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Lifetime cancer risk predicted for BRCA mutation carriers

26 June 2017

By Lea Goetz

Appeared in BioNews 906

A study of almost 10,000 women carrying BRCA mutations has revealed the best estimate yet of their risk in developing breast and ovarian cancer.

The scientists say the findings could help clinicians decide on cancer screening timelines and prevention strategies for BRCA mutation carriers.

'This is the largest and most scientifically rigorous study to date without question,' said Professor Kelly-Anne Phillips of the Peter Mac Breast and Ovarian Cancer Risk Management Clinic. 'We used data from a large number of studies running internationally'.

BRCA1 and BRCA2 mutations can increase the risk of breast cancer five-fold and ovarian cancer up to 30 fold, depending on the exact type of the mutation and its location within the gene. However previous studies have produced a wide variation in cumulative risk estimates for breast and ovarian cancer, and most studies have only looked at carriers who have already developed cancer.

The new study, led by the University of Melbourne and Cancer Council Victoria, Australia, recruited almost 10,000 women from Europe, the United States, Canada, Australia and New Zealand through three consortia. Of the 6036 women carrying the BRCA1 and 3820 women carrying the BRCA2 mutation, almost half had breast or ovarian cancer or both at study's onset. The researchers established each participant's family history of cancer and the exact location of their mutation before following them for an average of five years.

They found that BRCA1 carriers were most likely to develop breast cancer in their 30s and BRCA2 carriers in their 40s. The lifetime breast cancer risk was 72 percent for BRCA1 and 69 for BRCA2 carriers, with risks remaining high until age 80. This finding contradicts previous thinking that risk is reduced if a carrier reaches 60 without a cancer diagnosis.

For ovarian cancer the risk was 44 percent for BRCA1 and 17 percent for BRCA2 carriers.

Other key findings included the discovery that carriers were at higher risk of both cancers if they had first- and second-degree relatives with breast cancer. The risk could also be doubled if the mutations were in specific regions of the BRCA1 or BRCA2 genes.

Women who have had cancer in one of their breasts had a cumulative risk of 40 percent for BRCA1 and 26 percent for BRCA2 of developing cancer in the other breast after 20 years.

'We have been able to provide the most precise estimates of age-specific risks to date,' said lead author Dr Antonis Antoniou of the University of Cambridge. 'These should provide more confidence in the counselling and clinical management of women with faults in the BRCA1 and BRCA2 genes.'

The researchers caution however that they did not distinguish between different breast and ovarian cancer tumour phenotype in their study, or the effect of certain medications to reduce risk of breast cancer. Furthermore, the study participants were not identified through population screening of unaffected women, and so the risk estimates are not representative for all women.

The study was published in JAMA.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

09 October 2017 - by Dr Loredana Guglielmi 
A major breakthrough in understanding how mutations in the BRCA1 gene raise cancer risk has been made by researchers in the USA...

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A common chemical found in household products could increase the risk of cancer by blocking the ability of cells to fix genetic flaws which lead to the disease...
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A genetic study of breast cancer patients suggests that existing drugs for treating rare breast and ovarian cancers may help more patients than previously thought...
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A study has indicated that US doctors may not be recommending genetic testing to a sufficient number of high-risk breast cancer patients...
19 December 2016 - by Anastassia Bolotkova 
Angelina Jolie's 2013 public announcement that she has the BRCA1</i> breast cancer gene led to a 64 percent increase in women seeking genetic testing for breast cancer...

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