Earlier MRI Screenings Could Significantly Cut Breast Cancer Mortality for Certain Pathogenic Variants

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Breast cancer mortality could be reduced by half for patients with ATM, CHEK2, and PALB2 pathogenic variants who undergo annual MRI screenings between the ages of 30 to 35 years and annual MRI screenings and mammography for those 40 or older.

Findings from an analysis indicated that annual MRI screenings in patients aged 30 to 35 years followed by annual MRI and mammography in those aged 40 years may reduce breast cancer mortality by 50% in patients with ATM, CHEK2, and PALB2 pathogenic variants.

The mean estimated lifetime breast cancer risk was 20.9% (95% CI, 18.1%-23.7%) for those with an ATM variant, 27.6% (95% CI, 23.4%-31.7%) with CHEK2, and 39.5% (95% CI, 35.6%-43.3%) for PALB2. Across all subgroups, annual mammography alone in patients 40 to 74 years was estimated to reduce disease-related mortality by 36.4% (95% CI, 34.6%-38.2%) to 38.5% (95% CI, 37.8%-39.2%) vs no screening. Additionally, breast cancer mortality was reduced by 54.4% (95% CI, 54.2%-54.7%) to 57.6% (95% CI, 57.2%-58.0%) in patients who received an annual MRI starting at 35 years followed by MRI and mammography at 40 years; a total of 4661 to 5001 false positive screenings and 1280 to 1368 benign biopsies per 1000 patients were reported.

Moreover, annual MRI at 30 years plus mammography and MRI at 40 years was estimated to reduce mortality by 55.4% (95% CI, 55.3%-55.4%) to 59.5% (95%, CI, 58.5%-60.4%); 5075 to 5415 false positive screenings and 1439 to 1528 benign biopsies per 1000 patients were reported. For those starting MRI at 30, initiating mammography at 30 years vs 40 years did not meaningfully reduce the rate of disease-related mortality (0.1%-0.3%), but added about 649 to 650 false positive screenings and 58 to 59 benign biopsies per 1000 patients.

The analysis modeled patients in the United States with ATM, CHEK2, or PALB2 pathogenic variants who were born in 1985 and observed from the age of 25 years through their lifetime. Data from the CARRIERS Consortium helped to set the parameters for breast cancer incidence and subtype. Investigators used data from 32,247 cases and 32,544 controls across 12 population-based studies. Investigators noted that population-based breast cancer risk studies are more generalizable vs studies that enrolled patients following genetic testing based on notable family history or young age at diagnosis.

The cumulative mean lifetime risk of disease-related mortality in the absence of screening across the ATM, CHEK2, and PALB2 groups, respectively were 3.4% (95% CI, 2.4%-4.5%), 4.6% (95% CI, 3.1%-6.1%), and 7.7% (95% CI, 6.4%-9.1%), respectively. Annual MRI screenings for patients aged 35 to 39 years plus mammography and MRI from 40 to 74 years was more efficient compared with annual mammography alone from age 40 to 74 years.

Reference

Lowry K, Geuzinge HA, Stout NK, et al. Breast cancer screening strategies for women with ATM, CHEK2, and PALB2 pathogenic variants. JAMA Oncol. 2022;8(4):587-596. doi:10.1001/jamaoncol.2021.6204

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