Two large studies provide a much sharper picture of hereditary mutations that increase the risk of breast cancer for women without a family history of the disease, and how common these defective genes are in the general population.
According to doctors, the results, published Wednesday by the New England Journal of Medicine, could help women make better decisions about examinations, preventative surgery or other steps.
Although these types of genetic tests are not currently recommended for the general population, they are increasing in use and many people get them 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 scientist from the University of Washington, did not play a role in the new studies, but discovered the first gene for breast cancer, BRCA1.
“The lives of many women can be saved if all women are given the opportunity to learn if they carry mutations in these genes before being diagnosed with cancer,” she wrote.
The American Cancer Society estimates that last year, 276,000 new cases of breast cancer were diagnosed in the United States. 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 comes mainly from studies of women with a family history of breast cancer or unusual situations such as getting it at a very young age. Little work has been done on specific mutations in these genes and how much each affects the chance of developing disease. The new studies fill some of these gaps.
One of them 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 Research Breast Cancer Research Foundation.
They searched for mutations in 12 genes linked to breast cancer in more than 64,000 women, about half with the disease and half without, which combined the results of 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 in 1.63% of the control group.
“Now we realize that 2% of women who roam the United States may have mutations in these genes,” Couch said.
There were no differences between racial groups in the chance that they generally had mutation, but certain mutations were more common in certain groups. For example, black women are more likely to have cancer linked to ‘triple negative’ cancers – tumors that are not fueled by estrogen or progesterone, or the gene targeted by the drug Herceptin.
The study also found that a mutation in the BRCA1 gene increased the risk of breast cancer almost eightfold, and in the BRCA2 gene more than fivefold.
Conversely, another’s opinion is not very worrying, but ‘what we have found is that it really has a low risk … people really should not react to it,’ Couch said.
Surgery may include more frequent mammograms or other screening tests, having breasts or ovaries removed, having family members tested or taking other steps.
With the new job, “we offer more accurate risk reports” 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 people with breast cancer and 53,000 similar without it.
“They found what we found” – increased risk of certain genes and a similar prevalence of them in the general population, Couch said.