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

项目摘要/摘要：据估计，每190名妇女中就有1人携带BRCA1/2致病变异， 这与70岁时患乳腺癌的风险为46%-57%，患卵巢癌的风险为20%-40%有关。 携带者分别占乳腺癌和卵巢癌病例的10%和15%，高达20%的高危患者。 恶性浆液性卵巢癌是最具侵袭性的亚型。尽管有建议说所有卵巢 癌症患者应该接受遗传咨询和检测，而不考虑家族史和发病年龄。 最近的全国性研究表明，只有10%的病例接受了基因检测。这表示未命中 向这些妇女及其高危家庭成员通报她们未来的癌症风险的机会。这个 拟议的研究通过应用追溯测试方法来解决这一护理缺口，以追溯确定 曾被诊断患有卵巢癌的女性。然后这些妇女将被提供遗传咨询， 测试和癌症风险评估。这项研究将利用肿瘤登记来识别以前的病例 过去10年内在两个管理型医疗保健系统(Kaiser)被诊断为卵巢癌 Permanente Northwest和Kaiser Permanente Colorado)。使用存档的病理样本进行 生殖系基因测试将允许在世和已故妇女的家庭成员接受家庭成员 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的病理样本；2)探索伦理、隐私、 以及与已故患者基因测试相关的政策含义，以告知家庭风险；3) 描述在诊断时接受遗传咨询的障碍，包括转诊障碍， 护理途径，以及患者的随访。我们已经组建了一支多学科团队，具有以下专业知识 生物伦理学、遗传流行病学、基因组医学、生物统计学、健康传播学和医学 遗传学。我们将邀请患者、家庭成员、提供者和卫生系统管理员来指导 卵巢癌基因检测障碍的研究设计和表征。我们独特的综合健康 信息系统、肿瘤登记和存档的病理标本使我们非常适合 调查追溯测试的可行性。为追溯测试的可行性生成证据 使用肿瘤登记和存档的病理样本对指导未来至关重要 实施超越卵巢癌的此类计划。

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.