Issue 

The Hereditary Breast Cancer Helpline is running a Familial Breast Cancer Week beginning on 19 June 2000. There is likely to be media attention, and an increase in the number of women seeking GP appointments with a view to referral for genetic testing.

You may already have received correspondence from a Scottish company called Rosgen. Rosgen have been granted a licence in the UK to use breast cancer disposition gene testing (BRCA-testing) technology from a US biotechnology company, Myriad Genetics Inc. Rosgen are launching their service to coincide with Familial Breast Cancer Week.

Advice 

This interim advice is not new clinical guidance, but is intended to draw your attention to existing clinical guidance from a reputable national source.

Clearly it is a matter for the judgement of the GP in each case, but generally referral for specialist genetic counselling is normally only appropriate for women at a high familial risk of breast cancer. Genetic testing may be appropriate for some of these women. It is usually necessary to define the BRCA gene mutation present in a family member affected by the disease before a predictive test can be made available to an unaffected close family member.

Women considered to have a moderate familial risk of breast cancer should not be referred for genetic testing at this time, although referral for counselling and management within clinical trials may be considered.

Women considered to have a low familial risk of breast cancer should be reassured that their risk of developing the disease is not significantly elevated. They should be advised on breast awareness, and made aware of the national breast screening programiiie if of an appropriate age.

The British Association of Surgical Oncology (BASO) has developed guidelines which suggest categories of risk for breast cancer for women according to their familial background. These are attached for information.

Background and detail 

The vast majority of cases of breast cancer arise sporadically, with no clear familial genetic susceptibility. Around 15% of women with breast cancer will have a family history of the disease. This clustering of breast cancer in a family may be due to shared environmental factors, to chance (as the disease is common), or to shared genetic factors. Known inherited gene mutations are implicated in only about 5% of all cases of breast cancer; included in these are the BRCA 1 and BRCA2 genes for breast and ovarian cancer susceptibility, associated with 2% of all cases of breast cancer. For this reason, genetic testing is not appropriate for most women with breast cancer or their families.

BRCA gene mutations are inherited in a dominant fashion (a person with one affected parent has a 50% chance of inheriting the gene). Carrying the gene mutation gives a very high lifetime risk of developing disease - it has been estimated that carriers of BRCA1 gene mutations have a risk as high as 50% of developing breast cancer by the age of 50, rising to as high as 85% by age 70.

Although all women with a family history of breast cancer are themselves at risk of developing the disease, the extent of the risk varies according to the nature of the family history. By taking an accurate family history it is possible to stratify women into those at high, medium and low risk of developing breast cancer. There is broad consensus on the criteria determining the level of risk and the recommended management, summarised in the table.

Further information

Further information is available from your local Regional Genetics Centre.

Genetic risk for women with a family history of breast cancer

Risk category Criteria determining level of risk Recommended management 
High risk (more than four times the average age related risk)
  •  Four or more relatives affected at any age by breast or ovarian cancer 
  • Three relatives affected with breast or ovarian cancer, with an average age of diagnosis of the breast cancer of less than 60 years
  • Two relatives affected by breast cancer, with an average age at diagnosis of less than 40 years
  • One relative with both breast and ovarian cancer at any age
  Referral for specialist genetic counselling at a regional genetic centre. Genetic testing may be appropriate for some of these patients.
Moderate risk (at least three times the average age related risk)
  •  One first-degree relative with breast cancer diagnosed under the age of 40 years
  • Two first- or second-degree relatives with breast cancer diagnosed under age 60, or ovarian cancer at any age 
  • Three first- or second- degree relatives with breast or ovarian cancer diagnosed at any age
  • One first-degree relative with bilateral breast cancer under age 60 
  • One first-degree male relative with breast cancer at any age
  • Current sparsity of evidence to support intervention - referral for management within clinical studies can be considered. 
  • Genetic testing is not appropriate for these patients.
Low risk  Women not falling into the above categories
  • Reassurance that the individual's risk is not significantly elevated, with discussion of the difference between familial and non-familial cancer. 
  • Advice on breast awareness (as risk of non-familial breast cancer remains). 
  • Encourage participation in the National Breast Screening Programme at age 50.

Source: British Association of Surgical Oncology Guidelines. European Journal of Surgical Oncology 1998;24:464-76.