Screening MRI may reduce breast cancer mortality in high-risk women: JAMA
USA: A modeling analysis suggests that in women with ATM, CHEK2, and PALB2 pathogenic variants, annual MRI screening starting at 30 to 35 years of age followed by annual MRI and mammography at 40 years may lessen breast cancer mortality by more than 50 percent. The study findings were published in the journal JAMA Oncology on February 17, 2022.
In women with the BRCA1 or BRCA2 mutations, adjunct screening with magnetic resonance imaging (MRI) is already recommended. ATM, CHEK2, and PALB2 are the most common of a more recently discovered group of pathogenic variants that confers a moderate to high breast cancer risk. Screening mammography and MRI although is recommended for women with ATM, CHEK2, and PALB2 pathogenic variants, there is not much data to guide screening regimens for these women.
Against the above background, Kathryn P. Lowry, University of Washington, Seattle Cancer Care Alliance, Seattle, and colleagues aimed to estimate the benefits and harms of breast cancer screening strategies using mammography and MRI at various start ages for women with ATM, CHEK2, and PALB2 pathogenic variants in a comparative modeling analysis.
For this purpose, the researchers used 2 established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. Using aggregated data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32 247 cases and 32 544 controls in 12 population-based studies, age-specific breast cancer risks were estimated.
Using published literature, the researchers estimated data on screening performance for mammography and MRI. The models simulated US women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985.
Interventions were screening strategies with combinations of annual mammography alone and with MRI starting at age 25, 30, 35, or 40 years until age 74 years.
Following were the study's key findings:
- The mean model-estimated lifetime breast cancer risk was 20.9% for women with ATM pathogenic variants, 27.6% for women with CHEK2 pathogenic variants, and 39.5% for women with PALB2 pathogenic variants.
- Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% to 38.5% compared with no screening.
- Screening with annual MRI starting at 35 years followed by annual mammography and MRI at 40 years was estimated to reduce breast cancer mortality by 54.4% to 57.6%, with 4661 to 5001 false-positive screenings and 1280 to 1368 benign biopsies per 1000 women.
- Annual MRI starting at 30 years followed by mammography and MRI at 40 years was estimated to reduce mortality by 55.4% to 59.5%, with 5075 to 5415 false-positive screenings and 1439 to 1528 benign biopsies per 1000 women.
- When starting MRI at 30 years, initiating annual mammography starting at 30 vs 40 years did not meaningfully reduce mean mortality rates (0.1% to 0.3%) but was estimated to add 649 to 650 false-positive screenings and 58 to 59 benign biopsies per 1000 women.
"These findings suggest that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may lessen breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants," wrote the authors. "In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit."
Reference:
Lowry KP, Geuzinge HA, Stout NK, et al. Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants: A Comparative Modeling Analysis. JAMA Oncol. Published online February 17, 2022. doi:10.1001/jamaoncol.2021.6204
KEYWORDS: JAMA Oncology, MRI screening, breast cancer, mortality, pathogenic variants, screening, Kathryn P Lowry, ATM, CHEK2, PALB2, mammography, jama, MRI, magnetic resonance imaging
