False-Positive Results of Mammography Screening in the Era of Digital Breast Tomosynthesis

Ho and colleagues¹ examine whether use of digital breast tomosynthesis (DBT), termed 3D mammography by some clinicians and patients, is associated with a lower probability of false-positive results over 10 years of screening compared with digital mammography. The authors used prospectively collected data from approximately 1 million women and almost 3 million mammograms performed at 126 radiology facilities participating in the Breast Cancer Surveillance Consortium to examine screening round–specific false-positive events (including recall for further imaging, short-interval follow-up recommendations, and biopsy recommendations) and cumulative false-positive event rates associated with annual or biennial screening with digital mammography or DBT, adjusting for age and breast density. The authors found that DBT was associated with fewer recalls for false-positive results over a 10-year study period, although the difference was modest: 10-year rates were 56.3% for annual screening with digital mammography vs 49.6% with annual DBT. Differences between DBT and digital mammography were smaller for short-interval follow-up and biopsy recommendations. Moreover, screening interval, age, and breast density were associated more than screening modality with false-positive rates. For women with the highest degree of breast density (ie, extremely dense breasts), false-positive rates were similar for DBT and digital mammography.

Much of what we know about the benefits and harms of mammography screening has come from studies of mammography technology that is no longer widely used (eg, plain film mammography), raising concerns that these estimates are not relevant for women undergoing mammograms today. Digital breast tomosynthesis, now widely used in the US,² has been associated with increased cancer detection and decreased recall rates,³ leading to optimism that DBT screening could lead to a more favorable ratio of benefits (ie, early detection of clinically meaningful breast cancers and ultimately reduced breast cancer mortality) to harms (including false-positive results). A previous multicenter study⁴ also suggested that women with dense breasts might experience a particularly favorable reduction in recall rates with DBT—an encouraging finding since digital mammography performs less well in dense breasts compared with nondense breasts, and greater breast density is also associated with a higher risk of breast cancer..

The current study by Ho and colleagues¹ may be the first study to calculate cumulative false-positive rates with DBT over a relatively long period of screening, providing important information to guide contemporary shared decision-making about whether to initiate mammography and how frequently to screen. Consistent with prior Breast Cancer Surveillance Consortium work,⁵ the risk of at least one false-positive recall over 10 years of screening was higher with annual than biennial (every 2 years) screening; this was true regardless of screening modality. The difference in recall rates with biennial digital mammography (38.1%) compared with biennial DBT (35.7%) was about half the difference noted with annual screening (56.3% vs 49.6%). The probability of false-positive results also varied markedly by decade of life, with the highest cumulative rates among women aged 40 to 49 years undergoing screening (68.0% with annual digital mammography and 60.8% with annual DBT).¹ As expected, false-positive results were consistently more likely among women with dense breasts. Digital breast tomosynthesis was associated with the greatest reduction in false-positive results among women with nondense breasts and was not associated with a reduction in false-positive rates for women with extremely dense breasts (67.3% vs 65.0%).

The current study’s findings of greater false-positive reductions for women with nondense breasts contrast with a previous multicenter study that found that DBT was associated with a greater reduction in false-positive results among women with dense breasts compared with those with nondense breasts.⁴ There are some important methodologic differences in the approach of Ho and colleagues¹ compared with prior studies examining DBT performance. In contrast to prior studies, the authors excluded baseline examinations, which are associated with greater false-positive rates than subsequent mammograms⁶ but also, by definition, occur in women’s younger years, complicating differentiation of the contributions of age and screening round. Although DBT may be associated with a greater reduction in false-positive rates when baseline mammograms are considered, this reduction appears not to be sustained with continued screening. In addition, most previous work has grouped heterogeneously and extremely dense breasts together. Women with extremely dense breasts are a smaller group, limiting analyses’ statistical power to detect differences, and the results of the current study should be interpreted with some caution as a result. However, women with dense breasts may derive less additional benefit from DBT. More research is urgently needed to inform better long-term screening strategies for women with dense breasts, particularly those with extremely dense breasts who have a 2-fold increased risk of developing breast cancer compared with women with nondense breasts.⁷

Overall, the results from this study¹ suggest that, unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms: with annual screening, about half of women undergoing screening with DBT will experience at least 1 false-positive recall. Although many women tolerate false-positive results, they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening, although with the greater cancer detection rate of DBT, it seems quite likely that DBT is associated with more overdiagnosis. Other downsides of DBT relative to standard digital mammography include its expense; DBT also can be associated with greater radiation exposure depending on the machine and protocol. Whether DBT achieves better breast cancer outcomes to offset these harms has not been definitively shown.

In the meantime, the study by Ho and colleagues¹ reminds us that even if we practice in a center where DBT is routinely offered, clinicians should continue to counsel patients that false-positive results are an expected outcome from mammography screening. This possibility is especially true if individuals have mammograms every year or start before age 50 years. The findings of Ho and colleagues¹ underscore that individual characteristics, such as age and breast density, along with other breast cancer risk factors, may affect whether a woman will derive net benefits from mammography screening and provide further evidence of the importance of an individualized approach to screening decisions.

Published: March 25, 2022. doi:10.1001/jamanetworkopen.2022.2445

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Pace LE. JAMA Network Open.

Corresponding Author: Lydia E. Pace, MD, MPH, Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115 (lpace@bwh.harvard.edu).

Conflict of Interest Disclosures: None reported.