The FORECEE research project is a unique investigation of the molecular and bacterial/viral factors that may predict a woman’s risk of developing breast, ovarian, womb and cervical cancer (the 4Cs).
The project will develop Women’s cancer risk IDentification tests, or (WID) tests, investigate the ethical, legal and regulatory implications of the tests, analyse strategies for implementation and their cost effectiveness, and work with key decision makers across Europe to discuss how the tests could be rolled out.
Developing the Women's Cancer Risk Identification Tests
Six clinical sites will collect samples from women to support development of the WID tests.
The unique focus of the FORECEE programme looks beyond just cancer genetics and, through analysis of epigenetic markers, into how each woman's body responds to environmental and lifestyle factors which can raise or decrease the risk of developing cancer. We will also investigate the bacterial/viral factors (metagenetic factors). By bringing these factors together, FORECEE aims to develop tests that predict a woman's individual risk of developing female cancers, and to investigate the best ways of incorporating these into large-scale and cost effective screening programmes available to whole populations.
WID tests will take into account the different needs of women depending on their age.
Women below the age of 45-50 are, in the absence of a DNA mutation such as BRCA1/2 or Lynch syndrome, unlikely to develop a female cancer. In addition, non-inherited risk factors are unlikely, at this age, to have accumulated sufficiently for detection. Nevertheless, two challenges remain for women <45-50 years and these will be addressed by FORECEE’s premenopausal WID test:
- Presence of a high risk germline mutation (BRCA1/2 mutation or Lynch syndrome): only approximately half of high risk mutations are detected based on family history. The FORECEE project will investigate whether a DNA methylation marker in cervical cells would be able to assess the presence of these mutations;
- The specificity of HPV (human papillomavirus) screening for cervical cancer is too low; the FORECEE project aims to increase this specificity to 98% through the combination of an epigenetic and/or metagenetic analysis in the same sample.
For women older than 45-50 years, we will develop a post-menopausal WID test that will be a 5-yearly assessment of the 5-10 year risk for all four women’s cancers.
The FORECEE tests, by identifying a woman’s risk of cancer, would be used to target those women who are most likely to benefit from health promotion, screening, and preventive actions. This offers clear advantages; for example, screening resources would be targeted towards those women with the highest likelihood of benefit while at the same time reducing screening interventions for women at lower risk, thus producing more benefit at a lower cost.
Ethical, Legal and Regulatory Implications of the FORECEE Project.
The team at The Harding Center for Risk Literacy, led by Dr Felix Rebitschek, will develop ways of communicating the complex medical information behind testing a woman’s individual cancer risk in a way that is accessible and comprehensible to both doctors and patients. Specifically, the potential benefits and risks of the test need to be presented in a transparent manner. The researchers will start by conducting a survey of the target group to find out exactly what information women need and to gauge their general acceptance of the test.
Investigations of the ethical and legal aspects of developing and implementing the risk prediction tests will be investigated by the Professor Inez de Beaufort at the Erasmus Medical Center in Rotterdam. She will conduct a thorough study of the literature surrounding the different ethical and legal aspects of the approach, review the results of the Harding Center’s survey and organise debates with leading experts in policy, ethics, law, anthropology and sociology. Together their findings will feed into recommendations for future health policy.
Strategies for Implementation
FORECEE will develop models to evaluate how best to implement the WID tests within health systems.
Professor Ewout Steyerberg’s team at the Erasmus Medical Center and Professor Uwe Siebert’s team at Oncotyrol will work together to examine whether implementing WID tests at a population level could be cost effective and whether it offers a positive balance between long-term benefits and the risk of harm to women.
Their decision analytic model will follow international standards and key principles of health technology assessment (HTA), such as the International Society For Pharmacoeconomics and Outcomes Research-Society for Medical Decision Making (ISPOR-SMDM) Joint Task Force Modeling Good Research Practices and international key principles for HTA.