Breast cancer screening with digital breast tomosynthesis plus synthesized two-dimensional mammography resulted in fewer invasive interval breast cancers over 2 years than standard digital mammography, although the difference did not reach statistical significance. Weigel et al reported the 24-month follow-up results of the randomized TOSYMA trial in The Lancet Oncology.
Digital breast tomosynthesis produces a series of low-dose x-ray images that can reduce the masking effect of overlapping breast tissue. Previous results from TOSYMA showed that the approach detected more invasive breast cancers during screening than standard digital mammography. The current analysis examined whether that higher detection rate translated into fewer invasive cancers diagnosed between screening rounds.
Study Details
TOSYMA was a multicenter, open-label, randomized trial conducted at 17 breast cancer screening sites in Germany. Women aged 50 to 70 years were randomly assigned to one round of screening with digital breast tomosynthesis plus synthesized two-dimensional mammography or standard digital mammography.
The current TOSYMA-2 analysis included 98,755 women who had a negative initial screening result: 49,299 in the tomosynthesis group and 49,456 in the digital mammography group. Median age was 57 years.
The primary endpoint was the rate of invasive interval breast cancer diagnosed within 24 months after a negative screening examination. Interval cancers were identified through linkage with regional cancer registries.
Key Findings
Over 24 months, invasive interval breast cancers were diagnosed in 70 women in the tomosynthesis group and 92 in the digital mammography group. That corresponded to rates of 14.2 vs 18.6 cases per 10,000 women with a negative screening result.
The 24% relative reduction with tomosynthesis did not reach statistical significance (OR = 0.76; P = .11).
During the first 12 months after screening, invasive interval cancers occurred in 22 women in the tomosynthesis group and 31 in the digital mammography group, corresponding to rates of 4.5 vs 6.3 cases per 10,000 women (OR = 0.71).
The difference over 24 months appeared more pronounced among women returning for a subsequent screening round. In that group, invasive interval cancer rates were 13.5 per 10,000 with tomosynthesis and 18.8 per 10,000 with digital mammography. Rates were nearly identical between the two screening approaches among women undergoing their first screening round.
When cancers detected during the initial screening round and the subsequent 24-month interval were considered together, sensitivity for invasive breast cancer was 83.5% with tomosynthesis plus synthesized two-dimensional mammography compared with 72.3% with digital mammography. Specificity was similar between groups.
The investigators noted that COVID-19 disruptions reduced enrollment below the planned sample size, which may have limited the trial’s ability to detect a significant difference.
“TOSYMA-2 indicates that about a quarter of invasive interval cancers occurring with digital mammography over 2 years might be avoided with digital breast tomosynthesis plus [synthesized two-dimensional] mammography screening,” they wrote.
Additional follow-up through the next screening round is planned to evaluate cumulative breast cancer incidence and differences in advanced-stage disease.
Walter Heindel, MD, of the University of Münster and University Hospital Münster, is the corresponding author.
DISCLOSURE: The study was funded by the German Research Foundation. For full disclosures of the study authors, visit thelancet.com.
