Breast cancer screening: Does tomosynthesis augment mammography?

The Oslo trial: Limited applicability in USA

In April 2013, the Oslo tomosynthesis screening trial published interim results of its prospective cohort study of 12,631 Norwegian women ages 50 to 69.⁵ Women were invited to participate based on the availability of technical staff and imaging systems at the time of screening, and all participants underwent digital mammography and DBT. Images were read independently by 4 radiologists using a double-reader protocol.

The interim results suggest that adding DBT to digital mammography increased cancer detection rates by 31% and decreased the false-positive rate by 13% compared with 2D digital mammography alone (Table 1). However, the double-reader protocol in this study differs from typical single-reader protocols in the United States, limiting the applicability of the findings.

The STORM trial: Low sensitivity

The STORM trial is a prospective cohort study that included 7,292 women without symptoms, at average risk, age 48 and older, who participated in national breast cancer screening services in northern Italy. Each participant underwent digital mammography and DBT. The examinations were read sequentially (digital mammography first, then DBT plus digital mammography) either by a single radiologist, as is most common in the United States, or by 2 radiologists, as is standard in Europe.

Using the single-reader strategy, adding DBT significantly increased cancer detection rates and reduced the total recall rate (Table 1). Sensitivity was 85% vs 54%, and specificity was 97% vs 96%.^8,9

Of note, the sensitivity of 54% for digital mammography in the STORM trial is substantially lower than the sensitivity of digital mammography reported in the United States.¹⁰

Friedewald et al confirmed Oslo and STORM

To date, the largest US study of DBT plus digital mammography for breast cancer screening was a multicenter retrospective cohort study by Friedewald et al in 2014.¹¹ This study compared cancer detection and recall rates before and after the implementation of DBT at 13 breast centers and evaluated a total of 454,850 examinations (173,663 with DBT plus digital mammography and 281,187 with digital mammography only).

Overall, the recall rate decreased significantly after DBT was adopted and the cancer detection rate increased, findings consistent with those of the STORM and Oslo trials (Table 1). Adding DBT detected invasive cancers at a higher rate than 2D digital mammography alone (4.1/1000 vs 2.9/1,000), while there was no significant difference in ductal carcinoma in situ detection rates. This suggests that the additional cancers detected by DBT may be more clinically important. Nevertheless, the number of biopsies with negative results also increased, suggesting that adding DBT may pose potential harms.

In 2016, Rafferty et al¹² published an additional analysis of the data from Friedewald et al, concluding that adding DBT to 2D digital mammography increased the cancer detection rate more in women with heterogeneously dense breasts than in those with either nondense breasts or extremely dense breasts.¹² The reduction in recall rate was also greatest in the heterogeneously dense subgroup.

Insufficient evidence to recommend

Most other cohort studies comparing DBT and digital mammography have had findings similar to those of the European prospective studies and the large US retrospective cohort study, with the addition of DBT to mammography reducing recall rates and increasing cancer detection rates.¹³ However, many of these studies were subject to potential selection bias and did not provide information on the cancer risk of the participants. In addition, no studies have assessed clinical outcomes such as breast cancer stage at diagnosis or interval cancers, let alone breast cancer mortality.

Rigorous studies need to be done in the United States, using the standard single-reader protocol most often used in this country, to ascertain the clinical outcomes of DBT plus digital mammography for breast cancer screening for women at average risk. A 2016 review cited a dearth of high-quality US studies assessing the role of DBT in primary breast cancer.¹³

The US Preventive Services Task Force, in its 2016 guidelines for breast cancer screening, concluded that there was insufficient evidence to assess the harms and benefits of DBT as a method of breast cancer screening, including adjunctive screening in women with dense breasts.¹

Similarly, the American College of Physicians has advised against screening average-risk women for breast cancer using DBT.¹⁴

APPROVAL, DISSEMINATION, COSTS, AND CHOICE FOR PATIENTS

Even with early promising data suggesting that DBT can increase cancer detection rates and decrease false-positive results when added to routine screening mammography, the rapid diffusion of DBT into clinical practice is outpacing evidence of its effectiveness.⁴ This adoption was spurred in January 2015 when the Centers for Medicare and Medicaid Services added a Current Procedural Terminology code for DBT, allowing for additional reimbursement for it for all mammography indications.¹⁵ Still, the use of DBT in community settings is inconsistent, given the significant up-front costs associated with equipment purchases and variable reimbursement by private insurers who consider the technology experimental.

For the US healthcare system as a whole, it is uncertain whether the purported benefits of DBT will outweigh the additional costs associated with its use. The average reimbursement for a routine digital mammography examination is $135; adding DBT adds an average of $56 to the cost.¹⁵

Using an established, discrete-event breast cancer simulation model, a team of investigators evaluated the cost-effectiveness of combined biennial digital mammography and DBT screening compared with biennial digital mammography screening alone in US women with dense breasts.¹⁶ They found that biennial combined screening is likely to be cost-effective in US women with dense breasts. They also found that for every 2,000 women screened from age 50 to age 74, adding DBT would prevent 1 breast cancer death and 810 false-positive screening examinations.¹⁶

In addition, some have expressed concern that adding DBT to standard digital mammography increases radiation exposure. In fact, the radiation dose with DBT is similar to that with standard 2D digital mammography. Thus, when acquired together, combined digital mammography and DBT screening leads to twice the radiation dose compared with digital mammography alone.¹⁷ Nevertheless, this increased dose remains well below the FDA limits for a screening examination. In addition, the FDA has approved software that allows reconstruction of 2D synthetic views from the 3D data set, which will eventually bring radiation dose levels down to levels comparable to those of conventional digital mammography.¹⁷

Given that DBT is built into newer mammography units and is available as an add-on feature for existing units, its use is likely to increase even faster than digital mammography did when it replaced screen-film mammography in the previous decade.⁴ Its adoption by screening facilities, however, remains variable, and patients wishing to obtain combined DBT and digital mammography screening may have to travel to a different facility from their usual place of screening.¹⁸

Moreover, not all insurance companies cover DBT, resulting in additional out-of-pocket costs to the patient. It is currently unclear how individual facilities are offering DBT services, including how patients are selected for additional DBT and if they are offered the choice to add or forego DBT screening in combination with standard digital mammography.

SUMMARY: AN EMERGING TECHNOLOGY

DBT is an emerging imaging technology that allows the radiologist to view breast images in slices, as in computed tomography. DBT images can be obtained using the same breast compression that women already undergo for 2D digital mammography for breast cancer screening.

At this time, adding DBT to digital mammography screening nearly doubles the radiation exposure to the patient. However, new software is available that allows creation of synthetic 2D views from the 3D data set, resulting in radiation exposure that is similar to conventional digital mammography.

Although there are no published randomized controlled trials assessing the benefit of DBT over 2D digital mammography for breast cancer screening, prospective observational studies suggest that DBT may reduce false-positive recall rates and increase cancer detection rates when used in population-based screening programs. Assuming that additional breast cancer detection contributes to improved clinical outcomes, women with dense breasts may benefit more than women without dense breasts.

No national organizations currently recommend DBT for primary breast cancer screening. Ideally, future studies would determine whether DBT screening reduces breast cancer mortality. Since this research may not be feasible, surrogate clinical outcomes, such as a decrease in interval breast cancer rates and impact on stage at time of diagnosis, would allow us to more confidently recommend this new technology.