Clinical trial NCT06636370: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer screening
extremely dense breasts
early detection
contrast-enhanced mammography
abbreviated MRI
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: University Medical Center Groningen
name: Ziekenhuisgroep Twente
name: Radboud University Medical Center
name: Rijnstate Hospital
name: Zuyderland Medical Centre
name: Maastricht University Medical Center
name: Elisabeth-TweeSteden Ziekenhuis
name: Catharina Ziekenhuis Eindhoven
name: Jeroen Bosch Hospital
name: Erasmus Medical Center
name: Albert Schweitzer Hospital
name: St. Antonius Hospital
name: Antoni van Leeuwenhoek Hospital
name: Amsterdam University Medical Centre, VUmc Site
name: Bevolkingsonderzoek Nederland
name: Borstkankervereniging Nederland
First posted: 2024-10-10
Enrollment: 36000
Sex: FEMALE
Minimum age (years): 49
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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 \[control arm C\].

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).

Primary outcomes:
measure: Interval Cancer Rate
timeFrame: 0 - 3 year
Secondary outcomes:
measure: Cancer detection rate
timeFrame: 0 - 3 year
measure: False positive rate
timeFrame: 0-5 year
measure: Participant experience with CEM - 1
timeFrame: 0-5 year
measure: Participant experience with CEM - 2
timeFrame: 0-5 year
measure: Participant experience with CEM - 3
timeFrame: 0-5 year
measure: Participant experience with AB-MRI - 1
timeFrame: 0-5 year
measure: Participant experience with AB-MRI - 2
timeFrame: 0-5 year
measure: Participant experience with AB-MRI - 3
timeFrame: 0-5 year
measure: Health-professional experience with CEM
timeFrame: 0-5 year
measure: Health-professional experience with AB-MRI
timeFrame: 0-5 year
measure: Estimated rate of overdiagnosis
timeFrame: 0-5 years
measure: Cost-effectiveness
timeFrame: 0-5 year
measure: Breast tumor size
timeFrame: 0-5 years
measure: Breast tumor stage
timeFrame: 0-5 years
measure: Positive Predictive Value (PPV)
timeFrame: 0-5 year
measure: Biopsy rate
timeFrame: 0-5 year
measure: Referral rate
timeFrame: 0-5 years
measure: Mortality rate
timeFrame: 0-5 year
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: Carla van Gils, Prof.
role: PRINCIPAL_INVESTIGATOR
References: