By Rebecca B. Perkins, MD, MSc
Professor, Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center, Boston
SYNOPSIS: This cohort study examined rates of advanced breast cancer diagnosis among women screened with digital mammography and digital breast tomosynthesis (DBT). Women with extremely dense breasts and who were at high risk for breast cancer benefited from DBT, with a 53% lower risk of developing advanced cancer compared to those screened with digital mammography alone. No differences were seen for women at low to average risk.
SOURCE: Kerlikowske K, Su Y-R, Sprague BL, et al. Association of screening with digital breast tomosynthesis vs digital mammography with risk of interval invasive and advanced breast cancer. JAMA 2022;327:2220-2230.
Breast cancer is the most common cancer diagnosed among women in the United States and the second leading cause of cancer death.1 Mammography has allowed earlier cancer diagnosis, leading to a reduction in cancer death in screened populations. A recent Swedish study noted a 25% reduction in advanced cancers and a 41% reduction in breast cancer death within 10 years among women who participated in screening compared to those who did not.2 Different risk factors have been associated with an increased risk of breast cancer, including age, family history, history of breast biopsy, and breast density on mammography.3 Because digital mammography may allow for better tumor identification and localization, especially among women with dense breasts, more centers have adopted digital breast tomosynthesis (DBT).4 However, questions have been raised about the benefits of DBT above standard digital mammography and whether certain groups of patients will benefit more than others.
This study by Kerlikowske and colleagues examined the risk of advanced breast cancer diagnosis (stage II or higher) among a cohort of approximately 500,000 women ages 40-79 years who underwent breast cancer screening between 2011 and 2018. Approximately 1 million women received digital mammography and 375,000 received DBT. Breast density was assessed using Breast Imaging Reporting and Data System (BIRADS) categories: almost entirely fatty, scattered fibroglandular densities, heterogeneously dense, and extremely dense. Breast cancer risk was categorized using the Breast Cancer Surveillance Consortium (BCSC) risk calculator version 2 (https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm). Risk levels included were low to average (≤ 1.66%), intermediate (1.67% to 2.49%), and high to very high (> 2.50%). To better assess prevention of advanced cancers, women were not included if cancer was diagnosed on their first mammogram, since this would indicate a cancer that already was present, which would preclude the ability to assess whether prior screening might have affected the diagnosis. On average, each woman in the study had two mammograms.
The study found that, overall, women screened with DBT had fewer advanced cancers diagnosed (0.36 vs. 0.45 per 1,000 examinations; difference, -0.09; 95% confidence interval [CI], -0.18 to -0.01) and fewer false-positive results (false-positive recalls [66.2 vs. 83.4; difference, -17.2; 95% CI, -25.2 to -9.2], and false-positive short-interval follow-up recommendations [11.2 vs. 17.9; difference, -6.7; 95% CI, -11.2 to -2.2]) compared to women screened with digital mammography. The greatest benefit in reduction of advanced cancer diagnoses was among women with extremely dense breasts and high cancer risk (0.27 vs. 0.80 per 1,000 examinations; difference, -0.53; 95% CI, -0.97 to -0.10). Findings were heterogenous among other combinations of breast density and risk level.
COMMENTARY
This study indicates that DBT may have advantages over digital mammography in terms of reducing advanced cancer diagnoses for high-risk women with extremely dense breasts. For a general screening population, DBT may reduce false-positive results. Currently, approximately 45% of breast cancer screening centers in the United States offer DBT and the remainder offer digital mammography. This study indicates that advanced cancer detection is unaffected by screening modality for > 95% of women. The results of the study suggest that, when both modalities are available, women with extremely dense breasts and a high risk of cancer may benefit from DBT over digital mammography. High risk in this study was defined using the BCSC risk calculator version 2, which takes into account risk factors, including age, race/ethnicity, family history, breast biopsy history, and breast density.
Breast cancer screening reduces the risk of cancer death by approximately 15% to 40%, depending on the population studied.5 In general, women 50-70 years of age have the largest reductions in cancer death, while younger women have the largest gains in years of life. Because current breast cancer screening requires frequent exams, has a substantial rate of false-positive results, and yields relatively modest reductions in cancer death, technologies that may improve diagnosis are needed. DBT appears to provide some advantages over digital mammography, although these primarily are realized in the 3.6% of women with extremely dense breasts and a high risk of breast cancer. In addition, DBT exposes the breast to a modestly higher radiation dose than digital mammography, the effects of which over 30 years of screening are unknown.6
Overall, strong evidence indicates that breast cancer screening reduces advanced cancers and saves lives.5 The study by Kerlikowske and colleagues indicates that DBT may have advantages for all screening populations in terms of reducing false-positive results and may benefit high-risk patients with extremely dense breasts by also reducing advanced cancer diagnoses. However, many questions remain, including the role of other modalities, such as magnetic resonance imaging and ultrasound.7 Research also is underway examining other biomarkers, although none currently are available outside of clinical research.8,9
REFERENCES
- American Cancer Society. Cancer facts and statistics. https://www.cancer.org/research/cancer-facts-statistics.html#:~:text=Breast%20cancer%20is%20the%20most,among%20women%20after%20lung%20cancer
- Duffy SW, Tabár L, Yen AM-F, et al. Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women. Cancer 2020;126:2971-2979.
- Rojas K, Stuckey A. Breast cancer epidemiology and risk factors. Clin Obstet Gynecol 2016;59:651-672.
- Chong A, Weinstein SP, McDonald ES, Conant EF. Digital breast tomosynthesis: Concepts and clinical practice. Radiology 2019;292:1-14.
- Siu AL, U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2016;164:279-296.
- Gennaro G, Bernardi D, Houssami N. Radiation dose with digital breast tomosynthesis compared to digital mammography: Per-view analysis. Eur Radiol 2018;28:573-581.
- Aristokli N, Polycarpou I, Themistocleous SC, et al. Comparison of the diagnostic performance of magnetic resonance imaging (MRI), ultrasound and mammography for detection of breast cancer based on tumor type, breast density and patient’s history: A review. Radiography (Lond) 2022; Feb 8:S1078-8174(22)00006-2. doi:10.1016/j.radi.2022.01.006. [Online ahead of print].
- Sauter ER. Using organ specific and circulatory biofluids to screen individuals at high risk for breast cancer presents unique challenges and opportunities. Cancer Epidemiol Biomarkers Prev 2021;30:429-431.
- Masood S. Development of a novel approach for breast cancer prediction and early detection using minimally invasive procedures and molecular analysis: How cytomorphology became a breast cancer risk predictor. Breast J 2015;21:82-96.
