Using Polygenic Risk Modification to improve breast cancer prevention
Summary: 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, and
- 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
Peter MacCallum Cancer Centre & Royal Melbourne Hospital
QIMR Berghofer Medical Research Institute
Garvan Institute of Medical Research
School of Clinical Sciences at Monash Health, Monash University
Investigators & Researchers
Joanne McKinley, Dr Lara Petelin, Dr Laura Forrest, Lyon Mascarenhas, Rebecca Purvis, Sharne Limb, Simone McInerny | Parkville Familial Cancer Centre Research Group, Peter MacCallum Cancer Centre
Dr Amanda Willis, Angela Pearce, Lucas Mitchell, Steven He | Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research
Chathu Jayawardana, Helen Tsimiklis, Fleur Hammet | Precision Medicine Laboratory, School of Clinical Sciences at Monash Health, Monash University
Prof Melanie Bahlo, Dr Samaneh Farashi | The Walter and Eliza Hall Institute of Medical Research
Site Principal & Associate Investigators
Dr Abi Ragunathan, A/Prof Judy Kirk | Familial Cancer Service, Westmead Hospital
Dr Ainsley Campbell, Jasmina Bojadzieva, Lucinda Salmon*| Clinical Genetics Service, Austin Health
Dr Annabel Goodwin, Rebecca Harris,| Department of Cancer Genetics, Royal Prince Alfred Hospital
Camron Ebzery, Dr Helen Mar Fan, Rachel Austin, Carol-Ann Verrenkamp, Melanie Boon, Belinda Creighton, Bree Ryan, Rozanna Alli, Simon Troth, Dr Di Milnes* | Genetic Health Queensland, Royal Brisbane and Women's Hospital
Dr Eryn Dow, Dr Nicola Poplawski, Jacqueline Armstrong | Adult Genetics Unit, Royal Adelaide Hospital
A/Prof Kathy Tucker, Rachel Williams, Dr Lesley Andrews | Hereditary Cancer Clinic, Prince of Wales Hospital
A/Prof Marion Harris, Courtney Smyth | Familial Cancer Centre, Monash Health
Dr Mathew Wallis, Denisse Garza | Tasmanian Clinical Genetics Service, Royal Hobart Hospital
Dr Michael Field, Dr Georgina Schlub | Family Cancer Service, Royal North Shore Hospital
A/Prof Nicholas Pachter, Dr Gargi Pathak | Familial Cancer Program, Genetics Services of Western Australia
Prof Paul James, Prof Ingrid Winship, Dr Michael Bogwitz, Alexandra Lewis, Tiffany O'Brien, Shelby Taylor, Joanne Isbister | Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre & Royal Melbourne HospitalA/Prof Yoland Antill, Dr Lynne McKay, Dr Lucy Gately, A/Prof Lara Lipton | Familial Cancer Clinic, Cabrini Health
Development of Training and Education Program
Dr Tatiane Yanes, Dr Aideen McInerney-Leo, Dr Amanda Willis, Bronwyn Terrill, Courtney Wallingford, Dr Holly Keane, Dr Laura Forrest, Lauren McKnight, Mary-Anne Young, Dr Maatje Scheepers-Joynt, Prof Paul James, Rachel Williams, Simone McInerny
Pathology Laboratory Service Providers
Peter MacCallum Cancer Centre, Pathology Queensland, NSW Pathology, SA Pathology, PathWest
The trial will be offered to unaffected women who have been referred to a participating specialist service (Familial Cancer Clinic) in Australia for predictive testing for a pathogenic variant in a high or moderate risk breast (+/- ovarian) cancer-associated gene (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D) previously detected in a genetic relative.
NEW SOUTH WALES
Camperdown NSW 2050
St Leonards NSW 2065
Westmead NSW 2145
Randwick NSW 2031
Herston QLD 4029
Adelaide SA 5000
Hobart TAS 7000
Heidelberg VIC 3084
Malvern VIC 3144
Clayton VIC 3168
Melbourne VIC 3000
Melbourne VIC 3000
Subiaco WA 6008
This research is supported by Love Your Sister in association with the National Breast Cancer Foundation, Australia.