Effectiveness of digital breast tomosynthesis (3D-mammography) in population breast cancer screening: A protocol for a collaborative individual participant data (IPD) meta-analysis

Background: There is accumulating evidence that digital breast tomosynthesis, referred to as 3D-mammography in this protocol, improves screen-detection measures compared to standard 2D-mammography in the context of population screening for breast cancer. However, the effect of 3D-mammography at follow-up of screened women is not yet known: it is unknown whether additional cancer detection from 3D-mammography leads to incremental screening benefit through a reduction of interval cancers, or whether it is mostly over-detecting indolent cancers. Methods: The aim of this study is to examine whether 3D-mammography population screening improves breast cancer screening effectiveness by reducing interval cancer rates compared to standard digital (2D) mammography screening, using individual participant data (IPD) meta-analysis. In this protocol, we outline the research plan which includes systematic identification of studies eligible to contribute data into the IPD meta-analysis, and sourcing and assembling IPD for participants screened with 3D-mammography (3D alone or integrated 2D/3D or integrated 2Dsynthetic/3D) and comparison participants screened with 2D-mammography (standard of care in breast screening). The primary end-point of this work is the interval breast cancer rate per 10,000 screens for 3D-mammography versus 2D-mammography screening. The IPD meta-analysis will also assess secondary outcomes including: screening sensitivity, cancer detection rates, cancer (prognostic) characteristics, and recall rates, for 3D-mammography versus 2D-mammography screening. The use of IPD meta-analysis will allow stratification of results by age and breast density, and will also facilitate analysis of cancer histological (prognostic) characteristics. Discussion: Finalization of data collection procedures and analysis plans will be complete by the end of 2017. Data collection will occur from late 2017 to late 2018 (screen-detection measures: cancer detection and recall data) and from mid-2018 to mid-2019 (interval cancer data). Results of detection measures should be available by 2019, and interval cancer results in 2020. By addressing the critical evidence gap on whether 3D-mammography screening reduces interval cancer rates (compared to 2D-mammography), we expect that our findings will inform timely translation of 3D-mammography technology into breast screening practice in population-based health programs.