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Family history predicts high breast cancer risk despite negative gene tests

23 November 2008
Appeared in BioNews 485

A study undertaken in Canada shows that women who test negatively for gene mutations associated with breast cancer may still be at high risk if there is a strong presence of the disease in their family. Author of the study Dr Steven Narod, Canada Research Chair in breast cancer at the University of Toronto said, 'it was assumed that most of the risk could be explained by [gene] mutations', referring to the mutations in the genes BRCA1 and BCRA2 which are linked to particularly aggressive hereditary breast cancer. However, Dr Narod's study indicates that BCRA gene mutations are only responsible for breast cancer in one in every five families tested.

Narod's study followed 1,492 Canadian women who did not carry the mutated genes but had a history of breast cancer in the family. After five years, these women were four times more likely to have developed breast cancer than the average woman.

'The findings suggest that additional genes, hormones, or other unknown factors, perhaps environmental, are also responsible for causing breast cancer', Narod said. 'It is clear to me that the risk is high enough that we need to discuss options such as breast MRI (Magnetic Resonance Imaging) screening and chemoprevention with tamoxifen or raloxifene. Our hope is to be able to prevent or pick up on breast cancer early enough to stop patients from dying'.

It is thought this revelation will enable clinicians to give better counselling to families with a prevailing history of breast cancer but who do not necessarily present with the associated gene mutation. Kelly Metcalfe, also of the University of Toronto said 'it has been difficult to counsel women without a mutation...For a woman with a significant family history of breast cancer, without a BRCA1-2 mutation, we can now say that she has an approximate 40 per cent risk of developing breast cancer'.

Dr Narod recommended that women without gene mutations but with three or more family members with breast cancer should undergo MRI screenings and consider taking tamoxifen, an oestrogen suppressant used to prevent breast cancer tumours. 'You can reduce the risk from 40 to 20 per cent - pretty dramatic figures'.

Beth Peshkin, a genetic counsellor at Georgetown University, Washington said that the findings were crucial for women considering having genetic testing. 'This is contrary to what I think the common perception is;' Peshkin said, 'a negative test doesn't provide reassurance'.

Some positive news came from the study to show that although carriers of the BCRA genes are also at increased risk of ovarian cancer, the women in Dr Narod's study were not.

SOURCES & REFERENCES
Breast cancer risk high from family history, without mutations: study
CBC News |  18 November 2008
Family history can trump breast cancer gene test
Associated Press |  17 November 2008
Family History Raises Breast Cancer Risk
WebMD |  17 November 2008
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