Periodic Reporting for period 4 - MyPeBS (International Randomized Study Comparing personalized, Risk-Stratified to Standard Breast Cancer Screening In Women Aged 40-70)
Período documentado: 2022-07-01 hasta 2023-12-31
Since the late 1980s, organised breast cancer screening programmes have been introduced in more and more countries across Europe. The aim of mammography screening is to detect breast cancer as early as possible, primarily in order to reduce the number of breast cancer deaths but also to reduce the severity of the disease and the use of heavy invasive cancer treatments.
These programmes have always used a “one size fits all” strategy whereby women in a target age group (typically between 50-69 years old) are invited for a mammography every 2 to 3 years. This approach has demonstrated benefits on specific mortality. However, it also comes with certain side effects, such as false positive findings, overdiagnosis and associated overtreatment. Furthermore, mammography may induce a small lifetime risk of radiation-induced cancer.
A promising approach to improve mammography screening is personalized, individual risk-based screening. Indeed, each woman has her own individual risk of developing breast cancer, depending on many factors like genetic factors, lifestyle, or hormonal exposure.
Recent scientific advances have largely improved our understanding of breast cancer genetics and other risk factors. We now have accurate risk assessment tools and sufficient knowledge to investigate the advantages of using a new screening approach based on individual risk estimation of breast cancer: this is the goal of MyPeBS.
MyPeBS aims to assess the effectiveness, feasibility and safety of a personalised breast cancer screening strategy, where screening interval and methods used are based on the personal risk of developing breast cancer.
To meet such a goal, at MyPeBS’s core is a multi-centre, international, randomised clinical study that aims at recruiting 85,000 volunteer women aged 40 to 70 years-old and without history of breast cancer, living in Belgium, France, Israel, Italy, the United Kingdom and Spain.
This study will compare two groups of women: half of them will follow the ongoing standard breast screening in their region, and the other half will experiment a personalised strategy where women at higher risk of BC are screened more, and women at a lower risk less. The incidence of stage 2+ breast cancer after 4 years will be compared in each group to determine if a personalised breast screening is at least equivalent (non-inferiority test), or even more efficient (superiority test), than the standard screening.
MyPeBS will also evaluate whether a personalised approach is acceptable for women (psyco-social evaluation), and if the economic resources used with a personalised screening justify the results obtained.
These programmes have always used a “one size fits all” strategy whereby women in a target age group (typically between 50-69 years old) are invited for a mammography every 2 to 3 years. This approach has demonstrated benefits on specific mortality. However, it also comes with certain side effects, such as false positive findings, overdiagnosis and associated overtreatment. Furthermore, mammography may induce a small lifetime risk of radiation-induced cancer.
A promising approach to improve mammography screening is personalized, individual risk-based screening. Indeed, each woman has her own individual risk of developing breast cancer, depending on many factors like genetic factors, lifestyle, or hormonal exposure.
Recent scientific advances have largely improved our understanding of breast cancer genetics and other risk factors. We now have accurate risk assessment tools and sufficient knowledge to investigate the advantages of using a new screening approach based on individual risk estimation of breast cancer: this is the goal of MyPeBS.
MyPeBS aims to assess the effectiveness, feasibility and safety of a personalised breast cancer screening strategy, where screening interval and methods used are based on the personal risk of developing breast cancer.
To meet such a goal, at MyPeBS’s core is a multi-centre, international, randomised clinical study that aims at recruiting 85,000 volunteer women aged 40 to 70 years-old and without history of breast cancer, living in Belgium, France, Israel, Italy, the United Kingdom and Spain.
This study will compare two groups of women: half of them will follow the ongoing standard breast screening in their region, and the other half will experiment a personalised strategy where women at higher risk of BC are screened more, and women at a lower risk less. The incidence of stage 2+ breast cancer after 4 years will be compared in each group to determine if a personalised breast screening is at least equivalent (non-inferiority test), or even more efficient (superiority test), than the standard screening.
MyPeBS will also evaluate whether a personalised approach is acceptable for women (psyco-social evaluation), and if the economic resources used with a personalised screening justify the results obtained.
During the first 18 month- period of the project, the MyPeBS consortium set up all the necessary tools and obtained all the regulatory authorisations to start and run the clinical trial. This included, among other activities:
- preparing and translating all the study related documents, obtaining all required regulatory approvals, implementing all contractual and logistical steps
- building a dedicated GDPR-compliant Web platform allowing study data collection and flow, and enabling personalisation of the interface for each user depending on their country/region, language, screening schedule etc
- developing all the modules required to run the study and connect them to the platform, e.g. e-learning for investigators, e-signature of participation consents, risk score estimation
- setting the saliva DNA extraction and genotyping activities
- developing a communication plan and multilingual communication tools.
The first study participant was recruited in France on July 18th, 2019, followed by Belgium in October and Italy and Israel in December. By early 2020, the accrual rate was rapidly growing and UK was ready to start, but the first general COVID-19 related population lockdowns in Europe forced the MyPeBS study to halt from March 13, 2020. The MyPeBS study resumed only in September 2020, after de-containment of the general population and gradual resumption of organized breast cancer screening activities in the various participating countries. A month later, UK recruited its first participant. Spain joined the consortium as an additional recruiting country.
