Breast Cancer
Conditions
Keywords
breast cancer screening, extremely dense breasts, early detection, contrast-enhanced mammography, abbreviated MRI
Brief summary
Women with extremely dense breasts (nearly all glandular and connective tissue, little fatty tissue) have a 3-6 times higher risk of breast cancer than women with very low breast density. Moreover, due to the masking effect of the dense tissue, any breast tumours present are more difficult to detect in these women. With the results of the DENSE trial, the investigators showed that among women with extremely dense breasts, a combination of MRI and mammography could detect tumours earlier than mammography only. As the implementation of MRI in the screening program induces considerable costs and capacity requirements, the Dutch Ministry of Health would like to investigate whether cheaper and acceptable alternatives can be implemented more easily. In the DENSE-2 study, proposed here, we will investigate contrast-enhanced mammography and an abbreviated form of MRI as alternatives, in a large-scale randomized trial, within the current population-based screening program.
Detailed description
Women with extremely dense breast tissue have a higher risk of developing breast cancer and at the same time, mammography has limited value for these women. Currently, these women are not offered supplemental screening. Therefore, the investigators of the DENSE-2 trial will study supplemental CEM and AB-MRI screening in women with extremely dense breast tissue within the population-based breast cancer screening program because these modalities are expected to have higher diagnostic accuracy than tomosynthesis and ultrasound. In addition, these modalities are expected to be less expensive and require less capacity than a full MRI protocol as examined in the DENSE trial. For both CEM and AB-MRI, no results are currently available from a prospective screening study. The DENSE-2 trial is a randomized controlled trial comparing two intervention arms (CEM \[intervention arm A\] and abbreviated MRI \[intervention arm B\]) each with mammography \[control arm C\].
Interventions
DIAGNOSTIC_TESTContrast-enhanced mammography (CEM)
This intervention group receives supplemental screening with CEM after a negative screening result within the Dutch National Breast Cancer Screening program
DIAGNOSTIC_TESTAbbreviated MRI (AB-MRI)
This intervention group receives supplemental screening with AB-MRI after a negative screening result within the Dutch National Breast Cancer Screening program
Sponsors
C.H. van Gils
University Medical Center Groningen
Ziekenhuisgroep Twente
Radboud University Medical Center
Rijnstate Hospital
Zuyderland Medical Centre
Maastricht University Medical Center
Elisabeth-TweeSteden Ziekenhuis
Catharina Ziekenhuis Eindhoven
Jeroen Bosch Hospital
Erasmus Medical Center
Albert Schweitzer Hospital
St. Antonius Hospital
Antoni van Leeuwenhoek Hospital
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Bevolkingsonderzoek Nederland
Borstkankervereniging Nederland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
49 Years to 72 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant in the Dutch population-based breast cancer screening program with a negative mammography result (BI-RADS classification 1 or 2). * Extremely dense breast tissue (assessed with Quantra software, category D). * Age between 49-72 years (women are invited to the Dutch screening program in the year they turn 50, so the minimum age is 49 years. The maximum age for inclusion is 72 years to ensure that women can still participate in a second round of supplemental screening). * Living in the service area (travel distance of up to 60 km) of the 15 participating hospitals. * Absence of breast implants (Quantra cannot provide an accurate density determination for breasts with implants). * No objection to data sharing. * Not a participant in the DENSE trial or STREAM trial (participants in the DENSE and STREAM trials are known to the Dutch screening organization).
Exclusion criteria
The additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Interval Cancer Rate | 0 - 3 year | Measured as a breast cancer diagnosed in between two screening rounds |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Advanced Cancer detectio Advanced Cancer rate | 0 - 3 year | Advanced cancer is defined as TNM stage II or higher |
| Cancer detection rate | 0 - 3 year | The number of breast cancers detected by CEM or AB-MRI |
| False positive rate | 0-5 year | The number with a false positive result after CEM or AB-MRI |
| Participant experience with CEM - 1 | 0-5 year | screen-specific item questionnaire (SSI) |
| Participant experience with CEM - 2 | 0-5 year | Self-developed questionnaire |
| Participant experience with CEM - 3 | 0-5 year | Focus group interviews |
| Participant experience with AB-MRI - 1 | 0-5 year | screen-specific item questionnaire (SSI) |
| Participant experience with AB-MRI - 2 | 0-5 year | Self-developed questionnaire |
| Participant experience with AB-MRI - 3 | 0-5 year | Focus group interviews |
| Health-professional experience with CEM | 0-5 year | Self-developed questionnaire |
| Health-professional experience with AB-MRI | 0-5 year | Self-developed questionnaire |
| Estimated rate of overdiagnosis | 0-5 years | Simulation with the MISCAN software |
| Cost-effectiveness | 0-5 year | Simulation with the MISCAN software |
| Breast tumor size | 0-5 years | mm |
| Breast tumor stage | 0-5 years | TNM classification |
| Positive Predictive Value (PPV) | 0-5 year | Using the histological diagnosis as the reference test |
| Biopsy rate | 0-5 year | Per 1000 women screened with one of the modalities |
| Referral rate | 0-5 years | Per 1000 women screened per screening modality |
| Mortality rate | 0-5 year | Simulation with MISCAN software |
Countries
Netherlands
Contacts
CONTACTCarla van Gils, Prof
CONTACTEvelyn Monninkhof, Dr.
PRINCIPAL_INVESTIGATORCarla van Gils, Prof.
UMC Utrecht
Outcome results
None listed