Project Funding Details

In the Netherlands, breast cancer screening is performed with digital mammography (DM), a two-dimensional (2D) imaging modality. Imaging the breast with a 2D modality requires collapsing all information into a single plane, so tissues separated only in the perpendicular direction appear in the same location in the mammogram. This results in about 25% of cancers being diagnosed as interval cancers, i.e., cancers that are not detected at screening but only within two years after screening (1). Furthermore, tissue superposition also results in false positive recalls for further assessment. Digital breast tomosynthesis (DBT) is a new imaging modality similar to DM that reduces the problem of tissue superposition (2,3). DBT involves acquiring various low-dose mammograms over a limited angle. These are then processed to construct a pseudo-3D stack of slices, each separated vertically by 1 mm. In the last decade, several large-scale European studies have shown that DBT improves the short-term outcomes for detection of breast cancer compared to mammography. DBT increases the detection rate from ~6 to ~9 cancers per 1000 women screened, while the recall rate approaches 3.5% to 4%, independent of the initial recall rate (4–8). Since its recall rate is only 2.4%, introducing DBT in the Dutch screening setting will likely generate an increase in false positives. However, the impact of DBT screening on medium-term outcomes, in terms of reduction of interval cancers and of detection of advanced cancers, is not yet clear. Although the prospective screening trials mentioned above were considerable in size, they were powered to detect changes in cancer detection and recall rates, not in interval cancers or advanced cancers. As a result, the real impact on the latter outcomes is unknown, with up to now only disparate results being available (9–13). Furthermore, the ~50x increase in the number of images resulting from a DBT exam compared to a DM exam doubles the reading time. For DBT screening in the Netherlands to be feasible from the economic and human resources point of view, the interpretation of these cases must be accelerated, to result in an average reading time comparable to that of reviewing DM exams. Given all these uncertainties, it is currently impossible to determine what would be the long-term effects of transitioning to DBT screening in the Netherlands, in terms of reduction in breast cancer mortality and morbidity, and in cost-effectiveness. To determine these effects, advanced modelling is needed, which requires accurate estimation of the short- and medium-term outcomes of DBT screening, as well as an understanding of the costs of DBT screening, including acquisition and image interpretation costs. The aim of this project, therefore, is to determine the short-, medium-, and long-term outcomes of nationwide DBT breast cancer screening in the Netherlands, when an optimal image acquisition and interpretation strategy is used. The screening program has already replaced its entire screening DM imaging infrastructure for a new, DBT-capable, one. DBT, however, will not be used until the above-mentioned issues are addressed and any unforeseen challenges resolved. In this project we aim to tackle these remaining issues so that the benefits of DBT, if these exist, can be brought to the entire Dutch population of screened women. Work Package (WP) 1 will involve the introduction of DBT in 5 of the 71 screening units in the country, to screen 18,200 women for two screening rounds, and compare their results to those of another 86,400 women undergoing standard DM screening. This will allow us to identify the impact of this transition on the screen-detected cancer and recall rates, and on interval and advanced cancer rates, as well as any barriers for acceptance of DBT screening. During screening, the attendees, screening radiographers, and radiologists will be surveyed to identify any barriers that limit acceptability of this new modality. By including a second, incidence DBT round, we will be able to determine the real performance of DBT screening in the Netherlands, since subsequent screening makes up about 90% of the program. Most importantly, this study is powered to detect a combined one-third reduction in the interval and advanced cancer rates with DBT screening. In Work Package 2, we will identify the optimal DBT acquisition and reading strategy to be used in the Dutch DBT screening program so as to minimize the increase in reading time with DBT. For this, we will perform retrospective observer studies, using the images from WP1, to test eight different acquisition and reading strategies, some involving the use of cutting-edge artificial intelligence computer systems, for DBT-based screening. These strategies have been shown in initial studies, many performed by us, to result in a significant reduction in reading time, with no or minimal loss in performance. Once the optimal combination of acquisition and reading strategies is identified, to determine its actual real-world performance and impact on reading time, it will be used to interpret the entire second round of DBT screening acquired in WP1 at the screening reading units. Finally, in Work Package 3, we will use the results from the other two WPs to model the entire DBT screening program and therefore predict the long-term outcomes and cost-effectiveness of this new screening program. The only method possible to estimate the impact of screening on long term effects such as breast cancer mortality and morbidity, as well as cost-effectiveness, is the use of modelling. Therefore, we will use the well-validated MISCAN model with the data and results gathered, to estimate the long-term impact of DBT screening. As a result of this project, we will have shown if breast cancer screening with DBT in the Netherlands should be implemented or not. We will also show, were it to be introduced, how it should be implemented, having addressed all the remaining questions, and having found the optimal DBT workflow specifically for a high-volume population-based screening program. The latter means that this project will not only have high impact on breast cancer screening in the Netherlands, but its outcomes will also extend to a large proportion of the European population.  

