Genetic Risk Analysis in Ovarian Cancer (GRACE) Administrative Supplement

项目总结/摘要 据估计，每190名妇女中就有1名携带BRCA 1/2的致病性变异，这与46-57%的风险相关。 70岁时患乳腺癌和卵巢癌的风险分别为20-40%。携带者占乳腺的10%和15% 和卵巢癌病例，分别高达20%和高级别浆液性卵巢癌病例，最 攻击亚型尽管建议所有卵巢癌病例都应接受遗传咨询， 和测试，无论家族史和发病年龄，最近的一项全国性研究表明，只有10%的 10例患者接受了基因检测。这意味着错过了向这些妇女及其高危群体提供信息的机会。 家庭成员的未来癌症风险。拟议补充项目的母研究旨在 通过采用追溯测试方法，追溯性地确定患有 卵巢癌的早期诊断既往诊断为卵巢癌且未接受过 基因检测将提供遗传咨询，检测和癌症风险评估。这项研究将利用 肿瘤登记，以确定在过去24年内诊断出的卵巢癌既往病例， 医疗保健系统（Kaiser Permanente Northwest和Kaiser Permanente科罗拉多）。使用 用于生殖系基因检测的存档病理学样本将允许在世和已故的家庭成员 妇女获得家族遗传癌症风险信息。我们将评估：1）可行性和障碍 与使用肿瘤登记和存档病理学样本进行追溯测试方法相关，以及 2)探索与已故患者基因检测相关的伦理、隐私和政策影响， 告知家族风险。这项母研究将为使用肿瘤进行追溯测试的可行性提供证据 登记和存档病理学样本，这对于指导未来实施此类 卵巢癌以外的项目该补充项目将以母研究的目标为基础， 使用生物伦理学研究方法来描述社会决定因素对接受基因治疗的影响， 在指数卵巢癌诊断的风险信息。该补充将利用 母研究，并将使用Kaiser Permanente Northwest和Kaiser确定的研究人群 永久科罗拉多以及一个额外的网站，凯撒永久华盛顿。混合方法 一种联合收割机方法将通过图表审查和抽象的电子病历分析与定性 进行分析，以掌握护理途径，以确定健康的社会决定因素在特定阶段的作用， 这些护理途径，如转诊和吸收。本增刊的结果将在调查结果的基础上加以扩展 通过确保公平获取遗传风险信息，为未来的追溯研究提供信息 所有患有卵巢癌和其他遗传性癌症的患者。

PROJECT SUMMARY/ABSTRACT An estimated 1 in 190 women carry a pathogenic variant in BRCA1/2, which is associated with an 46-57% risk of breast cancer and 20-40% risk of ovarian cancer by age 70. Carriers account for 10% and 15% of breast and ovarian cancer cases, respectively, and up to 20% of high-grade serous ovarian cancer cases, the most aggressive subtype. Despite recommendations that all ovarian cancer cases should receive genetic counseling and testing, irrespective of family history and age at onset, a recent national study indicated that only 10% of cases underwent genetic testing. This represents a missed opportunity to inform these women and their at-risk family members about their future cancer risk. The parent study of the proposed supplemental project aims to address this care gap by applying a traceback testing approach to retrospectively identify women who have a prior diagnosis of ovarian cancer. Individuals with a prior diagnosis of ovarian cancer who have not received genetic testing will be offered genetic counseling, testing, and cancer risk assessment. This study will leverage tumor registries to identify prior cases of ovarian cancer diagnosed within the past 24 years at two managed care healthcare systems (Kaiser Permanente Northwest and Kaiser Permanente Colorado). The use of archived pathology samples for germline genetic testing will allow family members of both living and deceased women to receive familial genetic cancer risk information. We will assess: 1) the feasibility of and barriers associated with using tumor registries and archived pathology samples for a traceback testing approach, and 2) explore the ethical, privacy, and policy implications associated with genetic testing in deceased patients to inform familial risk. This parent study will generate evidence on the feasibility of traceback testing using tumor registries and archived pathology samples which is critically important to guide future implementation of such programs beyond ovarian cancer. This supplemental project will build upon the aims of the parent study by using a bioethical research approach to characterize the impact of social determinants on receipt of genetic risk information at the index ovarian cancer diagnosis. The supplement will leverage the infrastructure of the parent study and will use the study population identified at Kaiser Permanente Northwest and Kaiser Permanente Colorado as well as an additional site, Kaiser Permanente Washington. A mixed methods approach will combine electronic medical record analysis through chart review and abstraction with qualitative analysis to capture care pathways to characterize the role of social determinants of health at specific points in these care pathways, such as referral and uptake. The results of this supplement will expand upon the findings of the parent study to inform future traceback studies by ensuring equitable access to genetic risk information for all patients with ovarian and other hereditary cancers.