PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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 (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D). 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.
BACKGROUND: 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.
BACKGROUND: ACTRN12621000009819.
METHODS: 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 (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D). 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.
BACKGROUND: 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.
BACKGROUND: ACTRN12621000009819.
摘要：
背景：确定的个人和家族风险因素共同导致女性患乳腺癌或卵巢癌的风险。现有的临床服务提供高风险基因致病变异的基因检测，以调查这些风险，但有关常见基因组变异作用的最新信息，以多基因风险评分(PRS)的形式，提供了进一步个性化乳腺癌和卵巢癌风险评估的潜力。来自队列研究的数据支持综合风险评估的潜力，以改善有针对性的风险管理，但这种方法在临床实践中的经验是有限的。
方法：多基因风险调整试验是一项澳大利亚多中心前瞻性随机对照试验，综合风险评估包括个人和家庭风险因素，包括乳腺和卵巢PRS与标准治疗。这项研究将招募女性，不受癌症的影响，在家族性癌症诊所进行预测测试，以确定已知乳腺癌（BC）或卵巢癌（OC）易感基因（BRCA1，BRCA2，PALB2，CHEK2，ATM，RAD51C,RAD51D)。基于阵列的基因分型将用于产生乳腺癌(313个SNP)和卵巢癌(36个SNP)PRS。已经为该试验开发了一套材料，包括用于患者同意和问卷调查的在线门户，和临床医生教育计划，以培训医疗保健提供者使用综合风险评估。长期跟进将评估风险和管理建议的差异，患者风险管理意图和依从性，患者报告的经验和结果，以及个性化风险评估对卫生服务的影响。
背景：本研究已获得PeterMacCallum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审的出版物和会议演示文稿传播，直接对参与者。
背景：ACTRN12621000009819。
方法：多基因风险调整试验是一项澳大利亚多中心前瞻性随机对照试验，综合风险评估包括个人和家庭风险因素，包括乳腺和卵巢PRS与标准治疗。这项研究将招募女性，不受癌症的影响，在家族性癌症诊所进行预测测试，以确定已知乳腺癌（BC）或卵巢癌（OC）易感基因（BRCA1，BRCA2，PALB2，CHEK2，ATM，RAD51C,RAD51D)。基于阵列的基因分型将用于产生乳腺癌(313个SNP)和卵巢癌(36个SNP)PRS。已经为该试验开发了一套材料，包括用于患者同意和问卷调查的在线门户，和临床医生教育计划，以培训医疗保健提供者使用综合风险评估。长期跟进将评估风险和管理建议的差异，患者风险管理意图和依从性，患者报告的经验和结果，以及个性化风险评估对卫生服务的影响。
背景：本研究已获得PeterMacCallum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审的出版物和会议演示文稿传播，直接对参与者。
背景：ACTRN12621000009819。
