What is the Best Interval to Screen Women 45-49 and 70-74 for Breast Cancer? (MISS)

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Status: Enrolling

Conditions: Breast Cancer

Treatments: Diagnostic Test: screening for breast cancer with tomosynthesis and synthetic 2D mammography performed at different interval compared to actual clinical practice

Study type: Interventional

Funder types: Other

Identifiers

NCT04590560

IRST174.22

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60,000 estimated patients

Sex: Female

Ages: 45 to 49 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

60,000 participants in 3 patient groups

1-year screening interval

No Intervention group

Description:

Women will follow the normal screening program (they will be invited to screen every year)

2-year screening interval

Experimental group

Description:

Women will be invited to screen every two years

Treatment:

Diagnostic Test: screening for breast cancer with tomosynthesis and synthetic 2D mammography performed at different interval compared to actual clinical practice

3-tailored screening interval

Experimental group

Description:

the screening interval will be decided 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)

Treatment:

Diagnostic Test: screening for breast cancer with tomosynthesis and synthetic 2D mammography performed at different interval compared to actual clinical practice