Credit: Dr. Kathyrn Lowry
Annual MRI screenings starting at ages 30 to 35 may slash breast-cancer mortality by more than 50% among women with genetic changes in three genes, according to a study published in JAMA Oncology.
The pathogenic variants are in the ATM, CHEK2 and PALB2 genes – which collectively are as prevalent as the much-reported BRCA1/2 gene mutations. The study authors state that their findings support earlier MRI screening in these women.
“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 lead author Dr Kathryn Lowry.
The work was a collaboration of the Cancer Intervention and Surveillance Modeling Network (CISNET), the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium, and the Breast Cancer Surveillance Consortium.
To arrive at their model, the researchers input age-specific risk estimates from CARRIERS involving some 64 000 women and recent published data for screening performance.
“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,” Dr 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.
“We also found that starting mammograms earlier than age 40 did not have a meaningful benefit but increased false-positive screens,” Dr Lowry added.
Results from CISNET models have informed past guidelines, including the 2009 and 2016 U.S. Preventive Services Task Force recommendations for breast cancer screening in average-risk women.
“Modelling is a powerful tool to synthesise and extend clinical trial and national cohort data to estimate the benefits and harms of different cancer control strategies at population levels,” said senior author Dr Jeanne Mandelblatt.
The study projected about four false-positive screening results and one to two benign biopsies per woman over a 40-year screening span, the authors noted.
To get any benefit from genetic susceptibility-based screening guidelines, a woman would have to know beforehand that she carries the gene, yet most often a genetic test panel is done after a positive cancer result – too late for any benefit.
“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 senior author Dr Mark Robson.
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.
“Overall what we’re proposing is slightly earlier screening than what the current guidelines suggest for some women with these variants,” said senior author Professor Allison Kurian. “For example, current NCCN guidelines recommend starting at age 30 for women with PALB2, and at 40 for ATM and CHEK2. Our results suggest that starting MRI at age 30 to 35 appears beneficial for women with any of the three variants.”
Source: University of Washington
