Effectiveness of hybrid digital breast tomosynthesis/digital mammography compared to digital mammography in women presenting for routine screening at Maroondah BreastScreen: Study protocol for a co-designed, non-randomised prospective trial

Abstract

Background

Digital breast tomosynthesis (DBT) for breast cancer screening has been shown in international trials to increase cancer detection compared with mammography; however, results have varied across screening settings, and currently there is limited and conflicting evidence on interval cancer rates (a surrogate for screening effectiveness). Australian pilot data also indicated substantially longer screen-reading time for DBT posing a barrier for adoption. There is a critical need for evidence on DBT to inform its role in Australia, including evaluation of potentially more feasible models of implementation, and quantification of screening outcomes by breast density which has global relevance.

Methods

This study is a prospective trial embedded in population-based Australian screening services (Maroondah BreastScreen, Eastern Health, Victoria) comparing hybrid screening comprising DBT (mediolateral oblique view) and digital mammography (cranio-caudal view) with standard mammography screening in a concurrent group attending another screening site. All eligible women aged ≥40 years attending the Maroondah service for routine screening will be enrolled (unless they do not provide verbal consent and opt-out of hybrid screening; are unable to provide consent; or where a ‘pushback’ image on hybrid DBT cannot be obtained). Each arm will enrol 20,000 women. The primary outcomes are cancer detection rate (per 1000 screens) and recall rate (percentage). Secondary outcomes include ‘opt-out’ rate; cohort characteristics; cancer characteristics; assessment outcomes; screen-reading time; and interval cancer rate at 24-month follow-up. Automated volumetric breast density will be measured to allow stratification of outcomes by mammographic density. Stratification by age and screening round will also be undertaken. An interim analysis will be undertaken after the first 5000 screens in the intervention group.

Discussion

This is the first Australian prospective trial comparing hybrid DBT/mammography with standard mammography screening that is powered to show differences in cancer detection. Findings will inform future implementation of DBT in screening programs world-wide and provide evidence on whether DBT should be adopted in the broader BreastScreen program in Australia or in subgroups of screening participants.

Trial registration

The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR, ACTRN12623001144606, https://www.anzctr.org.au/). Registration will be updated to reflect trial progress and protocol amendments.

Highlights

• •Trials of DBT have varied across settings with limited evidence on interval cancer rates.
• •Substantially longer screen-reading time for DBT poses a barrier for adoption.
• •Hybrid DBT/DM will be evaluated to address reading time in this Australian trial.
• •20,000 women per arm will be enrolled at two sites: hybrid DBT/DM vs mammography.
• •Cancer detection, recall, reading time, and interval cancer rates will be reported.

1. Background

Breast cancer is the most common cancer in women. Randomised trials have shown that mammography screening confers benefit through early detection leading to reduced breast cancer mortality; however, there are also harms such as false-positive results [1,2]. In Australia, the national population-based screening program (BreastScreen Australia) uses standard two-view per breast digital mammography (DM or 2D-mammography). Evidence on a new mammography technology, digital breast tomosynthesis (DBT or 3D-mammography), for population breast screening has accumulated over the past decade [[3], [4], [5], [6], [7], [8]]. Prospective trials [3,5,[7], [8], [9], [10]] and retrospective evaluations [4,[11], [12], [13], [14], [15]] have shown that using tomosynthesis with (or instead of) standard mammography improves screening detection measures compared to mammography alone but there is variability in results across screening settings [16,17]. Three randomised trials [[18], [19], [20]] from European programs have reported in more recent years that DBT increased cancer detection rates relative to mammography, and another RCT from Norway showed a reduction in recall but no increased cancer detection from DBT [21]. At longer follow-up of screened women, there is limited and conflicting evidence on differences in interval cancer rate (cancers not detected at screening) for DBT vs mammography [18,22,23].

Internationally, many organised screening programs recommend DM for screening but support investigation of DBT in a research context or allow conditional use of DBT. European guidelines conditionally recommend DBT as an option for screening women of average risk and women with high breast density based on low certainty evidence [24], while the integration of DBT into population screening has been recommended in France [25]. In Australia, DBT has been progressively integrated into private radiology practice and some public radiology services for diagnosis and early detection of breast cancer. DBT is also used in most BreastScreen Australia services for assessment of screen-detected findings where it provides additional diagnostic information. However, DBT is not used for routine screening in the BreastScreen Australia program because it is unclear whether the enhanced cancer detection observed in international studies will transfer to the Australian setting. Importantly, it is unknown whether the additional cancer detection will improve longer term outcomes (for example whether it further reduces breast cancer mortality) compared to DM screening.

Given the growing adoption and evaluation of DBT [17] and heterogeneity in detection measures across screening settings [16,17], a pilot trial was undertaken in Australia's BreastScreen Victoria program to assess initial detection metrics and to determine the feasibility of DBT screening [26]. The pilot study showed that DBT increased cancer detection (DBT 9.8/1000 screens, DM 6.6/1000 screens), as well as recall rates (DBT 4.2%, DM 3.0%) [26,27]. It also reported a longer screen-reading time for DBT, highlighting logistical problems for resourcing DBT screen-reading and the need for new trials examining a more feasible screen-reading strategy (for example, limited DBT views [28]) to support implementation, and the potential for DBT reading times to reduce with experience as shown in a trial from BreastScreen Norway [29].

Findings from the Australian pilot study highlight the need to obtain additional evidence from the BreastScreen Australia program setting to inform the future role of DBT in Australian screening practice, and using a potentially more feasible DBT screen-reading approach that both addresses the longer screen-reading time and minimises the additional radiation exposure associated with DBT [26]. We therefore propose hybrid DBT/DM screening, incorporating the mediolateral oblique (MLO) view from DBT (with synthetic 2D from DBT acquisition) and the craniocaudal (CC) view from DM, to facilitate implementation, scale-up, and to inform other programs considering DBT screening. In addition, a meta-analysis of international studies found differential detection by breast density for DBT, highlighting the need for stratification of outcomes by density [16]. Therefore, a larger trial is planned to provide evidence to address these persistent evidence gaps, including quantifying density-stratified screening outcomes from the Australian BreastScreen program context.

2. Methods/design

2.1. Objectives

The primary objective of this study is to examine the effectiveness of hybrid DBT/DM screening (the intervention) compared to standard DM screening, in women presenting for routine breast screening at Maroondah BreastScreen, Eastern Health. Effectiveness will assess initial screen-detection outcomes (cancer detection rates, recall rates), and will be reported in the overall groups as well as stratified by breast density.

The study will address the following secondary objectives:

• •Measure and describe screen-reading time for hybrid digital DBT/DM screening (intervention) compared to standard DM screening.
• •Describe (and compare) the characteristics of detected breast cancers (size, histology, grade, node status, and biomarkers) in each group.
• •Report ‘opt-out’ rate as a proxy for acceptability of the intervention.
• •Describe the assessment outcomes for recalled women in each group.

The study will also address the following secondary objectives at longer follow-up:

• •Estimate and compare interval cancer rates (ascertained at 2-year follow-up) for both the intervention group and the comparison group (overall, and stratified by density) using established BreastScreen processes that routinely obtain these data (via linkage to the Victorian Cancer Registry).

2.2. Trial design

This study is a prospective trial embedded in population-based BreastScreen Australia services, comparing the intervention screening (hybrid DBT/DM) with standard DM screening in a concurrent group attending another screening site (both services are part of Maroondah BreastScreen at Eastern Health, Victoria). Fig. 1 shows the design of the study. Table 1 reports the schedule of enrolments, interventions and assessments. The study protocol has been developed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidance [30] (Appendix 1).

Fig. 1.

Schema of a co-designed trial of hybrid DBT*/mammography population screening (SPIRIT diagram).

*Digital breast tomosynthesis (MLO) acquisition from which synthesized 2D-images are also reconstructed. ǂMD: mammographic density (Volpara automated density measure).

Table 1.

Patient assessment schedule.

Study period
Timepoint	Enrolment	Screening examination	Assessment (recalled women)	Follow-up (24 months)	Closeout
	0	t1	t2	t3	tx
Enrolment:
Invitation to screen	X
Informed consent (hybrid DBT/DM group)	X
Interventions:
Hybrid DBT/DM		X
DM		X
Assessments:
Opt out	X
Baseline characteristics		X
Automated volumetric breast density		X
Screen-reading time		X
Radiation metrics		X
Number of recalls		X
Number and type of testing procedures			X
Number of cancers detected			X
Cancer characteristics			X
Number of interval cancers				X

2.3. Study setting

Maroondah BreastScreen, Eastern Health provides screening services at the two study sites. Women participating in breast screening through the Maroondah service (East Ringwood site), will be invited into the study for the intervention screening. Women presenting for screening at the other site (Mont Albert) will form a concurrent comparison group and will have standard DM screening.

