Two large studies offer a much clearer view of what inherited mutations increase the risk of breast cancer for women without a family history of the disease and how often these defective genes are found in the general population.
Doctors say the results published Wednesday by the New England Journal of Medicine may help women make better decisions about screening, preventive surgery or other steps.
Although this type of genetic testing is not currently recommended for the general population, its use is growing and many people are getting it from tests 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 scientist at the University of Washington, played no role in the new studies, but discovered the first predisposing gene for breast cancer, BRCA1.
“Many women’s lives could be saved if all women were offered the opportunity to learn if they carry mutations in these genes before they are 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 increase the risk of developing the disease.
Until now, what was known about inherited risk has been largely from studies of women with a family history of breast cancer or unusual situations, such as suffering from it at a very early age. Little work has also been done on specific mutations in these genes and how much each affects the chances of developing diseases. 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 Foundation for Breast Cancer Research.
They looked for any mutations in 12 genes that have been linked to breast cancer in more than 64,000 women, about half with the disease and half without it, grouping the results of studies in the United States, including some into specific minority groups. like blacks.
They found problematic mutations in approximately 5% of women with the disease and in 1.63% of the comparison group.
“We now realize that 2% of women walking around the United States may have mutations in these genes,” Couch said.
There were no differences between racial groups in the probabilities of having a global mutation, but certain mutations were more common in certain groups. For example, black women were more likely to have “triple-negative” cancers: tumors that are not fed estrogen or progesterone, or the gene that targets the drug Herceptin.
The study also found that having a mutation in the BRCA1 gene increased the risk of developing breast cancer almost eight times, and in the BRCA2 gene, more than five.
By contrast, another gene has been considered very worrisome, but “what we’ve found is that it has a very low risk … people really shouldn’t act on it,” Couch said.
Actions may include more frequent mammograms or other screening tests, removal of breasts or ovaries, testing of family members, or other steps.
With the new work, “we provide more accurate risk estimates” to guide those decisions, Couch said.
The second study led by researchers at the University of Cambridge in England examined 34 genes in women across the UK, Europe, Australia and Asia, about 60,000 with breast cancer and 53,000 similar ones without.
“They found what we found”: increased risk of certain genes and a similar prevalence of them in the general population, Couch said.