Geni BRCA

What is the BRCA gene?

We all have 46 chromosomes in our cells. Chromosomes are made from DNA (deoxyribonucleic acid). Genes are short sections of DNA and each chromosome contains many genes. Genes contain the information our bodies need to make proteins, which play an important role in the processes that keeping our body working normally. Sometimes a gene may change (this is called a mutation) and either cause or increase the risk of a disease. See also the separate leaflet on Genetic Testing per ulteriori informazioni.

BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are two genes that everyone has. The BRCA1 and BRCA2 genes normally protect against breast and ovarian cancer. A mutation in one of these genes means that this protection is lost and a BRCA gene mutation may allow a cancer to develop. Over 2,000 different BRCA1 or BRCA2 gene mutations have so far been identified.

Other gene mutations that increase the risk of breast cancer include:

• TP53 mutation: most women with this mutation develop breast cancer by 50 years of age. TP53 is also associated with other cancers, including leukaemias and brain tumours.

• PTEN gene increases the risk of breast, thyroid, and womb (uterine) cancers.

• ATM, CHEK2, BRIP1, and PALB2 genes are also associated with an increased risk of breast cancer.

A woman’s lifetime risk of developing breast or ovarian cancer is greatly increased if she inherits a harmful variant in BRCA1 or BRCA2, but how much the risk increases will depend on the specific gene mutation.

The risk of developing cancer is highest for cancro al seno in women. But it is also higher than average for:

• Cancro ovarico.

• Cancro al pancreas.

• A number of other much rarer cancers.

Men with a BRCA1 or BRCA2 mutation have an increased risk of cancro alla prostata, and also have an increased risk of male breast cancer and pancreatic cancer.

Cancro al seno

About 13 in 100 women will develop breast cancer sometime during their lives. Some people have a higher risk of developing breast cancer because close members of their family (eg, mother, sister or daughter) have had cancer of the breast or ovary. This is called familial breast cancer (sometimes also called hereditary breast cancer). This risk is higher if a relative developed breast cancer under the age of 50 years. But most women who have a close relative with breast cancer will not develop breast cancer themselves.

The risk of breast cancer is particularly increased if you have a BRCA1 or BRCA2 gene mutation. The estimated lifetime risk of breast cancer in people with a BRCA1 or BRCA2 mutation varies, but in general:

• Women with a BRCA1 mutation have an estimated lifetime risk of breast cancer of 65-85 in 100. The estimated lifetime risk of ovarian cancer is 40-63 in 100.

• Women with a BRCA2 mutation have an estimated lifetime risk of breast cancer of 40-85 in 100. The estimated lifetime risk of ovarian cancer is 10-27 in 100.

If you already have cancer in one breast, BRCA1 or BRCA2 gene mutations are also associated with an increased risk of also developing cancer in the opposite breast. The risk of breast cancer in the opposite breast increases with time, reaching 2-3 in 10 after 10 years, and between 4-5 in 10 after 20 years, depending on the gene involved.

See also the leaflet Breast Cancer Facts and Risk Factors.

Cancro ovarico

About 1 in 100 women will develop ovarian cancer sometime during their lives. However, about 40 in 100 women who inherit a harmful BRCA1 variant and 10-20 in 100 women who inherit a harmful BRCA2 variant will develop ovarian cancer by 70-80 years of age.

Other cancers

Harmful BRCA1 and BRCA2 gene mutations increase the risk of several other cancers. In women, these include Fallopian tube cancer and peritoneal cancer.

The chance of carrying an inherited mutation in a BRCA1 or BRCA2 gene varies between different populations. For example, about 1 in 400 people carry an inherited mutation in the general population. However, women with Jewish ancestry are about 5-10 times more likely than non-Jewish women to carry BRCA1 or BRCA2 mutations.

Only about 2 in 100 breast cancers are related to a change in the BRCA1 or BRCA2 genes. However, more than 90 in 100 of inherited breast and ovarian cancers are associated with BRCA1 and BRCA2 gene mutations.

A BRCA1 or BRCA2 gene mutation can be found by a blood test. You may be offered this test if you have:

• Breast cancer at an unusually young age

• Certain types of breast cancer, such as triple negative breast cancer, at a young age. Triple negative breast cancer is a breast cancer with cells that don't have receptors for either of the hormones oestrogen and progesterone, or for a protein called HER2.

• Certain types of ovarian cancer, such as high-grade serous ovarian cancer.

• A strong family history of cancer that suggests a BRCA1 or BRCA2 gene mutation.

• A relative who is known to have a BRCA1 or BRCA2 mutation.

If genetic testing shows you have a BRCA1 or BRCA2 mutation, this does not mean you will definitely get cancer. Your risk of cancer will depend on individual factors, such as whether you are male or female, your age, the exact gene mutation, and your family history.

If you have a strong family history of breast or ovarian cancer in your family, but genetic testing finds that you do not have a BRCA1 or BRCA2 mutation, you may still have a higher risk of cancer because of the pattern of cancer in your family. Your genetics specialist will provide advice and genetic counselling, and will explain if you can have genetic testing for other types of mutation. You and your family may still be offered extra screening or treatment to reduce your risk of cancer.

If you are found to have a BRCA mutation, you will be offered screening tests to find cancer at an early stage, so that if a cancer or pre-cancerous changes do develop, they can be treated effectively with the best chance of a good outcome.

Screening del seno

Women with BRCA1 or BRCA2 mutations are offered tests to look for early signs of breast cancer. The tests offered depend on your age. The tests used include risonanza magnetica (MRI) e mammography. Ecografia may be used if MRI is not suitable or if the results of a mammografia or MRI are difficult to interpret.

Screening for other cancers

People with a BRCA1 or BRCA2 mutation are not usually offered screening for other cancers because:

• The risk of other cancer types linked to BRCA1 or BRCA2 mutations is much lower than for breast cancer in women.

• Regular screening tests cannot prevent these cancers.

• Current screening tests for these cancers are unable to detect cancer early enough to make any difference to the treatment and outcome

Prostate test
Men with a BRCA1 or BRCA2 mutation may be offered a blood test called the PSA test. This test can help to diagnose early prostate cancer and is widely available, whether or not a man has a BRCA1 or BRCA2 mutation.

Women with a BRCA1 or BRCA2 mutation may decide to have treatments to reduce their risk of breast and ovarian cancer. This may involve:

• Lifestyle changes - eg, not smoking, breastfeeding (is protective), not being overweight and regular physical activity.

• Drug treatment for a number of years (called risk reducing drugs) -eg, tamoxifen for five years for premenopausal women at high risk of breast cancer (raloxifene is an alternative for some women). A different medicine called anastrozole is used for five years for postmenopausal women.

• Surgery to remove the breasts (called risk-reducing breast surgery).

• Surgery to remove both ovaries (called risk-reducing oophorectomy) or both ovaries and Fallopian tubes (called risk-reducing bilateral salpingo-oophorectomy).

Your genetics specialist will be able to give you a great deal of information so that you are able to decide what you feel is best for you. It can also be helpful to talk to other people in the same situation, as well as talking with your family and close friends.