However, since trial resumption, several successive epidemic waves occurred worldwide. Consequently, despite the 6-months COVID-19 extension automatically granted by the EC in 2020, and despite continuous efforts from the Coordinator and from all partners involved in accrual, study conduct and communication, a detrimental residual effect still remains on recruitment. Indeed, in addition to the very unfavourable to research-general crisis context, both health care professionals involved in the study and potential participants (who are women from the general population, as opposed to patients) are impacted by the COVId-19 pandemics, due to illness, quarantine or other priorities than participating in MyPeBS. This seemed more pronounced than ever with the Omicron wave which started end of 2021 and is still active in a broad range of regions in Europe and in the world.
As of August of 2023, a total of 53,143 women have been recruited in the MyPeBS study, representing 94% of the target population (56,435 participants as per MyPeBS GA Amendment #4 validated on December 20, 2022).
- preparing and translating all the study related documents, obtaining all required regulatory approvals, implementing all contractual and logistical steps
- building a dedicated GDPR-compliant Web platform allowing study data collection and flow, and enabling personalisation of the interface for each user depending on their country/region, language, screening schedule etc
- developing all the modules required to run the study and connect them to the platform, e.g. e-learning for investigators, e-signature of participation consents, risk score estimation
- setting the saliva DNA extraction and genotyping activities
- developing a communication plan and multilingual communication tools.
The first study participant was recruited in France on July 18th, 2019, followed by Belgium in October and Italy and Israel in December. By early 2020, the accrual rate was rapidly growing and UK was ready to start, but the first general COVID-19 related population lockdowns in Europe forced the MyPeBS study to halt from March 13, 2020. The MyPeBS study resumed only in September 2020, after de-containment of the general population and gradual resumption of organized breast cancer screening activities in the various participating countries. A month later, UK recruited its first participant. Spain joined the consortium as an additional recruiting country.
However, since trial resumption, several successive epidemic waves occurred worldwide. Consequently, despite the 6-months COVID-19 extension automatically granted by the EC in 2020, and despite continuous efforts from the Coordinator and from all partners involved in accrual, study conduct and communication, a detrimental residual effect still remains on recruitment. Indeed, in addition to the very unfavourable to research-general crisis context, both health care professionals involved in the study and potential participants (who are women from the general population, as opposed to patients) are impacted by the COVId-19 pandemics, due to illness, quarantine or other priorities than participating in MyPeBS. This seemed more pronounced than ever with the Omicron wave which started end of 2021 and is still active in a broad range of regions in Europe and in the world.
As of August of 2023, a total of 53,143 women have been recruited in the MyPeBS study, representing 94% of the target population (56,435 participants as per MyPeBS GA Amendment #4 validated on December 20, 2022).
MyPeBS first expects to produce clear-cut scientific results and strong recommendations regarding the best-possible screening model between current standard and risk-based screening, in terms of reduction of stage II or higher BC incidence.
Overall with MyPeBS the following impacts are expected:
1. For Women of the general population
• Improve individual patient outcomes and health outcome predictability
• Reduce the overall burden of breast cancer by allowing earlier detection of a breast cancer in women with a higher risk. Such earlier diagnosis is indeed associated with a better prognosis, less treatments needs, less morbidity from the therapies, and lower costs
• Improve the benefit / risk ratio of the of mammography screening by
- reducing the amount of over-diagnosed breast cancers and consequently the overtreatment (unnecessary mammographies and biopsies), by lengthening the screening interval in low risk women;
- obtaining more effective screening in higher risk individuals, especially young women (<40 years old), with a more intensive screening (frequency and exams) allowing earlier detection of advanced stage disease
• Enhance women compliance with organised breast cancer screening by their satisfaction level with screening and prevention measures
• Improve women empowerment towards their personal health
• Pave the way for the development of personalised screening for other types of cancer.
2. For decision makers and health authorities:
• Demonstration of the feasibility, psycho-social acceptability, efficacy and cost-effectiveness of a personalised breast screening program
• Production of recommendations about risk-based screening and associated operational guidelines
• Identification of adequate care pathways models for the delivery of stratified prevention
3. For health care professionals
• Improved awareness on the efficacy of breast cancer prevention
• Better knowledge and understanding of breast cancer risk factors
Overall with MyPeBS the following impacts are expected:
1. For Women of the general population
• Improve individual patient outcomes and health outcome predictability
• Reduce the overall burden of breast cancer by allowing earlier detection of a breast cancer in women with a higher risk. Such earlier diagnosis is indeed associated with a better prognosis, less treatments needs, less morbidity from the therapies, and lower costs
• Improve the benefit / risk ratio of the of mammography screening by
- reducing the amount of over-diagnosed breast cancers and consequently the overtreatment (unnecessary mammographies and biopsies), by lengthening the screening interval in low risk women;
- obtaining more effective screening in higher risk individuals, especially young women (<40 years old), with a more intensive screening (frequency and exams) allowing earlier detection of advanced stage disease
• Enhance women compliance with organised breast cancer screening by their satisfaction level with screening and prevention measures
• Improve women empowerment towards their personal health
• Pave the way for the development of personalised screening for other types of cancer.
2. For decision makers and health authorities:
• Demonstration of the feasibility, psycho-social acceptability, efficacy and cost-effectiveness of a personalised breast screening program
• Production of recommendations about risk-based screening and associated operational guidelines
• Identification of adequate care pathways models for the delivery of stratified prevention
3. For health care professionals
• Improved awareness on the efficacy of breast cancer prevention
• Better knowledge and understanding of breast cancer risk factors