My Personalized Breast Screening

Study Overview
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Brief Summary
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MyPeBS is an international randomized, open-label, multicentric, study assessing the effectiveness of a risk-based breast cancer screening strategy (using clinical risk scores and polymorphisms) compared to standard screening (according to the current national guidelines in each participating country) in detecting stage 2 or higher breast cancers. Women will be differentially screened for 4 years and then, after an end-of-study mammogram, they will return to the routine screening practice. The main study endpoint will be measured at the end of the four years of intervention. Furthermore, follow up data will be collected for 15 years from study entry for evaluation of long-term cumulative breast cancer incidence and breast cancer-specific survival

Official Title
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International Randomized Study Comparing Personalized, Risk-Stratified to Standard Breast Cancer Screening In Women Aged 40-70

Conditions
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Breast Screening

Intervention / Treatment
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* Other: Mammogram
* Other: Ultrasound
* Other: MRI
* Other: Tomosynthesis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female (whether born female or not) Aged 40 to 70 years old (inclusive) Willing and able to comply with scheduled visits, laboratory tests, and other trial procedures Able to provide written informed consent obtained prior to performing any protocol-related procedures Sufficient understanding of any of the languages used in the study Affiliated to a social security/national healthcare system Exclusion Criteria: Personal history of breast carcinoma, either invasive or ductal carcinoma in situ (DCIS) Prior history of atypical breast lesion, lobular carcinoma in situ or chest wall irradiation Known condition or suspicion of a very high risk predisposition to breast cancer: germline mutation of BRCA1/2, PALB2, TP53 or equivalent History of bilateral mastectomy Recent abnormal breast finding under work-up (clinically suspect lesion or BI-RADS 4 or 5 image) Psychiatric or other disorders that are not compatible with compliance to the protocol requirements and follow-up Women who do not intend to be followed-up for 4 years

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard arm<br>Participants will be screened for breast cancer according to current national/regional guidelines and procedures: with a mammogram and/or tomosynthesis (TS) every 1-3 years starting at age 40-50 years, up to age 69-74 years, with or without ultrasound and MRI depending on breast mammographic density and current recommendations. The national/regional guidelines in use in the including center may be subjected to changes during the study. Guidelines and procedures in the standard arm will be updated accordingly. | Other: Mammogram<br>* Every 1-4 years according to the national/regional guidelines or personalised schedule according to risk assessment<br>Other: Ultrasound<br>* As required according to the national/regional guidelines or personalised schedule according to risk assessment<br>Other: MRI<br>* As required according to the national/regional guidelines or personalised schedule according to risk assessment<br>Other: Tomosynthesis<br>* As required according to the national/regional guidelines or personalised schedule according to risk assessment<br>|
| Experimental: Risk-based arm<br>Participants will be screened according to a personalised timetable based on their estimated 5-year risk of developing breast cancer: with a mammography and/or tomosynthesis every 1-4 years with or without ultrasound depending on breast density. Risk estimation will be performed using the following variables: age, family history, previous history of benign breast biopsy, personal hormone and reproductive history, breast mammographic density and genotyping (polygenic risk score). Risk assessment will be conducted using Mammorisk™ for women with at most one first-degree relative with breast or ovarian cancer and using Tyrer-Cuzick™ risk score for those women with more than one first-line first degree relative with breast or ovarian cancer. | Other: Mammogram<br>* Every 1-4 years according to the national/regional guidelines or personalised schedule according to risk assessment<br>Other: Ultrasound<br>* As required according to the national/regional guidelines or personalised schedule according to risk assessment<br>Other: MRI<br>* As required according to the national/regional guidelines or personalised schedule according to risk assessment<br>Other: Tomosynthesis<br>* As required according to the national/regional guidelines or personalised schedule according to risk assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of stage 2 and plus breast cancer (non-inferiority analysis) | The study primary objective is to show non-inferiority of the risk-stratified screening strategy in terms of incidence rate of breast cancer of stage 2 and higher (2+), compared to standard screening. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of stage 2 and plus breast cancer (superiority analysis) | The key secondary objective, if non-inferiority is shown, is to demonstrate superiority of the risk-based screening arm to reduce the incidence rate of stage 2+ breast cancer, compared to standard screening. | 4 years | 
| Rate of morbidity in each arm | Morbidity is defined as false positive imaging findings and benign breast biopsies | 4 years | 
| Subject anxiety in response to risk evaluation | Subject anxiety will be evaluated using the State-Trait Anxiety Inventory (STAI) questionaire, and compared between treatment arms | 4 years | 
| Socio-psychological characteristics of subjects | Socio-psychological characteristics will be evaluated using study specific questions concerning comprehension, information-seeking behavior, satisfaction and socio-demographic and economic status | 4 years | 
| Subject quality of life | Subject quality of life will be evaluated using the EQ-5D quality of life questionnaire | 4 years | 
| Comparison of cost-effectiveness of each strategy | Crude costs, defined as full real costs per stage 2 cancer diagnosis, will be estimated in each arm. The cost-effectiveness of mammographic screening will be calculated by comparing estimated life-years and costs of breast cancer in each arm | 4 years | 
| Incidence of stage-specific breast cancer in each arm (including DCIS) | Comparison of the overall incidence of breast cancer detected in each arm according to AJCC stage | 4 years | 
| Estimates of the rate of detection of clinically non-significant tumours (overdiagnosis) in each study arm | Overdiagnosed breast cancer cases are defined as cancers that would never have been detected clinically, if women had not been screened. Differential overdiagnosis will be measured comparing the cumulative incidence of breast cancer in each arm 15 years after the end of the interventional period of the study. | 15 years | 
| Rate of false negative images and interval cancers in each arm | False negative images: in case of diagnosis of breast cancer in women whose last screening images (including mammogram +/- US and MRI) were considered as Breast Imaging- Reporting and Data System 1 or 2 (BI-RADS 1 or 2) at 6 months maximum before diagnosis. Interval cancers are defined as a breast cancers diagnosed between a negative screening episode - [mammogram classified as normal (BI-RADS ACR 1 or 2 or equivalent) or abnormal mammogram but negative assessment] and the next planned mammogram | 4 years | 
| 10- and 15-year breast cancer specific survival in MyPeBS and in a combined analysis of the Wisdom and MyPeBS studies |  | 15 years | 
| Detection rate of stage 2+ breast cancer in women who had screening tomosynthesis (where and when available) and the rate without tomosynthesis |  | 4 years | 
| Incidence of all stage and stage 2 + breast cancers at 10- and 15-year follow-up |  | 15 years | 
| Incidence of stage 2 + breast cancer in each arm, in women aged 40-49 at inclusion |  | 4 years | 
| Rate of breast cancers identified at second reading in each arm |  | 4 years | 
| Rate of false positive imaging findings and benign breast biopsies in women classified at low risk in risk-based arm |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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standard breast screening - risk-based screening program