Two large studies provide a much clearer picture of which hereditary mutations increase the risk of breast cancer in women without a family history of the disease and how common these defective genes are in the general population.
Doctors say the results published on Wednesday by the New England Journal of Medicine may help women make better decisions about examinations, preventive surgery or other steps.
Although this type of genetic testing is not recommended for the general population, its use is growing and many people obtain it from tests sold directly to consumers.
The new work shows that the risk posed by some genes “is very high,” wrote Mary-Claire King in an email. King, a scientist at the University of Washington, had no role in the new studies, but discovered the first breast cancer predisposing gene, BRCA1.
“Many women’s lives could be saved if all women had the opportunity to know whether they carry mutations in these genes before being diagnosed with cancer,” she wrote.
The American Cancer Society estimates that 276,000 new cases of breast cancer were diagnosed in the United States last year. The new work suggests that at least 13,800 of them occur in women with inherited genetic mutations that increase the risk of developing the disease.
So far, what was known about hereditary risk has come largely from studies of women with a family history of breast cancer or from unusual situations, such as contracting cancer at a very young age. There has also been little work on specific mutations in these genes and how much each affects the chances of developing diseases. The new studies fill some of these gaps.
One was led by Fergus Couch, a pathologist at the Mayo Clinic and included researchers from the National Institutes of Health, who sponsored the study with the Breast Cancer Research Foundation.
They searched for any mutations in 12 genes that were associated with breast cancer in more than 64,000 women, about half with the disease and the other half without it, gathering results from studies in the United States, including some in specific minority groups, such as black people.
They found problematic mutations in about 5% of women with the disease and in 1.63% of the comparison group.
“Now we realize that 2% of women who walk around the United States can have mutations in these genes,” said Couch.
There were no differences between racial groups in the chances of having a general mutation, but certain mutations were more common in certain groups. For example, black women were more likely to have cancers associated with “triple negative” cancers – tumors that are not fueled by estrogen or progesterone, or by the gene that the Herceptin drug targets.
The study also found that a mutation in the BRCA1 gene increased the risk of developing breast cancer by almost eight times, and in the BRCA2 gene, by more than five times.
On the other hand, another gene was considered to be very worrying, but “what we found is that it is a very low risk … people really shouldn’t be acting on it,” said Couch.
Actions may include more frequent mammograms or other screening tests, removal of breasts or ovaries, exams of family members or other steps.
With the new work, “we are providing more accurate risk estimates” to guide such decisions, said Couch.
The second study, led by researchers at the University of Cambridge in England, looked at 34 genes in women across the UK, Europe, Australia and Asia – about 60,000 with breast cancer and 53,000 similar ones without it.
“They found what we found” – increased risk of certain genes and a similar prevalence of them in the general population, said Couch.
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