MRI may lower breast cancer death from variants in 3 genes

March 3, 2022

Annual MRI screenings starting at ages 30 to 35 may reduce breast-cancer mortality by more than 50% among women who carry certain genetic changes in three genes, according to a comparative modeling analysis by the University of Washington.

The predictions involve pathogenic variants in ATM, CHEK2 and PALB2 genes – which collectively are as prevalent as the much-reported BRCA1/2 gene mutations. Authors of the study, published in JAMA Oncology, contend that their findings support MRI screening in some women earlier than existing guidelines propose.

“Screening guidelines have been difficult to develop for these women because there haven’t been clinical trials to inform when to start and how to screen,” said Kathryn Lowry, MD, an assistant professor of radiology at the University of Washington School of Medicine, the paper’s lead author.

Using established breast-cancer simulation models, the researchers input age-specific risk estimates provided by CARRIERS and recent published data for screening performance. The CARRIERS data involved more than 32,000 breast-cancer patients and a similar number of patients who had no cancer.

“For women with pathogenic variants in these genes, our modeling analysis predicted a lifetime risk of developing breast cancer at 21% to 40%, depending on the variant,” Lowry said. “We project that starting annual MRI screening at age 30 to 35, with annual mammography starting at age 40, will reduce cancer mortality for these populations of women by more than 50%.”

The simulations compared the combined performance of mammography and MRI against mammography alone and projected that annual MRI conferred significant additional benefit to these populations.

To realize a benefit of cancer screening guidelines based on genetic susceptibility, a woman would need to know she carries an implicated gene variant before receiving a disease diagnosis. More often it’s the case that a genetic test panel is administered after someone tests positive for cancer – too late to be of preventive value for the patient but potentially lifesaving for blood relatives who could seek genetic testing.

“People understand very well the value of testing for variants in BRCA1 and BRCA2, the most common breast cancer predisposition genes. These results show that testing other genes, like ATM, CHEK2, and PALB2, can also lead to improved outcomes,” said Mark Robson, PhD. He is chief of Breast Medicine Service at the Memorial Sloan Kettering Cancer Center and a senior author on the paper.

The researchers hope their analysis will aid the National Comprehensive Cancer Network (NCCN), the American Cancer Society and other organizations that issue guidance for medical oncologists and radiologists.

UW Medical release