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

• ClinicalTrials.gov Identifier: NCT04590560
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: October 19, 2020
• Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Information provided by (Responsible Party): Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Tracking Information

• First Submitted Date: October 12, 2020
• First Posted Date: October 19, 2020
• Last Update Posted Date: October 19, 2020
• Actual Study Start Date: February 6, 2020
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 12, 2020)

To compare the cumulative incidence of stage 2 or higher breast cancer between different screening intervals [ Time Frame: 6 years ]

Cumulative breast cancer risk will computed as the ratio between the number of stage 2 or higher cancers and the total number of women in the arm. The comparison between arms will be performed using the two proportion Z-test. 95% confidence intervals will also be computed

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 12, 2020)

• Participation in screening [ Time Frame: 6 years ]
  number of participating women within 3 months since invitation)/(total invited women). It will be computed for each screening round and overall as average of round participation
• contamination proportion (use of mammography) within two screening rounds (in women referred to 2-year interval) [ Time Frame: 6 years ]
  number of women referred to 2-year interval and performing a mammogram within two screening round)/number of women referred to 2-year interval The indicator will be computed only for women randomized to arm 2 and for women referred to 2-year arm in arm 3
• Breast cancer detection [ Time Frame: 6 years ]
  number of women with BC diagnosis at screening / number of total screened women
• overall recall rate [ Time Frame: 6 years ]
  number of women recalled for further assessment/ number of total screened women.
• rate of recall with an invasive procedure (biopsy) [ Time Frame: 6 years ]
  number of women recalled for further assessment with a biopsy/ number of total screened women
• interval Breast Cancer rate [ Time Frame: 6 years ]
  number of cancers occurring after a negative mammography and before the date of the next planned appointment/ number of total screened women
• cumulative Breast Cancer incidence [ Time Frame: 6 years ]
  Cumulative incidence of BC including baseline test
• resource expenditure [ Time Frame: 6 years ]
  Mean costs for each attending woman in every of the following processes: Coordination and organization; Invitation; First level mammography; Diagnostic assessment (invasive and non invasive)
• prevalence of dense breast in the target population [ Time Frame: 6 years ]
  women with BI-RADS A, B, C, and D/total women included in the tailored arm

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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).

Masking: None (Open Label)
Primary Purpose: Prevention

• Condition: Breast Cancer

Intervention

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

women will be screened for breast cancer using tomosynthesis and synthetic 2D mammography with an interval defined according to their randomization arm for a follow-up period of 6 years;

Study Arms

• No Intervention: 1-year screening interval
  Women will follow the normal screening program (they will be invited to screen every year)
• Experimental: 2-year screening interval
  Women will be invited to screen every two years
  Intervention: Diagnostic Test: screening for breast cancer with tomosynthesis and synthetic 2D mammography performed at different interval compared to actual clinical practice
• Experimental: 3-tailored screening interval
  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)
  Intervention: Diagnostic Test: screening for breast cancer with tomosynthesis and synthetic 2D mammography performed at different interval compared to actual clinical practice

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 12, 2020): 60000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2026
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 45 Years to 49 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Oriana Nanni; +39 0543 739100; oriana.nanni@irst.emr.it

Contact: Chiara Zingaretti; cc.ubsc@irst.emr.it

• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04590560
• Other Study ID Numbers: IRST174.22
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Study Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Collaborators: Not Provided

Investigators

• Study Chair: Fabio Falcini, MD; IRST IRCCS
• Principal Investigator: Livia Giordano, MD; AOU Città della Salute e della Scienza di Torino
• Principal Investigator: Marco Zappa, MD; ISPRO Firenze

• PRS Account: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Verification Date: October 2020