2.4. Study endpoints

The primary endpoints are cancer detection rate (number of cancers detected per 1000 screens), recall rate (percentage of recalls to assessment), and false-positive recall (the number of recalled women shown not to have cancer at assessment as a proportion of the total screened, minus those shown to have cancer).

Secondary outcome measures include:

• •Participation (or ‘opt-out’) rates for the trial: the number of women who accepted participation (or opted out of study) from the number invited (simple proportions).
• •Descriptive data for cohort characteristics (routine demographics at baseline; breast density categories).
• •Descriptive data on the characteristics of breast cancers (size, histology, grade, node status, and biomarkers) detected in the study participants.
• •Descriptive data on assessment testing and outcomes: number and type of assessment procedures (including biopsy); assessment outcomes or recommendations.
• •Quantitative measures of screen-reading time: the time taken to report each screening examination will be measured per screen-reader and the average screen-reading time will be estimated.
• •Number of interval cancers (which is reported routinely in the BreastScreen program via linkage to the Victorian Cancer Registry) at 24 months from screening, to allow estimation of interval cancer rates and screening sensitivity, i.e. number of screen-detected cancers as a proportion of total number of cancers (screen detected + interval cancers).

2.5. Inclusion criteria

BreastScreen targets women aged 50–74 years, but allows women aged 40–49 years and over the age of 74 years to participate in screening. All women attending Maroondah BreastScreen (East Ringwood service) aged ≥40 years will receive hybrid DBT/DM (unless they ‘opt-out’). An information sheet about the trial (Appendix 2) will be provided to women as part of the pre-attendance ‘information package’ already given to women who book a screening appointment. Women who decline participation in the trial will have standard DM. Women attending the second screening site (Mont Albert service) will have standard DM and will be included in the comparison group.

2.6. Exclusion criteria

Women deemed unable to provide consent to having mammography screening will be ineligible to take part in the study. Women with disabilities who are unable to provide verbal consent for hybrid DBT/DM screening will have standard DM. Women with breast implants where a ‘pushback’ image can be obtained (an image of the glandular tissue in front of the implant) can be included however women where a ‘pushback’ image cannot be obtained will be excluded from having hybrid DBT/DM and will have DM.

2.7. Informed consent process

The study will obtain individual written informed consent using the standardised BreastScreen Victoria registration form (Appendix 3). This form provides consent for screening mammography and the use of screening participants' data for the purpose of research [31]. Women who respond to invitation by BreastScreen Victoria to participate in screening are routinely sent an information pack including information relevant to consent and to screening procedures, and the booking details for the screening visit. An additional 1-page information sheet about the study will be included in the information pack sent to those attending Maroondah BreastScreen (East Ringwood site) during the recruitment phase of the study (Appendix 2). Screening participants will have the option to verbally consent or to opt-out of the study and receive standard DM screening if they do not want to take part in the trial. The radiographers will confirm the participants' consent in the screening room before commencing the mammogram.

2.8. Mammography technology and screen-reading

MLO and CC views of each breast will be obtained. The intervention screen comprises DBT acquisition for the MLO view (2D-images will be reconstructed from the DBT data: synthetic 2D or C-view) plus standard DM acquisition for the CC view. The proposed technologies (Selenia® Dimensions and 3Dimension Units with C-View™ 2D-software) have been in use at Maroondah BreastScreen since 2013 for the diagnostic assessment of screen-detected abnormalities. Standard 2D DM in the comparison group will be performed with Siemens Mammomat Inspiration. Although different DM units are used at the intervention and control sites, this practical limitation in methodology is not expected to confound any differences in detection outcomes observed between the groups [32] although it limits comparative radiation dosimetry.

Given the relevance of mammographic breast density for screening programs and our findings from the pilot trial that DBT has differential detection and recall by density, automated volumetric breast density will be measured to allow reporting of screening outcomes stratified by mammographic density. This will be performed for both the intervention group and the comparison group. Automated breast density software (Volpara Health) will be used to measure density (this uses the raw data from the acquired views: both DM views in the control arm, and CC from DM and MLO from DBT in the intervention arm).

All other aspects of screening, screen-reading and assessment, and any required follow-up, will be based on standard Maroondah BreastScreen protocols and, where applicable, Eastern Health protocols. The standard BreastScreen Australia National Accreditation Standard of double-reading practice (two independent readings to interpret each screen) will be followed and any disagreement between readers will use a third reader to arbitrate as currently practiced at Maroondah BreastScreen.

2.9. Sample size

The primary outcome for this study is cancer detection rate (CDR) per 1000 screens. Assuming a CDR of 6.6/1000 screens for mammography and a CDR of 9.1/1000 screens for DBT (hence a CDR difference 2.5/1000) [26,27], a minimum of 19,561 screenings are required in each group to detect this difference with 80% power. This estimated CDR difference is slightly lower than that quantified in the pilot study [26] to allow for use of the hybrid intervention and around 10% repeat screens in the timeframe of the trial. Allowing for around 1% incomplete assessments or data, we plan to recruit 20,000 women per group.

2.10. Recruitment

Given a volume of 9400–10,000 screening exams per year for each screening service and allowing for 5% opt-out rate for the intervention group (based on the pilot trial), active recruitment is anticipated to require around 28 months. Interval cancer data will be provided after an additional 2 years of follow-up, resulting in a total study duration of approximately 52 months. Recruitment is expected to commence in March 2024, and will continue until the sample size is met.

2.11. Blinding

It is not possible to blind participants, technologists or screen-readers in this study.

2.12. Data collection and management

Collection of data at the screening episode and the results of the screen, and all recall and assessment results, are routinely undertaken at BreastScreen Victoria. The handling of data at Maroondah BreastScreen (and generally in BreastScreen Victoria) is undertaken by dedicated data and administration staff who routinely handle and enter all data as part of the woman's care at BreastScreen and for quality assurance. The standard BreastScreen Victoria consent form allows the collection of such data for the purpose of clinical care and program quality assurance, for monitoring screening outcomes, and for use in research (Appendix 3). Screening participants' details are recorded on BreastScreen Victoria's information system, and images are archived on the state-wide Picture Archiving and Communications System (PACS). The information system and the PACS system are both password protected: access to information in both these systems is login-specific and task-specific allowing access to users defined by their specific roles and need to access information for each screening episode. The research team will not have access to these systems, except where that is part of the individual's work duties at BreastScreen. Maroondah BreastScreen staff are routinely required to sign and comply with the service's confidentiality agreement as well as Eastern Health's relevant policies and BreastScreen Australia National Accreditation Standards around confidentiality.

Data variables obtained for the study will be consistent with data routinely collected or obtained as part of the screening, assessment (for recalled cases) and outcomes ascertainment processes of the BreastScreen program, except where specifically warranted for pre-specified study measures (screen-reading time; breast density). Data variables will include (i) data on screening attendance (such as date of screen; first or repeat screen), age, ethnicity, history (such as personal history of breast cancer), and current report of breast symptoms, if any; (ii) data acquired as part of the screening and imaging process (radiation data; technical repeats) and the screen-reading process (interpretive time; frequency of discordant reads); (iii) screening results, assessment work-up and results for recalled women (additional testing; results of testing; biopsy; surgery recommendations and surgery outcomes/treatment); data from histopathology reports (core needle biopsy, and excision biopsy results); and cancer features. Interval cancer data (at 2-year follow-up) will be obtained from established BreastScreen processes which include linkage to the Victorian Cancer Registry to ascertain interval cancers and report interval cancer rates as part of screening quality assurance. Mammographic breast density will be measured in the study to allow reporting by breast density strata, as this represents key evidence to inform decisions on the accuracy and utility of DBT in screening.

Study databases will be assembled by BreastScreen Victoria for the trial and will be provided to the research team (a) after 5000 screens as part of a monitoring process of the intervention group; (b) after completion of recruitment (allowing time for collection of outcomes data following assessment); and (c) at 2-year follow-up to obtain interval cancer data. Study databases will be password protected and transferred using secure processes and will only be accessible to essential designated research investigators.

