ToSyMa study results phase 1: +48% detection rate for invasive breast tumors indicates superiority of 3D mammography over standard 2D mammography.
Breast cancer is still the cancer with the highest mortality rate. 2D mammography screening is still the method of choice for effective early detection. Approximately 11.9 million* women aged 50-69 are entitled to screening with digital mammography every two years. However, in Germany only every second eligible woman accepts the invitation. Among the various reasons for refusal is, for example, concern about false positive findings (false alarm) or overdiagnosis. However, false negative findings in particular must also be prevented. In this context, one disadvantage of two-dimensional mammography is the superimposition of tissue structures, which makes it more difficult to find focal findings, according to the study group led by Prof. Walter Heindel. Tomosynthesis, or 3D mammography, solves this problem by providing a pseudo-3D view through the breast using 1mm slice radiographs. And although there have been several studies on the clinical superiority of tomosynthesis vs. 2D mammography, no large randomized, controlled, multi-center, device-independent study was available when the ToSyMa study was designed and is still available today.
The intended added value of the ToSyMa study to the existing evidence lies in its design as a randomized controlled multicenter superiority study, which is embedded in the setting of the highly quality-assured German governmental screening and is funded by the German Research Foundation DFG independently of the manufacturer. The design of the ToSyMa study was previously published in 2018. The acronym ToSyMa stands for “tomosynthesis (3D) and synthesized mammography (s2D)” – in contrast to the digital (2D) mammography used exclusively in German breast cancer screening to date.
The digital mammography devices used in the German screening units and 27 tomosynthesis devices from 5 manufacturers at 17 German screening sites were used and corresponded to the state of the art at the time of study initiation. Hologic is involved with 44% of the 3D devices.
Approximately 100,000 participants of the German breast cancer screening program aged 50-69 years were randomly assigned either to the intervention group with tomosynthesis (3D) including additional synthesized mammography (s2D) or to the control group with digital mammography (2D). In both arms, one CC and one MLO image per breast were obtained and evaluated by two independent radiologists.
Between July 5, 2019, and December 30, 2020, 49,804 women were assigned to the tomosynthesis (3D) group and 49,830 women were assigned to the digital mammography (2D) group.
The first clinical endpoint investigated was whether a relevant increase in invasive breast cancer detection rates is achieved with tomosynthesis compared to digital mammography (ToSyMa Phase 1). This phase is completed with publication in the Lancet April 2022.
As a further clinical endpoint, the occurrence of interval carcinomas in the interval of 24 months will be investigated in the two test arms (ToSyMa Phase 2). This will be based on evaluations of the German cancer registry. The software of the state screening documents interval carcinomas in the German cancer registry. The potential reduction in interval cancer rates will determine the incremental clinical benefit of tomosynthesis in breast cancer screening. Publication of these results is expected in early 2025.
Results ToSyMa Phase 1
The results of the ToSyMa phase 1 study indicate a superiority of 3D/s2D mammography compared to the standard, the study initiators conclude. An increase of 33% in the detection rate of invasive tumors had been estimated before the start of the study. With 48% (7.1 women per 1000) higher detection rate for in- vasive breast cancer than in the 2D control group, the 3D/s2D intervention group was significantly higher than expected (4.8 women per 1000). This is also in agreement with previous meta-analyses. The detection rate for invasive breast cancer with tomosynthesis and s2D was significantly higher compared with the control group, especially in women older than 60 years.
The mean reading time (median) of 109 seconds for the combination of 3D plus s2D was understandably higher than the mean reading time of 48 seconds in the control group 2D. The study group sees an explanation in the instruction to evaluate all 1mm slices plus the s2D, since the s2D is used as a comparison to previous images. Among others, artificial intelligence could optimize reporting time and cost efficiency in the future.
The results suggest that screening with tomosynthesis probably shows diagnostic improvements.
In a publication in the German journal Senologie the study investigators of the ToSyMa study summarize::
“In the ToSyMa study phase 1, the first primary hypothesis was confirmed that invasive breast cancer is detected significantly more often – exactly by 48% – in screening with the advanced mammography technique (tomosynthesis) than with standard mammography. … If can be shown in the ToSyMa phase 2 trial that further advancing breast cancer diagnosis decreases the number of interval cancers in the test arm compared to the control arm, a longer-term benefit of tomosynthesis in screening would be proven.”
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*based on population data in Germany
1) Mammography Cooperation Group, Annual Report Evaluation 2019 https://fachservice.mammo-programm.de/download/evaluationsberichte/ new_KOOPMAMMO_Annual_Report_Eval_2019_20211112_web-single_page.pdf.
2) Weigel S, Gerss J, Hense H, Krischke M, Sommer A, Czwoydzinski J, et al. Digital breast tomosynthesis plus synthesised images versus standard fullfield digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial. BMJ Open 2018;8:e020475. doi:10.1136/bmjopen-2017-020475.
3) Heindel W, Weigel S, Gerß J, Hense HW, Sommer A, Krischke M, et al. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2022 May; 23(5):601-611.
4) Freeman K, Geppert J, Stinton C, et al. Use of artificial intelligence for imaging analysis in breast cancer screening programmes: systematic review of test accuracy. BMJ 2021; 374: n1872
5) Heindel W, Weigel S. First results on the multicenter randomized controlled breast cancer diagnostic study ToSyMa. Senology 2022; 19: 125-126.
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