Supplemental Screening for Women With Extremely Dense Breast Tissue: the DENSE-2 Trial

Official title

Contrast-enhanced Mammography and Abbreviated MRI as Supplemental Screening Modalities for Women Aged 50-75 With Extremely Dense Breast Tissue: the DENSE-2 Trial

Overview

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 test Contrast-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 test Abbreviated 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

Primary outcome measures

• Interval Cancer Rate [Time frame: 0 - 3 year]

Secondary outcome measures (12)

• Advanced Cancer detectio Advanced Cancer rate [Time frame: 0 - 3 year]
• Cancer detection rate [Time frame: 0 - 3 year]
• False positive rate [Time frame: 0-5 year]
• Participant experience with CEM - 1 [Time frame: 0-5 year]
• Participant experience with CEM - 2 [Time frame: 0-5 year]
• Participant experience with CEM - 3 [Time frame: 0-5 year]
• Participant experience with AB-MRI - 1 [Time frame: 0-5 year]
• Participant experience with AB-MRI - 2 [Time frame: 0-5 year]
• Participant experience with AB-MRI - 3 [Time frame: 0-5 year]
• Health-professional experience with CEM [Time frame: 0-5 year]
• Health-professional experience with AB-MRI [Time frame: 0-5 year]
• Estimated rate of overdiagnosis [Time frame: 0-5 years]

Eligibility criteria

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 exclusion criteria for the intervention arms are checked after randomization and recruitment (this order is due to the pre-randomization design):

• Presence of in-body metals (only for AB-MRI, this involves specific metals and is asked by telephone).
• Previous allergic reaction to the provided contrast agent.
• Renal insufficiency (glomerular filtration rate <30 ml/min) (only for CEM, is checked for with questionnaire I and possibly renal function measurement).
• Severe claustrophobia (only for AB-MRI).
• Severe obesity (weight >150 kg) (only for AB-MRI).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Screening

Study locations

Netherlands · 1 center

• UMC Utrecht — Utrecht

Identifiers

NCT: NCT06636370 · 05550412310002 · Nr. 2024/09

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