BRCA1 & BRCA2 Plus

Breast cancer is the most common cancer in the UK. Unfortunately, 1 in 7 women will develop breast cancer during their lifetime; with 80% being diagnosed after the age of 50. 1 in 868 men will also be diagnosed with breast cancer. 

Most breast cancer occurs by chance, however approximately 5-10% is hereditary and in some families, ovarian cancer can be genetically related to breast cancer. In families where breast cancer is hereditary it may be possible to find the genetic change (pathogenic variant) which is responsible for the cancer. This allows for appropriate cancer screening and risk-reducing options.

How do I know if I am at risk?

Individuals with hereditary breast cancer generally show one or more of the following clues:

• Triple negative breast cancer
• Breast cancer diagnosed before the age of 45
• Bilateral breast cancer (cancer in both breasts)
• Several relatives with breast cancer
• Relatives with Ovarian, prostate, pancreatic cancer or male breast cancer
• Jewish ancestry

The following genes shown below have been shown to be associated with breast cancer and are tested as part of BRCA Plus.

• ATM,
• BARD1
• BRCA1
• BRCA2
• CHEK2
• PALB2
• PTEN
• STK11
• TP53
• RAD51C
• RAD51D  

Genes come in pairs; we get one copy from our mother and one copy from our father. At present most cancer syndromes are inherited in a dominant pattern. This means that if someone has a pathogenic variant in one copy of a gene then there is a 50% chance that they will pass this onto their children. The risk of breast cancer can be inherited from either side of the family. The diagram below illustrates this:

How can genetic testing help? 

Genetic testing can help determine the risk of cancer within a family and guide appropriate cancer screening. Depending on the specific genetic risk, different screening tests can be arranged, and risk-reducing strategies can be considered.

No, if you wish you can choose to be tested for some or all the nine genes in the panel. The number of genes tested will not affect the testing time or pricing.

There are three possible results:

1. A pathogenic variant is found in one of the genes which is known to increase the risk of breast cancer. If you have been diagnosed with cancer, this may change your treatment. Increased screening and/or risk-reducing techniques will be recommended.
2. A variant of unknown significance is found (VUS), but whether this is the definite cause of cancer is unknown. Screening will be recommended based on the family history.
3. No pathogenic variants are found. It is possible that there may be an undetectable variant or a variant in a different gene. Cancer screening may still be beneficial.

If you have a pathogenic variant this will explain why you and/or your relatives have developed breast cancer and means that you have an increased risk of breast cancer and possibly other cancers. Your exact risk(s) will depend on which gene pathogenic variant has been found. Extra screening and/or risk-reducing strategies will be discussed. It will also be possible to offer predictive testing to other people in your family to see if they also have the pathogenic variant.

When someone has an increased risk of breast cancer it is usual for them to have screening mammography and often breast MRI scans. The frequency and timing of screening will depend on which genetic pathogenic variant is found.

Screening for other cancers may also be needed and will be discussed if necessary.

Unfortunately no screening is 100% effective and in some situations, people may wish to consider risk-reducing surgery. In particular, risk-reducing mastectomy to remove healthy breast tissue may be considered by some women. This is very much an individual decision and obviously needs careful consideration. If a woman wishes to consider this option, her breast surgeon can provide further information.

Additionally, women with a BRCA mutation may consider bilateral salphingo-ophorectomy (removal of the ovaries and tubes).

It is important for all women to be ‘breast aware’ which means becoming familiar with how your breasts look and feel. Many women have lumpy breasts, which naturally change depending upon the time in your menstrual cycle and therefore it is best to check yourself at the same time each month (mid-cycle). If you notice a change in your breasts it is important to seek medical advice.

Signs of breast cancer are:

lumps, thickening or bumpy areas
changes in appearance, like puckered or dimpled skin
discomfort or pain
bloodstained nipple discharge
a rash or red area on the nipple or areola that won’t heal,
a change in your nipple position (pointing differently or pulled in).

Most of the time people with these signs will not have cancer but it is always important to get them checked out.

Some hormonal factors have been suggested as breast cancer risk factors. In particular, it is known that early menarche (first period) and late menopause increase the risk of breast cancer. Breast-feeding lowers the risk of breast cancer, as does early childbirth (before the age of 30).

It is known that the pill lowers the risk of ovarian cancer when taken for five or more years. However, there may be a slightly increased chance of developing breast cancer for women who take the pill for prolonged periods; this risk decreases once women stop taking the pill.

Hormone replacement therapy (HRT) increases the risk of breast cancer when used after a natural menopause however it may be helpful for women who have an early surgically induced menopause.