Two large studies provide a much clearer picture of which hereditary mutations increase breast cancer risk 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 Wednesday by the New England Journal of Medicine may help women make better decisions about screening, preventive surgery, or other steps.
While this type of genetic testing is not currently recommended for the general population, its use is on the rise and many people are getting it from tests sold directly to consumers.
The new work shows that the risk of some genes is “very high,” Mary-Claire King wrote in an email. King, a scientist at the University of Washington, was not involved in the new studies, but discovered the first gene for breast cancer, BRCA1.
“Many women’s lives could be saved if all women were given the opportunity to learn whether 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 their risk of developing the disease.
What is known so far about hereditary risk has largely come from studies involving women with a family history of breast cancer or unusual situations, such as getting breast cancer at a very young age. Little work has also been done on specific mutations in these genes and how much influence they have on the risk of developing a disease. The new studies fill in some of those 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 looked for mutations in 12 genes linked to breast cancer in more than 64,000 women, about half with the disease and the other half without, and gathered results from studies in the United States, including some in specific minority groups such as blacks.
They found troublesome mutations in about 5% of the women with the disease and 1.63% of the comparison group.
“Now we realize that 2% of women walking around the United States may have mutations in these genes,” said Couch.
There were no differences between racial groups in the probability of an overall mutation, but certain mutations were more common in certain groups. For example, black women were more likely to have cancers linked to “triple negative” cancers – tumors that aren’t fueled by estrogen or progesterone, or the gene targeted by the drug Herceptin.
The study also found that having a mutation in the BRCA1 gene nearly eight-folds the risk of developing breast cancer and more than fivefold in the BRCA2 gene.
Conversely, another gene is thought to be very concerning, but “what we found is that it’s really low risk … people really shouldn’t act on it,” Couch said.
Possible actions include more frequent mammograms or other screening tests, breast or ovary removal, having family members tested, or other steps.
With the new work, “we provide more accurate risk assessments” to guide such decisions, Couch said.
The second study, led by researchers at the University of Cambridge in England, looked at 34 genes in women in the UK, Europe, Australia and Asia – about 60,000 with breast cancer and 53,000 comparable without.
“They found what we found” – increased risk of certain genes and a similar prevalence of them in the general population, Couch said.