Breast Cancer
Conditions
Keywords
breast cancer screening, tomosynthesis
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTtomosynthesis + 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_TESTdigital 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.
Sponsors
AULSS 9 Scaligera di Verona
IRCCS Policlinico S. Donato, Milano
Azienda Ospedaliera Universitaria Integrata Verona
Azienda USL Reggio Emilia - IRCCS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
SINGLE (Outcomes Assessor)
Masking description
It is not possible to mask the intervention for the patient, care provider, and investigator. Only the assessment of one of the two co-primary outcomes, i.e. cumulative incidence of advanced breast cancer after the first round of screening, can be masked. This will be obtained through a blind review of an external panel of pathologists and radiologists reviewing cases retrieved by cancer registries.
Intervention model description
Women 45-65 participating in the mammographic screening program will be randomized to one round of screening with tomosynthesis + synthetic 2D or with digital mammography. Then all women will be re-screened after 2 years (1 year for women 45-49) for at least one round with digital mammography.
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| advanced cancer incidence | 2 years (+9 months to complete second round assessment) | cumulative incidence of T2+ cancers after first screening round |
| interval cancer incidence | 2 years for 50-65 years old women | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| recall rate | This outcome is measured at the baseline screening. | number of women referred to assessment after the first leve screening test on total screened women |
| positive predictive value | This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered | proportion of cancer among women recalled for assessment |
| Detection rate of ductal carcinoma in situ | This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered | ductal carcinoma in situ detected by the screening round on total screened women |
| overall cumulative incidence | 2 years (+9 months to complete second round assessment) | 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. |
| x-ray dose | This outcome is measured at the baseline screening. | average glandular dose receive by women during first level test |
| reading time | This outcome is measured at the baseline screening. | time needed to read an imaging first level examination |
| biopsy rate | This outcome is measured at the baseline screening. | number of women undergoing biopsy after the first leve screening test on total screened women |
| detection rate | This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered | cancer detected by the screening round on total screened women |
Countries
Italy
Outcome results
None listed