Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Parkville Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
BMJ Open. 2024 Aug 5;14(8):e087874. doi: 10.1136/bmjopen-2024-087874.
Established personal and familial risk factors contribute collectively to a woman's risk of breast or ovarian cancer. Existing clinical services offer genetic testing for pathogenic variants in high-risk genes to investigate these risks but recent information on the role of common genomic variants, in the form of a Polygenic Risk Score (PRS), has provided the potential to further personalise breast and ovarian cancer risk assessment. Data from cohort studies support the potential of an integrated risk assessment to improve targeted risk management but experience of this approach in clinical practice is limited.
The polygenic risk modification trial is an Australian multicentre prospective randomised controlled trial of integrated risk assessment including personal and family risk factors with inclusion of breast and ovarian PRS vs standard care. The study will enrol women, unaffected by cancer, undergoing predictive testing at a familial cancer clinic for a pathogenic variant in a known breast cancer (BC) or ovarian cancer (OC) predisposition gene (, , , , , , ). Array-based genotyping will be used to generate breast cancer (313 SNP) and ovarian cancer (36 SNP) PRS. A suite of materials has been developed for the trial including an online portal for patient consent and questionnaires, and a clinician education programme to train healthcare providers in the use of integrated risk assessment. Long-term follow-up will evaluate differences in the assessed risk and management advice, patient risk management intentions and adherence, patient-reported experience and outcomes, and the health service implications of personalised risk assessment.
This study has been approved by the Human Research Ethics Committee of Peter MacCallum Cancer Centre and at all participating centres. Study findings will be disseminated via peer-reviewed publications and conference presentations, and directly to participants.
ACTRN12621000009819.
已确立的个人和家族风险因素共同导致女性罹患乳腺癌或卵巢癌的风险。现有的临床服务提供针对高风险基因中致病性变异的基因检测，以调查这些风险，但最近关于常见基因组变异（以多基因风险评分 (PRS) 的形式）作用的信息为进一步个性化乳腺癌和卵巢癌风险评估提供了潜力。来自队列研究的数据支持综合风险评估改善靶向风险管理的潜力，但这种方法在临床实践中的经验有限。
多基因风险修正试验是一项澳大利亚多中心前瞻性随机对照试验，对包括个人和家族风险因素在内的综合风险评估进行了研究，包括纳入乳腺癌和卵巢癌 PRS 与标准护理。该研究将招募未患癌症的女性，她们在家族癌症诊所接受预测性检测，以检测已知乳腺癌（BC）或卵巢癌（OC）易感性基因中的致病性变异（、、、、、、）。基于阵列的基因分型将用于生成乳腺癌（313 SNP）和卵巢癌（36 SNP）PRS。该试验开发了一整套材料，包括用于患者同意和问卷的在线门户，以及一个临床医生教育计划，以培训医疗保健提供者使用综合风险评估。长期随访将评估评估风险和管理建议、患者风险管理意图和依从性、患者报告的体验和结果以及个性化风险评估对卫生服务的影响方面的差异。
这项研究已获得彼得麦卡伦癌症中心人类研究伦理委员会和所有参与中心的批准。研究结果将通过同行评议的出版物和会议报告以及直接向参与者传播。
ACTRN12621000009819。
