• Karla Kerlikowske, Yu-Ru Su, Brian L Sprague, TostesonAnna N AANAThe Dartmouth Institute for Health Policy and Clinical Practice and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire., BuistDiana S MDSMKaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle., Tracy Onega, Louise M Henderson, Nila Alsheik, Michael C S Bissell, Ellen S O'Meara, Christoph I Lee, and Diana L Miglioretti.
• Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco.
• JAMA. 2022 Jun 14; 327 (22): 222022302220-2230.

ImportanceDigital breast tomosynthesis (DBT) was developed with the expectation of improving cancer detection in women with dense breasts. Studies are needed to evaluate interval invasive and advanced breast cancer rates, intermediary outcomes related to breast cancer mortality, by breast density and breast cancer risk.ObjectiveTo evaluate whether DBT screening is associated with a lower likelihood of interval invasive cancer and advanced breast cancer compared with digital mammography by extent of breast density and breast cancer risk.Design, Setting, And ParticipantsCohort study of 504 427 women aged 40 to 79 years who underwent 1 003 900 screening digital mammography and 375 189 screening DBT examinations from 2011 through 2018 at 44 US Breast Cancer Surveillance Consortium (BCSC) facilities with follow-up for cancer diagnoses through 2019 by linkage to state or regional cancer registries.ExposuresBreast Imaging Reporting and Data System (BI-RADS) breast density; BCSC 5-year breast cancer risk.Main Outcomes And MeasuresRates per 1000 examinations of interval invasive cancer within 12 months of screening mammography and advanced breast cancer (prognostic pathologic stage II or higher) within 12 months of screening mammography, both estimated with inverse probability weighting.ResultsAmong 504 427 women in the study population, the median age at time of mammography was 58 years (IQR, 50-65 years). Interval invasive cancer rates per 1000 examinations were not significantly different for DBT vs digital mammography (overall, 0.57 vs 0.61, respectively; difference, -0.04; 95% CI, -0.14 to 0.06; P = .43) or among all the 836 250 examinations with BCSC 5-year risk less than 1.67% (low to average-risk) or all the 413 061 examinations with BCSC 5-year risk of 1.67% or higher (high risk) across breast density categories. Advanced cancer rates were not significantly different for DBT vs digital mammography among women at low to average risk or at high risk with almost entirely fatty, scattered fibroglandular densities, or heterogeneously dense breasts. Advanced cancer rates per 1000 examinations were significantly lower for DBT vs digital mammography for the 3.6% of women with extremely dense breasts and at high risk of breast cancer (13 291 examinations in the DBT group and 31 300 in the digital mammography group; 0.27 vs 0.80 per 1000 examinations; difference, -0.53; 95% CI, -0.97 to -0.10) but not for women at low to average risk (10 611 examinations in the DBT group and 37 796 in the digital mammography group; 0.54 vs 0.42 per 1000 examinations; difference, 0.12; 95% CI, -0.09 to 0.32).Conclusions And RelevanceScreening with DBT vs digital mammography was not associated with a significant difference in risk of interval invasive cancer and was associated with a significantly lower risk of advanced breast cancer among the 3.6% of women with extremely dense breasts and at high risk of breast cancer. No significant difference was observed in the 96.4% of women with nondense breasts, heterogeneously dense breasts, or with extremely dense breasts not at high risk.

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