2.13. Adverse events record and safety assessment

Discomfort from breast compression, the only relatively common adverse experience from mammography, is transient and limited to the time that the breast is compressed or within a short period following compression. Skin bruising attributed to compression from the mammogram is rare and is generally noted after the woman's screening visit is completed. Given the mild and transient nature of the above-described adverse events, there is no formal BreastScreen mechanism to evaluate and record these events. Furthermore, they are no more likely to occur using DBT compared to standard mammography, and therefore will not be specifically evaluated for the study.

Serious adverse events are not anticipated for mammography screening, but if any should occur they will be reported in line with the National Health and Medical Research Council (NHMRC) National Statement on Ethical Conduct in Human Research [33]. Specifically, these will be reported to the trial's Committee, to BreastScreen Victoria, and will also be notified to the Eastern Health Human Research and Ethics Committee (HREC) and Victoria Health Incident Management System (Riskman).

2.14. Statistical analysis

Primary endpoints of CDRs and proportions of recalls will be computed for each screening modality, with exact (Clopper–Pearson) 95% confidence intervals (CIs); differences between groups will be calculated with Miettinen–Nurminen 95% CIs. Groups will be compared with Fisher exact tests. Secondary outcomes will be compared with Fisher exact tests (proportions) or independent samples t-tests (continuous data).

Stratified analyses will be undertaken to report cancer detection rates and recall rates by breast density, categorised using BI-RADS density categories (A, B, C, D), and re-stratified as low density (BI-RADS A-B) versus high density (BI-RADS C-D). Additional subgroup analyses will report these outcomes by age-groups and screening round (first versus repeat) strata.

2.15. Interim analysis and monitoring

An interim analysis will be undertaken after the first 5000 DM/DBT screens to monitor the primary outcomes in the intervention group. Cancer detection and recall rates (with 95% CIs) will be calculated. Radiation metrics (mean glandular dose (mGy) per view and/or per screening examination will also be described. This preliminary monitoring report will feed back the findings to investigators and BreastScreen Victoria Research Advisory Committee. Interim analyses will not report comparisons to the standard DM screening group. For an expected DBT cancer detection rate of 9.1 per 1000 screens, an interim sample size of 5000 screens would yield a standard error of approximately 1.3 per 1000 screens. For recall rate of 4.2% (based on the pilot trial), this would result in a standard error of 0.28%.

Early termination of the study is unlikely, given the very low risk of adverse events, and given that participants are actively presenting for routine mammography screening and are simply having a modified form of mammography when they participate in the study. Early termination may be considered as a consensus decision by all investigators in the event that major technical difficulties emerge during implementation. This is highly unlikely based on Maroondah BreastScreen's experience of using DBT imaging and given the successful completion of the pilot study [26].

All BreastScreen services routinely monitor and report screening data according to the BreastScreen Australia National Accreditation Standards, relating to screening detection measures: this study will implement the same monitoring and reporting for DBT as per the current DM reporting requirements. Based on the very low risk to participants and with reference to the guidance provided by NHMRC on research monitoring to be commensurate with risk to participants [33], an Independent Data Monitoring Committee will not be established.

2.16. Ethical approval and trial registration

The trial has been approved by the Eastern Health HREC (LR23-059-102540) and is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR, ACTRN12623001144606, https://www.anzctr.org.au/). Registration will be updated to reflect trial progress and protocol amendments, as required. Any deviations from the protocol will be formally notified to the Eastern Health HREC.

2.17. Patient and public involvement

A consumer representative (SV) advised on the study processes and reviewed the protocol, and will provide ongoing advice about language, including lay summaries; links between consumers, the community and the researchers, including dissemination of the findings to consumer groups.

2.18. Dissemination plans

Participant-level data generated by the current study are not publicly available due to data confidentiality agreements with data custodians. Results will be made publicly available at the summary level. Manuscripts reporting primary and secondary outcomes will be published in peer-reviewed journals and results will also be presented at relevant scientific meetings. Authorship will reflect International Committee of Medical Journal Editors guidelines. Findings from the trial will be reported to BreastScreen Victoria and BreastScreen Australia to support screening policy decisions. A ‘plain English summary’ will be prepared for the purpose of communicating study findings to the public, including women who attend BreastScreen.

