International Randomized Study Comparing Personalized, Risk-Stratified to Standard Breast Cancer Screening In Women Aged 40-70
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- UNICANCER
- Enrollment
- 53,142
- Locations
- 10
- Primary Endpoint
- Incidence rate of stage 2 and plus breast cancer (non-inferiority analysis)
Study Overview
Brief Summary
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 40 Years to 70 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Standard arm
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.
Intervention: Mammogram (Other)
Standard arm
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.
Intervention: Ultrasound (Other)
Standard arm
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.
Intervention: MRI (Other)
Standard arm
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.
Intervention: Tomosynthesis (Other)
Risk-based arm
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.
Intervention: Mammogram (Other)
Risk-based arm
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.
Intervention: Ultrasound (Other)
Risk-based arm
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.
Intervention: MRI (Other)
Risk-based arm
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.
Intervention: Tomosynthesis (Other)
Outcomes
Primary Outcomes
Incidence rate of stage 2 and plus breast cancer (non-inferiority analysis)
Time Frame: 4 years
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.
Secondary Outcomes
- Subject quality of life(4 years)
- Incidence of stage-specific breast cancer in each arm (including DCIS)(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)
- Socio-psychological characteristics of subjects(4 years)
- Incidence rate of stage 2 and plus breast cancer (superiority analysis)(4 years)
- Rate of morbidity in each arm(4 years)
- Subject anxiety in response to risk evaluation(4 years)
- Rate of false positive imaging findings and benign breast biopsies in women classified at low risk in risk-based arm(4 years)
- Comparison of cost-effectiveness of each strategy(4 years)
- Estimates of the rate of detection of clinically non-significant tumours (overdiagnosis) in each study arm(15 years)
- Rate of breast cancers identified at second reading in each arm(4 years)
- Rate of false negative images and interval cancers in each arm(4 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 stage 2 + breast cancer in each arm, in women aged 40-49 at inclusion(4 years)
- Incidence of all stage and stage 2 + breast cancers at 10- and 15-year follow-up(15 years)