Leveraging tumor registries and pathology specimens to facilitate genetic testing and traceback for ovarian cancer

项目总结/摘要：估计每190名女性中就有1名携带BRCA 1/2致病变异体， 这与70岁时46-57%的乳腺癌风险和20-40%的卵巢癌风险相关。 携带者分别占乳腺癌和卵巢癌病例的10%和15%，高血压患者高达20%。 级浆液性卵巢癌病例中，侵袭性最强的亚型。尽管建议所有卵巢 癌症患者应接受遗传咨询和检测，无论其家族史和发病年龄如何， 最近的全国性研究表明，只有10%的病例接受了基因检测。这是一个错过的 让这些妇女及其高危家庭成员了解她们未来患癌症的风险。的 拟议的研究通过应用回溯测试方法来回顾性地识别 女性谁有卵巢癌的前期诊断。这些妇女将接受遗传咨询， 测试和癌症风险评估。这项研究将利用肿瘤登记来识别先前的病例， 过去10年内在两个管理式医疗保健系统（Kaiser）诊断出卵巢癌 Permanente Northwest和Kaiser Permanente科罗拉多）。使用存档的病理学样本 生殖细胞基因检测将允许在世和已故妇女的家庭成员接受家族遗传学检查。 遗传癌症风险信息。我们将评估：1）使用肿瘤的可行性和障碍 用于追溯测试方法的登记和存档病理学样本; 2）探索伦理，隐私， 以及与已故患者基因检测相关的政策影响，以告知家族风险; 3） 描述在诊断时接受遗传咨询的障碍，包括转诊的障碍， 护理访问和患者随访。我们组建了一个多学科团队， 生物伦理学，遗传流行病学，基因组医学，生物统计学，健康传播和医学 遗传学我们将让患者、家庭成员、提供者和卫生系统管理员参与进来， 研究设计和表征卵巢癌基因检测障碍。我们独特的综合健康 信息系统、肿瘤登记和存档病理标本使我们非常适合 调查回溯测试的可行性。生成关于回溯测试可行性的证据 使用肿瘤登记和存档的病理学样本对指南未来至关重要 这些计划的实施超越了卵巢癌。

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 proposed study addresses this care gap by applying a traceback testing approach to retrospectively identify women who have a prior diagnosis of ovarian cancer. These women will then 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 10 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; 2) explore the ethical, privacy, and policy implications associated with genetic testing in deceased patients to inform familial risk; 3) characterize barriers to receiving genetic counseling at the time of diagnosis, including barriers to referral, care access, and patient follow-up to. We have assembled a multidisciplinary team with expertise in bioethics, genetic epidemiology, genomic medicine, biostatistics, health communication, and medical genetics. We will engage patients, family members, providers, and health system administrators to guide study design and characterize barriers to genetic testing in ovarian cancer. Our unique integrated health information systems, tumor registries, and archived pathology specimens make us ideally suited to investigate the feasibility of traceback testing. Generating evidence on the feasibility of traceback testing using tumor registries and archived pathology samples is critically important to the guide future implementation of such programs beyond ovarian cancer.