PRiMo is a trial of the use of polygenic risk scores in clinical practice designed to identify the optimal method of assessing potentially high-risk women and personalising breast cancer risk management.
Hypothesis: Personalised assessment of the risk of breast cancer that includes the polygenic risk score, along with rare high/moderate-risk breast cancer genes, family history information and personal risk factors, will provide more effective targeted risk management that maximises cancer risk reduction while minimising the medical burden and adverse effects for patients and the cost to the health system.
Design: a randomised clinical trial of full genomic risk assessment for unaffected women from high-risk families referred to a specialist centre for assessment.
The trial compares an approach that counsels and recommends personalised management advice to women based on their assessed breast cancer risk, incorporating:
The modifying effects of common genomic variation (the PRS)
Rare pathogenic variants
Residual cancer family history
…with the current ‘single gene’ risk assessments and management advice.
The trial involves national recruitment through the network of Australian Familial Cancer Centres. Personalised risk assessment will be implemented at FCCs through a standard protocol and patients randomised to standard care will have the option of crossing over to receive a PRS modified risk assessment at 1 year.
Outcomes: Trial end-points include: differences in risk assessment, risk-management intentions and outcomes and prospective evaluation of the accuracy/calibration of risk assessment against clinical outcomes (cancer events).
Additional assessments include a program of patient-focused evaluations to assess acceptability/feasibility of PRiMo risk assessment, and a health services evaluation simulating lifetime outcomes and cost-effectiveness.
The trial is registered on ANZCTR: ACTRN12621000009819