Genetics, Hereditary and Breast Cancer Risk

Breast cancer can run in families and if you have a mother or sister with breast cancer then you will have an increased chance of getting it. Sometimes it is not known why this happens and it could be because some families share the same lifestyle or that there are factors contributing ,which we do not yet know about.

Hereditary Breast Cancer and BRCA Genes:
About 5-10% of all breast cancers arise because of a faulty gene – known as a mutation or alteration– which has been inherited ,from either  parent. This increases their risk of getting breast cancer significantly. This is called hereditary breast cancer.

The most well-known genes which can affect breast cancer risk are the BRCA genes (BRCA 1 and BRCA 2). These genes  usefully repair DNA and they normally protect us from developing breast cancers.They are called tumour suppressor genes. We all have 2 copies of both of these BRCA genes – one from our mother and one from our father. If just one copy is abnormal – inherited from either parent-then there is a much higher lifetime risk of developing breast cancer. 

What is the Impact of Carrying an Abnormal BRCA Gene?

The presence of an abnormal BRCA gene means that damaged DNA may not get repaired as it should and this can lead to a cancer developing. If you carry a faulty BRCA gene you will have an overall 50-80% risk of getting breast cancer in your lifetime. There is also an increased risk of developing other cancers such as cancer of the ovary , colon , skin melanomas and pancreatic cancers. Men also have BRCA genes just like women. They can also inherit the abnormal BRCA gene from either parent and this increases their chance of male breast cancer and prostate cancer.

Who Has an Abnormal BRCA Gene?

The BRCA gene mutation occurs randomly in 1 in 400 in the UK population. However in certain communities in the world, the presence of an abnormal BRCA gene is much higher. In populations who have historically lived in isolation or geographically do so, the abnormal gene has been passed from one generation to another.  Some examples include Icelandics, French Canadians, the Orkney islanders, and Ashkenazi Jews.

Abnormal BRCA Genes in the Jewish Population

Ashkenazi Jews (AJ) are Jewish people whose ancestry is from Western, Central and Eastern Europe. Through population migrations, some with Russian, Ukrainian, Polish, Iranian, Iraqi, Middle Eastern, Indian (Kerala) and Mediterranean ancestry, may also have inherited this mutation. In this population, the abnormal BRCA gene is present in 1 in 40 people. If you have a grandmother or a grandfather with Ashkenazi Jewish ancestry then there is a 2.9% risk of  you carrying an abnormal BRCA gene. In AJ who have a family history of breast and other BRCA related cancers, their individual risk of carrying an abnormal BRCA mutation increases to 10%.

In view of the high incidence of a BRCA mutation in the Jewish community, in 2023 the NHS launched a testing programme inviting both men and women with Jewish heritage to have their BRCA genes tested. This can determine whether an  individual is carrying an abnormal BRCA gene. This was an initial pilot study but due to high demand and uptake it is going to continue. To register for this you need to be over 18 years, and have one grandparent who is/was Jewish. Registrations are at jewishbrca.org.

Are There Other Genes Which Can Affect Breast Cancer Risk?

Yes, there are other inherited genes which ,if faulty or altered,can increase an individual ‘s risk of hereditary breast cancer. These include PALB2, CHEK2,TP53 and PTEN. These genes are also inherited from either parent.Inheritence of only one abnormal copy will increase the lifetime risk of cancer. Families with these genes will often have a history of breast and other cancer in more than one generation. There are genetics clinics who  will see an individual  and their families if there is a strong family history of breast and other cancers. These clinics can test for any BRCA mutations and  other less common genes which if abnormal can cause breast cancer. You can be referred to these Familial Genetics clinics by your GP.

What Can You Do if You Have a BRCA or Other Gene Mutations.

If an abnormal gene is found in your family, you will be offered genetic counselling and discussion regarding a management plan for the future.

Some options include:

• Screening – this involves regular medical checks looking for any abnormal changes in the breast and ovary as soon as they arise. This is done with mammograms, MRI scans and blood tests often from the age of 25 years.
• Risk -reducing Surgery – some women elect to have their breast (and ovarian) tissue removed ,before they develop any abnormalities or cancer. This is not a decision that is taken lightly and involves a lot of discussion and consideration. Many will have breast reconstructions after this. This surgery will reduce the risk of getting breast cancer by over 90%.
• Preventative medication – some women chose this. These drugs such as Tamoxifen and raloxifene reduce the risk of certain breast cancers which respond to oestrogen.
• PARP inhibitors: these drugs are used in cancer  treatments of BRCA mutation carriers , but in future could be offered for risk-reduction, with no evident cancers.
• Healthy Lifestyle – practising a healthy lifestyle such as limiting alcohol, improved exercise routines, and maintaining a healthy body weight can reduce the risk of breast cancer in everyone. This should be something that all women do, but it is beneficial in risk reduction even in those who have an inherited genetic risk of breast cancer and explains why some with genetic mutations will never develop breast cancer. 20-50% will not develop breast cancer with a BRCA mutation.
  

Preimplantation Genetic Testing PGD in Those with a BRCA Mutation

Many women who have an abnormal BRCA gene are concerned that they may pass this abnormal gene onto their  future babies. Preimplantation genetics involves a form of In Vitro Fertilisation (IVF) where the fertilised  embryos are checked in the laboratory for a BRCA mutation. Only embryos with normal BRCA genes are then re-implanted and transferred to the mother’s womb where hopefully a healthy baby will develop. You can be referred for this by your GP or familial genetics clinic to a special fertility unit.