Personalised Risk-based Breast Cancer Prevention and Screening

Study Overview
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Brief Summary
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This is a cohort study, applied research and T3 translational genomics to estimate the impact of genetic risk for breast cancer detection in the screening program. The study group base consists of 28 389 female participants, currently in the age-group 22-79, in the Biobank of Estonian Genome Centre. The study is aimed to demonstrate the usability of personalised approach for adjusting and stratifying screening recommendations, based on predicted genetic risk estimates for breast cancer in the situation, where the genome data could be available from all women who have given informed consent for that. The project includes both the detection of moderate and high hereditary breast cancer risk carriers as well as high risk polygenic risk-score (consisting several single nucleotide polymorphisms) carriers among healthy individuals for application of personalised prevention and screening strategies.

Official Title
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Implementation of a Model for Personalised Risk-Based Breast Cancer Prevention and Screening

Conditions
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Breast Cancer

Intervention / Treatment
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* Diagnostic Test: Mammography outside official screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Available NGS (WGS or WES) data for detection of breast cancer moderate to high genetic risk variants in BRCA1, BRCA2, TP53, STK11, PTEN, CDH1, ATM, PALB2, CHEK2, NBN, NF1 genes; Available genetic (WGS, genotyping) data for PRS calculation, participants in age 40-74 will be further selected; Cohort 2: Available genotyping data; No available NGS data for BRCA1, BRCA2, TP53, STK11, PTEN, CDH1, ATM, PALB2, CHEK2, NBN, NF1 genes; Participants in the age group 40-74 with available genetic data for PRS calculation; Cohort StMG: • Female participants in Estonian Biobank in the age group 50-69 participating at least once in the current Estonian population-based screening program during 2016-2020. Exclusion Criteria: Cohort 1: breast cancer in the medical history; Cohort 2: breast cancer in the medical history. Cohort StMG: none.

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1<br>High monogenic breast cancer risk | Diagnostic Test: Mammography outside official screening<br>* Radiologic study<br>|
| Active Comparator: Cohort 2<br>High polygenic breast cancer risk | Diagnostic Test: Mammography outside official screening<br>* Radiologic study<br>|
| No Intervention: Cohort StMG<br>Standard mammography screening in age 50-69 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of women in the population with genetically higher risk for breast cancer |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of screen-detected breast cancers in different risk groups |  | 3-years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Screening, Genetic risk, Polygenic risk score