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William J. Gradishar, MD, FACP, FASCO


Breast Cancer With Certain Pathogenic Variants: What Is the Optimal Approach to Screening?

By: Victoria Kuhr, BA
Posted: Monday, March 28, 2022

Kathryn P. Lowry, MD, of Seattle Cancer Care Alliance, and colleagues propose that annual MRI screenings starting at age 30 to 35 may reduce breast cancer mortality in women with a moderate to high risk of breast cancer with ATM, CHEK2, and PALB2 pathogenic variants. Additionally, they suggest that starting mammogram screenings before age 40 may increase false-positive screenings and benign biopsies. These findings were published in JAMA Oncology.

“Screening guidelines have been difficult to develop for women with these genetic variants because there haven’t been clinical trials to inform when to start and how to screen,” said Dr. Lowry in a University of Washington School of Medicine press release. “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.”

This comparative modeling analysis used two established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. The study estimated age-specific breast cancer risks using aggregate data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32,247 patients with breast cancer and 32,544 patients without breast cancer in 12 population-based studies.

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 ages 40 to 74 was estimated to reduce breast cancer mortality by 36.4% to 38.5% compared with no screening. Screening with annual MRI starting at age 35 followed by annual mammography and MRI at age 40 was estimated to reduce breast cancer mortality by 54.4% to 57.6%. The study found 4,661 to 5,001 false-positive screenings, and 1,280 to 1,368 benign biopsies occurred per 1,000 women.

Disclosure: For full disclosures of the study authors, visit

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