PRISMA study: Personalised RISk-based MAmmascreening

In most EU-countries, women in a specific age group are invited for breast
cancer screening. This *one-size-fits-all* screening approach, based only on
age, fails to take advantage of the growing ability to predict individual
variation in risk of breast cancer and to translate that information into
better screening outcomes. The PRISMA study (Personalised RISk-based
MAmmascreening) will focus on how to make screening for breast cancer more
effective and efficient by targeting women who are most likely to benefit and
reducing exposure to screening in those women who are more likely to experience
the harms. Potential implementation of this new approach presents a number of
major challenges. One includes the acceptability for women in the target
population. Furthermore, extending the personalised paradigm to the field of
breast cancer screening will raise additional questions with respect to
medico-legal and ethical considerations.

Objective 1: To collect information on risk factors and biomarkers in a
screening cohort, develop a tailor-made risk prediction model and,
subsequently, model the impact of adapting breast cancer screening policy to
populations at varying levels of risk, i.e. to assess whether moving from the
current *one-size-fits-all* screening policy to more personalised risk-based
screening regimens can optimise the efficacy of breast cancer screening using
the same resources.

Objective 2: To make an inventory on communication, medico-legal and ethical
considerations related to personalised risk-based screening and present a
synthesis at an interdisciplinary expert meeting, along with results of the
project, in order to discuss implications and recommendations for current vs
personalised risk-based screening policies.

Observational cohort study.

Participants will be asked to complete a web-based questionnaire on currently
established risk factors for breast cancer. Breast density will be
automatically assessed on the unprocessed screening mammograms. For a part of
the study population, the study includes donating blood samples one time (2 x
10 ml; 2 x 6 ml) in order to determine plasma hormone levels, RNA profiles of
blood platelets, other blood markers and to extract DNA for genotyping. A
saliva sample (2 ml), instead of a blood sample, will be collected from a small
subsample of the population in order to extract DNA. Risks associated with
participation are confined to the normal risks of taking blood samples (risk of
fainting and of bruising). Since the drawing of blood will be done by
professionals, risks are low. In the mobile screening units, women will first
be asked to complete the online questionnaire and give consent to the analysis
of their unprocessed mammogram. They are also asked if they consent to the
PRISMA-team contacting them in case they are diagnosed with breast cancer in
the future. If women consent to this, they will be asked to provide either a
blood or saliva sample after the breast cancer diagnosis. Since a breast cancer
diagnosis indicates a tumultuous time for the woman, a saliva sample could be a
less invasive alternative.