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Inherited breast cancer

  • Breast cancer is the most commonly diagnosed cancer in the UK, affecting around 1 in 8 women during their lifetime.
  • The majority of breast cancer is not due to an inherited condition, but it is important to recognise the less than 5% of breast cancer that occurs due to an inherited predisposition (inherited or familial breast cancer).
  • Two major genes associated with familial breast cancer are the BRCA1 and BRCA2 genes.
  • Women with an alteration in the BRCA1 or BRCA2 genes have a significantly increased risk of developing breast (and ovarian) cancer during their lifetime, and may be offered additional screening.

Clinical features

Clues that may suggest an inherited predisposition to breast cancer include:

  • several women who have had breast cancer on one side of the family;
  • breast cancer being diagnosed at a younger age than is usual;
  • an individual who has had primary breast cancer more than once or had early breast cancer and ovarian cancer; and
  • a male with breast cancer in a family where female relatives have also had breast cancer.

Diagnosis

  • Individuals may seek information, either because they have been affected with breast cancer themselves or because they have a family history of breast cancer.
  • A family history will first be taken by their breast cancer team or by their GP. If the family history is considered to be significant, then a referral should be made to the local genetics department or family history clinic. Most regional genetic centres publish guidelines on their website for referrals based on information from a family history.
  • A detailed risk assessment will then be carried out. This will estimate an individual’s lifetime risk of developing breast cancer and also the risk of developing breast cancer over the next 10 years. An assessment can also be done to calculate the chance that there is a BRCA1 or BRCA2 gene alteration in the family.
  • At this stage, recommendations about additional screening or genetic testing may be offered.

Genetic basis

  • The two main genes associated with familial breast cancer are known as BRCA1 and BRCA2. (There are other genes known to be associated with predisposition to breast cancer, but BRCA1 and BRCA2 are those most commonly involved).
  • A woman who inherits an altered BRCA1 or BRCA2 gene will not always develop cancer, but her risk of developing breast (and ovarian) cancer will be significantly increased. For women with a BRCA1 or BRCA2 alteration, the risk of developing breast cancer before the age of 80 is around 80%. The lifetime risk of developing ovarian cancer is between 20% and 60%.
  • BRCA1 and BRCA2 mutations are inherited in an autosomal dominant manner. This means that an individual has one usual copy of the gene and one altered copy. An individual with a gene alteration has a 50% (1 in 2) chance of passing on the usual gene and a 50% chance of passing on the altered gene to each of their children, male or female. As mentioned above, if a child inherits a copy of the altered gene, it is likely but not certain that breast cancer will develop.

Clinical management

There are several options available to women at an increased risk of developing breast cancer:

  • Breast screening: The National Breast Screening Programme offers all women mammograms every three years between the ages of 50 and 70. Depending on the level of risk, breast screening may be offered from an earlier age and on a more frequent basis. Sometimes other types of examinations (such as an MRI scan) may also be offered to women at high risk.
  • Risk-reducing surgery: Some women at high risk of breast cancer may be offered surgery to reduce the risk. Double mastectomy with reconstruction can reduce the risk of breast cancer by up to 90%. However, this is major surgery with potential complications and possible psychological implications.
  • Breast awareness: Most breast cancers will present as a painless breast lump. It is important that all women are aware of how to check their breasts and know which symptoms to be aware of.

Genetic testing

  • NICE guidelines state that genetic testing for BRCA1 and BRCA2 gene alterations should be available to women where there is a 20% or greater chance of carrying a gene mutation.
  • Genetic testing first needs to be carried out in an affected member of the family. If a gene alteration is identified in an affected family member, then other relatives can also be tested to see whether they carry the same gene alteration. This is known as predictive genetic testing.

 

This information is intended for educational use and was current in August 2013. For clinical management, it is recommended that local guidelines and protocols are used.