In an analysis reported in JAMA Oncology, Lowry et al found that a strategy of annual magnetic resonance imaging (MRI) screening starting at age 30 to 35 years—followed by annual MRI and mammography at age 40—could reduce the risk of breast cancer mortality by more than 50% in women with ATM, CHEK2, and PALB2 pathogenic variants.
Study Details
The modeling analysis used two established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate screening strategies. Age-specific breast cancer risks were estimated using data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium, including 32,247 breast cancer cases and 32,544 controls from 12 population-based studies; data on screening performance for mammography and MRI were estimated from published literature. The models simulated U.S. women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985, using screening strategies with annual mammography and MRI starting at age 25, 30, 35, or 40 until age 74.
This analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.— Lowry et al
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Key Findings
The mean model-estimated lifetime breast cancer risk was 20.9% (range = 18.1%–23.7%) for women with ATM pathogenic variants, 27.6% (range = 23.4%–31.7%) for those with CHEK2 pathogenic variants, and 39.5% (range = 35.6%–43.3%) for those with PALB2 pathogenic variants.
Across pathogenic variants, annual mammography alone from age 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (range = 34.6%–38.2%) to 38.5% (range = 37.8%–39.2%) compared with no screening.
Across variants, annual MRI starting at age 35 years followed by annual mammography and MRI at age 40 years was estimated to reduce breast cancer mortality by 54.4% (range = 54.2%–54.7%) to 57.6% (range = 57.2%–58.0%), with 4,661 (range = 4,635–4,688) to 5,001 (range = 4,979–5,023) false-positive screenings and 1,280 (range = 1,272–1,287) to 1,368 (range = 1,362–1,374) benign biopsies per 1,000 women.
Across variants, annual MRI starting at age 30 years followed by mammography and MRI at age 40 years was estimated to reduce mortality by 55.4% (range = 55.3%–55.4%) to 59.5% (range = 58.5%–60.4%), with 5,075 (range = 5,057–5,093) to 5,415 (range = 5,393–5,437) false-positive screenings and 1,439 (range = 1,429–1,449) to 1,528 (range = 1,517–1,538) benign biopsies per 1,000 women.
Across variants, if annual MRI were started at age 30 years, annual mammography started at age 30 vs 40 years was estimated to reduce mean mortality rates by only 0.1% (range = 0.1%–0.2%) to 0.3% (range = 0.2%–0.3%), and was estimated to add 649 (range = 602–695) to 650 (range = 603–696) false-positive screenings and 58 (range = 41–76) to 59 (range = 41–76) benign biopsies per 1,000 women.
The investigators concluded, “This analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.”
Kathryn P. Lowry, MD, of the Department of Radiology, University of Washington, Seattle Cancer Care Alliance, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by grants from the National Cancer Institute, Breast Cancer Research Foundation, and others. For full disclosures of the study authors, visit jamanetwork.com.
