Tailored Screening for Breast Cancer in Premenopausal Women

Study Overview
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Brief Summary
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The Tailored Breast Screening Trial (TBST) is a population-based, non-inferiority randomised trial aimed at evaluating the impact of tailored screening strategies addressed to premenopausal women, by using breast density as indicator of risk. 44-45 years old women will be enrolled and invited to undergo a digital mammography. Women are then randomly allocated in two arms. In the intervention arm, women will receive a tailored screening strategy according to breast density. The aim of this study is to assess the impact of a longer screening interval and the reduction of side effects for premenopausal women.

Detailed Description
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Introduction: the Tailored Breast Screening Trial (TBST) is a population-based, non-inferiority randomised trial aimed at evaluating the impact of a change in the screening protocol in a service screening practice. Tailored means that the use of a breast density classification allocates women to a longer interval, decreasing the number of screening rounds in the 45-50-year age range. Density of the breast at the baseline is considered as an indicator of risk and also as a masking factor. The aim of this study is to assess the impact of a longer interval and the reduction of side effects for women allocated to the intervention group. In this study, any further intervention is offered to high-density women who are followed-up according to the usual care interval, since the study aimed at decreasing the screening burden. Methods 44- 45 years old women resident in the screening centre catchment area will be invited to attend for mammography screening and will be asked for informed consent in order to be included in the study. After the enrolment, they will receive a high quality digital mammography; two views and breast density will be classified according with the BI-RADS classification. Women are randomly allocated either to an usual care group or to the intervention group. In the intervention group, women with a dense breast (3-4 categories in BI-RADS) will be invited again after 1 year, while the lower-density group in the intervention arm will be invited after 2 years. After the age of 50, all women will continue to be screened in the usual service screening programme. Density of the breast will be read by 2 readers, and controversies will be solved by a consensus. Allocation of women is blinded to the mammography readers. EXPECTED RESULTS: the outcomes are: 1. cumulative incidence of interval-cancer cases by intention to treat grouping and by density group, aimed at assessing the non inferiority of screening performance; 2. cumulative incidence of T2+/node-positive status breast cancer cases between arms and by protocol. Screening performance parameters will be evaluated at each screening round. Interim and outcome analysis are expected at 3 and 6 years average follow-up, respectively, starting from the beginning of the screening. SAMPLE SIZE: the non-inferiority limit is derived from the accepted level of interval cancers in women 50-69 years, which was considered acceptable by the European Community Guidelines. Assuming a 70%BI-RADS 1-2 at the baseline on the basis of the digital mammography experience, the estimated sample size with a power of 90% is 16,596 women per arm.

Official Title
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Tailored Screening for Breast Cancer in Premenopausal Women. A Translational, Randomized Population-based Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Tailored screening according to breast density
* Other: Annual invitation to mammography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women 44-45 years old resident in the screening area Exclusion Criteria: previous diagnosis of invasive or in situ breast cancer women with family high risk for breast cancer previous diagnosis of other cancers in the last 5 years early menopause women or in hormone replacement therapy

Ages Eligible for Study
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Minimum Age: 44 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: invitation to mammography screening<br>44-45 years old women in this arm are invited to attend for a mammography screening every 1 year. After the age of 50, all women will continue to be screened in the usual service screening programme. | Other: Annual invitation to mammography<br>* Annual interval mammography screening according to international guidelines for women younger than 50 years old<br>|
| Experimental: invitation to tailored screening<br>44-45 years old women in this arm with a dense breast (3-4 categories in BI-RADS) at the baseline mammography are invited again after 1 year, while the lower-density group in the intervention arm are invited after 2 years. After the age of 50, all women will continue to be screened in the usual service screening programme. | Other: Tailored screening according to breast density<br>* Different interval of mammography screening according to breast density<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of cumulative incidence of interval cancer cases by arm and by density group | An interval cancer is, according to European guidelines for quality assurance, a primary breast cancer which is diagnosed in a woman who had a screening test negative for malignancy within a time period equal to the screening interval. Interval cancers will be retrieved by linking the cancer registry and screening archive. The cumulative incidence of interval cancers is the number of interval cancers divided by the number of screened women | three and six years | 
| Comparison of cumulative incidence of T2+/node-positive status breast cancer cases by arm and by density group. | The cumulative incidence of T2+/N+ breast cancer is the number of cancers T2+/N+, regardless the modality of detection (screen-detected, interval cancer, etc.), divided by the number of screened women | three and six years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of false positive rates by arm and by density group | The false positive rate is measured as the sum of women with a positive mammography in a screening round without a breast cancer divided by the sum of screened women in the same round. | 3 and 6 years | 
| Comparison of cumulative incidence of breast cancer cases by arm and by density group. | The cumulative incidence of breast cancer is the cumulative number of breast cancers divided by the number of enrolled women.Breast cancer cases will be retrieved by linking the of enrolled women with cancer registry information | 3 and 6 years | 
| Comparison of attendance to mammography screening by arm and by density group. | The attendance to mammography screening is measured as the number of women attending screening mammography on the number of invited women. | 1, 2, 3, 4, 5 and 6 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast density, breast cancer, risk-based screening, Tailored breast cancer screening, premenopausal women