The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.
The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.
“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.
“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.
In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.
However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.
“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”
The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.
Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.
The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.
The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.
However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.
As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”
Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.
Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.
“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”