Achtergrond en probleemstelling In Nederland krijgen alle vrouwen in de leeftijd van 50 tot 75 jaar elke twee jaar een screeningsonderzoek aangeboden om een eventueel aanwezige borstkanker zo vroeg mogelijk op te sporen en te behandelen. Hoewel er met enige regelmaat discussie is over het nut van screening op borstkanker, staat het Nederlandse bevolkingsonderzoek bekend als een gebalanceerde gezondheidszorgvoorziening waarvan de voordelen opwegen tegen de nadelen. Het screeningsonderzoek bestaat uit twee digitale röntgenfoto’s van elke borst. Deze foto’s geven een tweedimensionaal beeld van de borst. Dit heeft als nadeel dat structuren in de borst over elkaar heen geprojecteerd worden waarmee het lijkt dat er een afwijking aanwezig is of deze juist over het hoofd gezien wordt. Dit kan ertoe leiden dat vrouwen verwezen worden naar het ziekenhuis voor nader onderzoek, waarbij geen borstkanker gevonden wordt, of dat een borstkanker gemist wordt. Onderzoeksrichting/voorgestelde oplossing Digitale tomosynthese is een röntgentechniek waarmee een driedimensionaal beeld van de borst gemaakt wordt. Van een gemiddelde borst, 5 tot 6 cm dik, worden zo’n 50 opnamen met een lage stralingsdosis gemaakt, elk van ongeveer 1 mm dik. Deze plaatjes komen samen in een driedimensionaal beeld waardoor structuren niet overlappen en de screeningsradioloog meer informatie over een mogelijke afwijking heeft. Europese studies in screeningsprogramma’s hebben laten zien dat tomosynthese meer borstkankers op kan sporen dan digitale mammografie. Tomosynthese verhoogt de detectie van 6 naar 9 borstkankers per 1000 gescreende vrouwen, bij een verwijscijfer tussen de 3,5 en 4%. Aangezien Nederland een laag verwijscijfer heeft met digitale mammografie (2,4%), zal het aantal verwijzingen, en daarmee het aantal fout-positieve uitkomsten, mogelijk toenemen. Nog niet duidelijk is of de extra gevonden borstkankers leiden tot gezondheidswinst en een lager aantal borstkankers dat tussen screeningsronden in (intervalkankers) of in een gevorderd stadium gediagnosticeerd wordt.  Relevantie In dit project onderzoeken we of tomosynthese door het eerder opsporen van borstkanker de borstkankersterfte verder kan verlagen en de kwaliteit van leven voor vrouwen met borstkanker kan verbeteren. Door de introductie van deze nieuwe techniek kunnen we de voor- en nadelen van het bevolkingsonderzoek borstkanker mogelijk nog beter in balans brengen. Aangezien bijna een miljoen vrouwen per jaar deelnemen aan het bevolkingsonderzoek draagt dit bij aan vermindering van de ziektelast door borstkanker en daarmee aan de volksgezondheid in Nederland.

---

Cancer Types

• Breast Cancer

---

Common Scientific Outline (CSO) Research Areas

• 4.3 Early Detection, Diagnosis, and Prognosis Technology and/or Marker Testing in a Clinical Setting