Two large studies paint a much sharper picture of the mutations in inheritance raising the risk of breast cancer in women without a family history of the disease
Two large studies paint a much sharper picture of whether hereditary mutations increase the risk of breast cancer in women without a family history of the disease, and the prevalence of these defective genes in the general population.
Doctors say the findings published Wednesday by the New England Journal of Medicine may help women make better decisions about screening, preventive surgery or other measures.
Although this type of genetic testing is not recommended for the general population, the use is growing and many people are getting it from tests that are sold directly to consumers.
The new work shows that the risk posed by some genes is “very high,” Mary-Claire King wrote in an email. King, a Washington University scientist, played no part in the new studies but discovered his first breast cancer predisposition gene, BRCA1.
“Many women’s lives could be saved if all women had the opportunity to learn if 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 gene mutations that raise the risk of developing the disease.
To date, what has been known about inherited risk has largely come from studies of women with a family history of breast cancer or unusual conditions such as getting it at a very young age. Little work has also been done on specific mutations in these genes and what effect each has on the development of disease. 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 supported the study with the Breast Cancer Research Foundation.
They looked for any mutations in 12 genes linked to breast cancer in more than 64,000 women, about half with the disease and half without, collecting results from studies across the United States including some in certain minority groups such as Blacks.
They found problematic mutations in about 5% of women with the disease and in 1.63% of the comparison group.
“We now understand that 2% of women who walk around in the United States may have mutations in these genes,” Couch said.
There were no differences among racial groups against mutation as a whole, but mutations were more common in some groups. For example, black women were more likely to be associated with “triple-negative” cancers – tumors that are not triggered by estrogen or progesterone, or the gene that the drug Herceptin targets.
The study also found that a mutation in the BRCA1 gene increased the risk of developing breast cancer by nearly eight times, and in the BRCA2 gene, more than five times.
On the other hand, another gene is thought to be very worrying but “what we have found is that it is low risk … humans should not be working on it,” Couch said.
Activities may include more frequent mammograms or other screening tests, with breast or ovaries removed, by family members to confirm or other measures.
With the new work, “we are providing more accurate risk estimates” to guide such decisions, Couch said.
The second study, led by researchers at Cambridge University in England, looked at 34 genes in women across the UK, Europe, Australia and Asia – around 60,000 with breast cancer and 53,000 similar ones without.
“They found what we found” – increased risk from specific genes and similar frequencies in the general population, Couch said.
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