3. Discussion

This research represents Australia's first prospective trial of DBT for population screening with sufficient power to show whether the technology significantly improves cancer detection measures. Building on pilot work on the feasibility of implementing DBT in Maroondah BreastScreen, the study will provide information that can inform whether this new technology, evaluated as hybrid DBT/DM acquisitions (one view of each), should be implemented in the broader BreastScreen Australia program, or whether it should be considered in subgroups of screening clients. The co-design of the study with the screening program ensures suitability of the intervention for screening services as well higher likelihood of adoption if supported by the findings of the trial.

Our earlier pilot trial highlighted substantially prolonged screen-reading time for DBT, limiting the potential for its implementation in Australian population screening [26,27]. Internationally, a prospective study in the Swedish national screening program evaluated alternative strategies for DBT screening by comparing standard two-view mammography screen-reading with DBT-MLO view screen-reading (standard CC was also available), where all acquisitions were from the same participants [10,28]. This paired design in the Swedish trial showed that the proportion of cancers detected was significantly higher with the DBT (MLO) than with standard mammography [28]. Our innovative trial will evaluate a modification of this approach by using a hybrid acquision (DBT/DM) with the potential to require shorter screen-reading time relative to DBT acquisition in both views, and additionally minimise overall radiation exposure for the screening examination. Hybrid DBT/DM therefore holds promise as a potentially more feasible model for implementation in BreastScreen Australia. Given the heterogeneity in screening outcomes for DBT between settings [17], the current trial will provide important information on the effectiveness of this hybrid approach in the Australian population screening context. This knowledge will also be relevant to screening programs in other countries contemplating DBT screening.

The reconstructed, quasi-3D images provided by DBT have the potential to better visualise cancers that may be obscured by dense breast tissue on DM [6]. Meta-analysis of studies comparing DBT (with or without DM) to standard DM have found greater incremental detection for DBT in women with high breast density, although the magnitude of this difference varied by setting [16]. Our Australian pilot trial also found significantly greater CDR and recall rates in women with dense breasts [27]. Considerations around density-tailored screening may therefore be relevant to implementation of DBT in population-based screening programs. By stratifying screening outcomes by density, our trial of hybrid DBT/DM will further inform potential models of implementation for DBT in BreastScreen Australia.

The adoption of DBT for population breast cancer screening varies between countries; while it has become widely used in some settings (for example, the USA), in other countries 2D mammography is used for screening although the evaluation of DBT is recommended [24]. Given that many screening programs use double-reading, resourcing these reads is a greater challenge if DBT is used instead of 2D mammography. We are exploring a hybrid DBT/DM imaging strategy in our trial, but alternate approaches could also be explored to implement DBT. With the evolution of artificial intelligence (AI) algorithms for automated interpretation of DM, and prospective trials reporting improvements in cancer detection with this technology [34], AI may play a role in addressing potential resourcing challenges associated with DBT in the future.

Availability of data and materials

The datasets generated and/or analysed during the current study are not publicly available due to data confidentiality agreements with data custodians.

Ethics approval and consent to participate

The study has been approved by the Eastern Health HREC (LR23-059-102540).

Sources of funding

This work is funded by a National Breast Cancer Foundation (NBCF) Endowed Chair Grant (EC-21-001; 2021-31), and co-funded by a National Health and Medical Research Council (NHMRC) Investigator, Leadership Grant (1194410; 2021-25), both awarded to NH.

CRediT authorship contribution statement

Nehmat Houssami: Writing – original draft, Methodology, Funding acquisition, Conceptualization. Darren Lockie: Writing – review & editing, Methodology. Michelle Giles: Writing – review & editing, Methodology. Sally Doncovio: Writing – review & editing, Methodology. Georgina Marr: Writing – review & editing, Methodology. David Taylor: Writing – review & editing, Methodology. Tong Li: Writing – review & editing, Methodology. Brooke Nickel: Writing – review & editing, Methodology. M Luke Marinovich: Writing – original draft, Methodology.

Declaration of competing interest

The authors declare that they have no competing interests.

Abbreviations

AI

artificial intelligence

ANZCTR

Australian New Zealand Clinical Trials Registry

CC

cranio-caudal

CDR

cancer detection rate

CI

confidence interval

DBT

digital breast tomosynthesis

DM

digital mammography

HREC

Human Research and Ethics Committee

MLO

mediolateral oblique

NHMRC

National Health and Medical Research Council

PACS

Picture Archiving and Communications System

Appendix A. Supplementary data

The following are the Supplementary data to this article: