Clinical trial NCT04590560: What is the Best Interval to Screen Women 45-49 and 70-74 for Breast Cancer?
Official title: What is the Best Interval to Screen Women 45-49 and 70-74 for Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Breast cancer, screening, diagnosis, mammography
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 60000
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible women signing the written informed consent will be randomized with a 1:1:1 ratio to:

Arm 1: 1-year screening interval; Arm 2: 2-year screening interval; Arm 3: tailored screening interval on the basis of breast density. Women with very dense breast (BI-RADS category D) will be referred to 1-year interval whereas women with less dense breast to 2-year interval (BI-RADS category A, B, C).
Primary purpose: PREVENTION

Brief summary: Italian, multicenter, study aimed at defining the best interval for screening women 45-49 and 70-74 years for Breast Cancer (BC). This research project includes (1) a controlled, prospective randomized non-inferiority trial to determine the optimal screening interval for women aged 45-49, with and without high mammographic density, (2) a retrospective data collection, with the same purpose, on screening performed by women aged 70-74, and (3) a qualitative research to define the best communication strategy.

Detailed description: According to the 2006 European guidelines, the target age for mammography screening is 50-69 years. For women aged 40-49, effectiveness is less and less certain. For those over 70, the most important concern is overdiagnosis. In Europe, so far, both age groups have been invited to screen only in a few countries and regional areas, including some Italian regions. Recently, new European guidelines have been published, developed in the framework of the European Commission Initiative on Breast Cancer. Although with caution, they recommend screening for both women aged 45-49 and those aged 70-74. The recommended interval is 2 or 3 years in the first case and 3 years in the second. The quality of the evidence on which these recommendations are based is defined as very low. Particularly for women aged 45-49, the new European guidelines indicate the need for a research effort, based on comparative studies, on the effectiveness of different screening intervals. This responsibility also falls on Italy, which is the only European country where women aged 45-49 are invited on an annual basis. Therefore, a research project is proposed which includes (1) a controlled, prospective randomized non-inferiority trial to determine the optimal screening interval for women aged 45-49, with and without high mammographic density, (2) a retrospective data collection, with the same purpose, on screening performed by women aged 70-74, and (3) a qualitative research to define the best communication strategy.

To define the best interval for screening women 45-49 years old a three-arm multicenter randomized non-inferiority trial will be conducted. Women signing the written informed consent will be randomized with a 1:1:1 ratio to:

Arm 1: 1-year screening interval; Arm 2: 2-year screening interval; Arm 3: tailored screening interval on the basis of breast density. Women with very dense breast (Breast Imaging-Reporting and Data System -BI-RADS- category D) will be referred to 1-year interval whereas women with less dense breast to 2-year interval (Breast Imaging-Reporting and Data System -BI-RADS- category A, B, C).

Enrollment will last 2.5 years and all women will be followed for 6 years. 60,000 women will be enrolled.

The primary objective is to compare the cumulative incidence of stage 2 or higher breast cancer between different screening intervals and this will be evaluated at the end of the 6-year follow-up period.

At the same time, data from all women registered in screening archives who have had a negative mammogram at the age of 69-71 years will be collected and analyzed. The data will be retrieved up to the age of 78 and will concern screening mammograms as well as other screening procedures (e.g. biopsies) and also mammograms performed outside the program. Data from screening and outpatient information systems as well as from cancer registries will be used.

To identify the best strategy to communicate changes in screening protocols, especially when the new protocol would be less intensive than the actual one, a qualitative research will be conducted. In particular the following steps will be considered:

* Focus groups for discussing, with women from target population and health care professionals, key arguments identified in a preliminary research (i.e. scientific literature and case-studies research), with particular focus on how they should be translated into communication strategies.
* Pre-test of the study's communication material through web-based semi-structured interviews to eligible women and key-informants.
* Assessment of the effectiveness of the communication material through web-based semi-structured interviews to participants, that may bring insights on how planning communication strategies for the implementation of new screening protocols.

Eligibility criteria: Inclusion Criteria:

1. Women invited for their first or second mammography (45 or 46 y/o) presenting for screening;
2. Willingness and ability to comply with scheduled visits;
3. Written informed consent obtained prior to performing any protocol-related procedures.

Exclusion Criteria:

1. Pregnancy status;
2. Personal history of prior breast carcinoma, either invasive or ductal carcinoma in situ (DCIS) diagnosis;
3. Ascertained heredo-familial risk according to the standard family history used in screening programs;
4. Participation in another clinical trial on BC screening;
5. Inability to provide signed informed consent.

Primary outcomes:
measure: To compare the cumulative incidence of stage 2 or higher breast cancer between different screening intervals
timeFrame: 6 years
Secondary outcomes:
measure: Participation in screening
timeFrame: 6 years
measure: contamination proportion (use of mammography) within two screening rounds (in women referred to 2-year interval)
timeFrame: 6 years
measure: Breast cancer detection
timeFrame: 6 years
measure: overall recall rate
timeFrame: 6 years
measure: rate of recall with an invasive procedure (biopsy)
timeFrame: 6 years
measure: interval Breast Cancer rate
timeFrame: 6 years
measure: cumulative Breast Cancer incidence
timeFrame: 6 years
measure: resource expenditure
timeFrame: 6 years
measure: prevalence of dense breast in the target population
timeFrame: 6 years
Other outcomes:
Locations:
city: Meldola (FC)
country: Italy
facility: Irst Irccs
state: FC
city: Firenze
country: Italy
facility: Istituto per lo studio, la prevenzione e la rete oncologica (ISPRO)
city: Forlì
country: Italy
facility: AUSL Romagna
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza
Study officials:
affiliation: IRST IRCCS
name: Fabio Falcini, MD
role: STUDY_CHAIR
affiliation: A.O.U. Città della Salute e della Scienza
name: Livia Giordano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ISPRO Firenze
name: Marco Zappa, MD
role: PRINCIPAL_INVESTIGATOR
References: