breast cancer before the age of 50
• Women diagnosed with ovarian cancer at any age
• People who have a family history of breast or ovarian cancer, especially if the cancer occurred in a close relative such as a mother, sister or daughter, or if several family members are affected
• People of Ashkenazi Jewish descent, as they are more likely to carry a BRCA1 or BRCA2 mutation

It is important to note that not everyone who meets these criteria will have a BRCA1 or BRCA2 mutation and not all people with a mutation will develop cancer. Genetic testing can help identify individuals who are at increased risk for cancer and may benefit from earlier or more intensive testing, risk-reduction surgery or other risk management strategies. Genetic counseling is recommended before and after genetic testing to help individuals understand their test results and make informed health decisions.

How should women with mutations in the BRCA1 and BRCA2 genes be screened for ovarian cancer?

Women with BRCA1 and BRCA2 gene mutations are at higher risk of developing ovarian cancer and screening can help detect ovarian cancer at an early, more treatable stage. The most effective screening method is regular transvaginal ultrasound and CA-125 blood tests. These tests are usually recommended every six months starting at age 30 to 35 years or five to ten years earlier than the earliest age of ovarian cancer diagnosis in the family. In addition to screening, some women with BRCA1 and BRCA2 mutations may choose to undergo risk-reduction surgery to remove their ovaries and fallopian tubes, known as prophylactic salpingectomy. This surgery can significantly reduce the risk of ovarian cancer and is usually recommended after childbearing is complete or after the age of 35. Women with BRCA1 and BRCA2 mutations should work closely with their healthcare provider to develop a personalised plan for ovarian cancer screening and prevention that takes into account their individual risk factors, preferences and overall health.

Prophylactic salpingectomy in women with BRCA1 and BRCA2 mutations in the prevention of ovarian cancer

Prophylactic salpingectomy, or the removal of the fallopian tubes and ovaries, has been shown to be particularly effective in reducing the risk of ovarian cancer in women with BRCA1 and BRCA2 mutations. In fact, studies have shown that the procedure can reduce the risk of ovarian cancer by up to 80-90%. For women with BRCA1 or BRCA2 mutations, the American College of Obstetricians and Gynecologists (ACOG) recommends that prophylactic salpingectomy be considered between the ages of 35 and 40 or when childbearing is complete. This recommendation is based on the fact that the risk of ovarian cancer increases significantly after age 35 and that the benefits of surgery generally outweigh the risks for most women. It is important to note that while prophylactic salpingectomy is highly effective in reducing the risk of ovarian cancer, it also has potential risks and side effects, such as early menopause and an increased risk of heart disease and osteoporosis. Women with BRCA1 or BRCA2 mutations should discuss individualized risk and management options with their healthcare providers and genetic counselors to make informed decisions about their health.

Is there a drug treatment to reduce the risk of ovarian cancer in women with mutations in the BRCA1 and BRCA2 genes?

Yes, there are drugs that can help reduce the risk of ovarian cancer in women with mutations in the BRCA1 and BRCA2 genes. One option is the use of oral contraceptives, which have been shown to reduce the risk of ovarian cancer by up to 50% in women with BRCA1 or BRCA2 mutations. It is thought that hormones in oral contraceptives may help prevent the development of ovarian cancer by suppressing ovulation and reducing the number of ovulation cycles. Another option is the use of PARP inhibitors, which are drugs that target specific proteins involved in DNA repair. In women with BRCA1 or BRCA2 mutations, PARP proteins may be less effective in repairing DNA damage, making cancer cells more vulnerable to the effects of PARP inhibitors. Studies have shown that PARP inhibitors may be effective in reducing the risk of ovarian cancer in women with BRCA1 or BRCA2 mutations who have not undergone prophylactic salpingectomy. However, it is important to note that these medications have potential risks and side effects, and the decision to use them should be made in consultation with your physician. Women with BRCA1 and BRCA2 mutations should work closely with their physician to devise an individualized plan for ovarian cancer prevention that takes into account their individual risk factors, preferences, and overall health.

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

Yes, there are mutations in many other genes that have been associated with an increased risk of ovarian cancer. Some of these genes include:

• RAD51C and RAD51D: Mutations in these genes have been shown to increase the risk of ovarian cancer, as well as breast cancer and other cancers.
• BRIP1: Mutations in this gene have been associated with an increased risk of ovarian cancer, as well as breast cancer and other cancers.
• PTEN: Mutations in this gene have been linked to an increased risk of ovarian cancer, as well as several other types of cancer.
• TP53: Mutations in this gene have been associated with an increased risk of several types of cancer, including ovarian cancer.
• CHEK2: Mutations in this gene have been linked to an increased risk of breast and ovarian cancer, as well as other cancers.

Testing for mutations in these genes may be recommended for women with a family history of ovarian cancer or other cancers, as well as for women with a personal history of cancer. It is important for women to have individualized discussions with their physicians and genetic counselors. Women with a personal or family history of ovarian cancer or other cancers may be candidates for genetic testing to detect mutations in these and other genes. Genetic counseling can help individuals and their families better understand their risk and make informed decisions about their health.