None listed
Conditions
Brief summary
This trial is investigating the efficacy and feasibility of a personalised risk assessment for breast and ovarian cancer, through offering a polygenic risk score. Who is it for? You may be eligible for this trial if you are a woman aged 18 years and above undergoing a predictive test for a known familial mutation in a gene associated with increased risk of breast cancer - BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C or RAD51D at a participating Familial Cancer Clinic. You may also be eligible if you have previously completed predictive testing that detected PALB2, CHEK2, ATM, RAD51C, or RAD51D at a participating Familial Cancer Clinic. Study details Participants will be randomly allocated to either the intervention arm, or a waitlist control that will be eligible to receive the personalised risk assessment after 1 year. The intervention arm will receive an integrated, personalised risk assessment and risk management advice, whereas the control arm will receive risk management advice based on the standard risk assessment incorporating the results of single gene testing and family cancer history. Information from this trial will be used to optimise targeted risk management of breast and ovarian cancer, whilst minimising the burden and cost to the health system
Interventions
The intervention is a 'personalised' breast and ovarian cancer risk assessment that includes the modifying effects of common genomic variation (the Polygenic Risk Score (PRS)).
The trial will be offered to unaffected women 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 or RAD51D) previously detected
The intervention is a 'personalised' breast and ovarian cancer risk assessment that includes the modifying effects of common genomic variation (the Polygenic Risk Score (PRS)). The trial will be offered to unaffected women 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 or RAD51D) previously detected in a genetic relative ('single gene' testing). A cohort of unaffected women who have previously tested positive for a moderate risk breast cancer gene (PALB2, CHEK2, ATM, RAD51C, or RAD51D) will also be recruited to the study. The trial will compare the current standard of care with a personalised assessment of the risk of breast and ovarian cancer that includes 'single gene' testing, family history, personal risk factors and research genomic testing (PRS). For participants assigned to the intervention arm an integrated risk assessment will be completed by the study team. The assessment will involve combining basic risk factor information provided by the participant (age, ethnicity, lifestyle risk factors and the family history of cancer) with the result of the predictive gene test from the clinical laboratory and a polygenic risk score calculated by the study team using the genotyping results from the research testing. The PRS will be calculated from an individual's genotyping results as the sum of the log odds associated with previously validated risk allele and a report generated by the central study team using standard methods, including the 'Polygen' tool developed at the Parkville Familial Cancer Centre. All components will be combined to produce a highly personalised risk assessment using the CanRisk tool and the output summarised in a custom report that includes the primary genetic information and a risk summary that describes personalised 5 and 10 year risks for breast and ovarian cancer. The results of the Personalised Risk Assessment and the resulting risk management advice will be provided to the participant by their genetics specialist team in a 60 minute face-to-face (in-person or telehealth) appointment. Risk management advice for each participant will be determined by the managing genetics specialist team and the study team will not be directly involved in their care or provide medical advice to study participants. However, information will be provided to the managing genetics specialist team to ensure a standard approach is used when applying the existing national guidelines for the management of hereditary risk of breast and ovarian cancer (eviQ guidelines, CCNSW) to the personalised risk assessment.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Randomised controlled trial
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Prospective Enrolment: (1) Undergoing a predictive test for a likely pathogenic (Class 4) or pathogenic (Class 5) familial mutation in a gene associated with increased risk of breast cancer - BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D at a participating Familial Cancer Clinic. Retrospective Enrolment: (1) Have previously completed germline testing and been found to harbour a likely pathogenic (Class 4) or pathogenic (Class 5) variant in a breast/ovarian cancer associated ‘moderate risk’ gene: PALB2, CHEK2, ATM, RAD51C, RAD51D at a participating Familial Cancer Clinic. Prospective and Retrospective enrolment (2) Female, unaffected by invasive or in-situ breast cancer or epithelial ovarian cancer (3) Aged 18 years or above and < 80 years (4) Have access to the internet and a computer, tablet or smart phone and a basic level of familiarity with digital platforms.
Exclusion criteria
(1) Unable to read and understand patient study information, including an English language patient information and consent form (2) Have previously undertaken genomic testing that included polygenic risk information for breast or ovarian cancer (3) Undergoing current treatment for a cancer diagnosis. (4) No DNA sample at a participating diagnostic laboratory (5) Known at time of enrolment to have or be at risk for a significant risk-factor for breast or ovarian cancer that is not captured in the PRiMo risk assessment. For example, a diagnosis of Li-Fraumeni syndrome or predictive testing for a variant with an atypical risk in a known gene (hypomorphs).
Outcome results
None listed