Tomosynthesis as Primary Test for Breast Cancer Screening (MAITA)

Tomosynthesis as Primary Test for Breast Cancer Screening: A Multicenter Randomized Controlled Trial

Randomized trial comparing tomosynthesis plus synthetic 2D Mammography vs Digital Mammography in respect to incidence of advanced cancers (interval and following round) and interval cancers.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: tomosynthesis + synthetic 2D; Diagnostic test: digital mammography

Detailed Description

This is a companion study of the other Italian studies on tomosyntesis as primary screening test for breast cancer: RETomo (NCT02698202), PROTEUS (NCT02590315), IMPETO (NCT03587259). The investigators conduct a randomized trial in three centres with a protocol that is similar to that of the other three studies. As for IMPETO and differently from the RETomo and PROTEUS studies, the intervention will be tomosynthesis + synthetic 2D.

In the three centres about 8000 women will be recruited (4000 in the experimental arm and 4000 in the control arm).

The study will compare the performance of tomosynthesis plus synthetic 2D vs digital mammography in respect to incidence of advanced cancers (interval and following round) and interval cancers. Women 50 to 65 years old will be screened once according to randomization arm for one round, then all will be screened with digital mammography after two years.

The investigators also will measure detection rates, specificity, interval cancers, advanced cancers occurring as interval cancers or at subsequent screens and allowing to estimate excess overdiagnosis comparing overall cumulative incidence after two or three rounds of screening.

Women will be asked for informed consent when they attend the mammography. If they accept they will be randomised to one of the two arms.

All examinations will be read by two independent radiologists, in case of discordance a third reading is asked.

• Study Type: Interventional
• Enrollment (Actual): 10156
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy
    • IRCCS Policlinico San Donato
  • Reggio Emilia, Italy, 42122
    • Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia
  • Verona, Italy
    • Azienda Ospedaliera Universitaria integrata
  • Verona, Italy
    • Azienda ULSS 9 Scaligera

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women scheduled for a new round of mammographic screening
• resident in the province

Exclusion Criteria:

• previous breast cancer diagnosis
• pregnancy or suspicion of pregnancy
• presence of BRCA1/2 gene mutation
• Previous Digital Breast Tomosynthesis performed
• unable to understand informed consent
• chemotherapy in progress
• presence of breast implant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tomosynthesis + synthetic 2D; Women will be screened for one round with tomosynthesis + synthetic 2D, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings. After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.	Diagnostic test: tomosynthesis + synthetic 2D; Women will be screened for one round with tomosynthesis + synthetic 2D, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings. After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.
Active Comparator: Digital Mammography; Women will be screened for digital mammography, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings. After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.	Diagnostic test: digital mammography; Women will be screened for one round digital mammography, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings. After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
advanced cancer incidence	cumulative incidence of T2+ cancers after first screening round	2 years (+9 months to complete second round assessment)
advanced cancer incidence	cumulative incidence of T2+ cancers after first screening round	4 years (+9 months to complete third round assessment)
interval cancer incidence	incidence of cancers occurring after a negative screening test and before the next scheduled screening round. Outcome 3 and 4 will are combined in one single outcome.	2 years for 50-65 years old women
interval cancer incidence	incidence of cancers occurring after a negative screening test and before the next scheduled screening round. Outcome 3 and 4 will are combined in one single outcome.	1 year for 45-49 years old women

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall cumulative incidence	overall cumulative incidence of breast cancer, including ductal carcinoma in situ. This outcome is a proxy of the excess over-diagnosis eventually induced by tomosynthesis compared with digital mammography.	2 years (+9 months to complete second round assessment)
overall cumulative incidence	overall cumulative incidence of breast cancer, including ductal carcinoma in situ. This outcome is a proxy of the excess over-diagnosis eventually induced by tomosynthesis compared with digital mammography.	4 years (+9 months to complete second round assessment)
detection rate	cancer detected by the screening round on total screened women	This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered
recall rate	number of women referred to assessment after the first leve screening test on total screened women	This outcome is measured at the baseline screening.
positive predictive value	proportion of cancer among women recalled for assessment	This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered
Detection rate of ductal carcinoma in situ	ductal carcinoma in situ detected by the screening round on total screened women	This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered
biopsy rate	number of women undergoing biopsy after the first leve screening test on total screened women	This outcome is measured at the baseline screening.
x-ray dose	average glandular dose receive by women during first level test	This outcome is measured at the baseline screening.
reading time	time needed to read an imaging first level examination	This outcome is measured at the baseline screening.

Collaborators and Investigators

• Sponsor: Azienda Unità Sanitaria Locale Reggio Emilia
• Collaborators: Azienda Ospedaliera Universitaria Integrata Verona; AULSS 9 Scaligera di Verona; IRCCS Policlinico S. Donato, Milano

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 7, 2020
• First Posted (Actual): July 8, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer screening; tomosynthesis
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: RF-2016-02363686

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No