Women with a high inherited risk of breast or ovarian cancer will now have access to much improved information about their chances of developing the diseases, following a report led by Cancer Research UK scientists.
The study published in the May 2003 edition of the American Journal of Human Genetics1, has reassessed the cancer risk to women with a damaged BRCA1 or BRCA2 gene but no strong family history of breast or ovarian cancer.
The new information will ensure that these women, who may contemplate surgery to remove healthy breasts or ovaries as a way of preventing cancer, are given accurate information on which to base their decision.
By age 70 a woman has a seven per cent chance of developing breast cancer and around a one per cent chance of ovarian cancer. But for women with a damaged BRCA1 or BRCA2 gene the risk of these diseases is much higher.
Previous studies had calculated the risks for women with a faulty BRCA1 and a strong family history of the disease as 87 per cent for breast cancer and 44 per cent for ovarian cancer by age 70. For women with a damaged BRCA2 the risks were estimated to be 84 per cent for breast cancer and 27 per cent for ovarian cancer by age 70.
But these risk estimates, used to counsel women, are based on cases with a strong family history of the disease where the powerful effect of the gene, along with the influence of other genes and lifestyle factors may act to increase their risk.
In this report an international team of researchers, led by Cancer Research UK’s Dr Paul Pharoah, combined data from 22 studies, with information on 500 women with a faulty version of BRCA1 or BRCA2 to reach a far more precise estimate of the average risk to women with the genes. Around a half of the women in the analysis had no strong family history of breast or ovarian cancer.
They looked at the incidence of breast and ovarian cancer in relatives of the women. Using statistical techniques they calculated the average risk of developing breast or ovarian cancer up to age 70 for women with the damaged BRCA1 or BRCA2 genes.
Researchers found the average risk for a woman with a fault in BRCA1 was 65 per cent for breast cancer and 39 per cent for ovarian cancer- respectively 22 and 5 per cent age points lower than the previous estimates.
For women with a damaged version of BRCA2 the average risk was 45 per cent for breast cancer and 11 per cent for ovarian cancer – respectively 39 per cent and 16 per cent age points lower.
The researchers also found that risks estimates were higher when based on the families of breast cancer cases diagnosed below age 35. There was also some evidence that risks are higher for women born after 1960. This suggests that other genes and lifestyle or environmental factors can affect the risks.
Dr Pharoah, of the Cancer Research UK Genetic Epidemiology Unit at the University of Cambridge says: “Previous estimates for cancer risk to women with a faulty version of BRCA1 or BRCA2 have been very high because they are based on women with a strong family history of breast or ovarian cancer, who may have other genes or lifestyle factors contributing to their risk.
“Though attempts have been made to calculate the average risk to women in the population, studies have been small and the results unreliable. So there has been a gap in the information available to women with the damaged genes.
“Our study has pooled data from a large number of studies to ensure we have the most accurate estimate of risk to date.
“The results mean doctors will now be able to assess a woman’s risk based on her individual family history. The risk we have calculated can be used to counsel women who have one or no family members affected by breast or ovarian cancer and existing estimates can be used for women with a strong family history of either disease.”
Dr Lesley Walker, Director of Cancer Information at Cancer Research UK says: “Women found to have faulty versions of BRCA1 or BRCA2 are faced with difficult decisions about the options for reducing their risk of breast or ovarian cancer. They may consider surgery to try and prevent the development of these diseases or they could decide to go for regular screening and be monitored closely for the early signs of cancer. Alternatively they may opt to take drugs like tamoxifen, which have been shown to help prevent breast cancer. Their decisions are strongly influenced by the risks involved so a more accurate estimate based on family history will be very helpful.”
- American Journal of Human Genetics72 (5)
Around 1 in 1,000 women in the UK carry a damaged version of the BRCA1 gene and 1 in 700 carry a faulty BRCA2 gene.
Over 80% of families with four or more cases of breast or ovarian cancer under the age of 60 are found to have a damaged version of BRCA1 or BRCA2.
Faulty BRCA1 and BRCA2 genes are present in fewer families with less than 4 cases of breast or ovarian cancer and overall account for less than 5% of all breast cancer cases.