Facilitated Education and Testing in BRCA Positive Families

遗传咨询和检测通常从患有乳房或卵巢疾病的家庭成员开始 癌症。如果在这位“首发患者”身上发现了致病变异(PV)，那么她就会被鼓励进行交流 和她有危险的亲戚在一起。此指标患者的一级和二级亲属分别有50%和25%的风险。 携带相同的光伏病毒。对这种变异进行有针对性的基因测试有巨大的潜在好处-- 尤其是那些没有患过癌症的人。在BRCA1/2中继承PV的女性年龄为55岁- 患乳腺癌的风险为70%，患卵巢癌的风险为16%-45%。继承PV的男性是 患前列腺癌、乳腺癌和胰腺癌的风险增加。了解到其中一个携带在 家庭允许女性采取明确的行动来降低她们的癌症风险，并允许男性参与高风险 对男性BRCA1/2携带者推荐的风险监测计划。此外，了解到这一点的男男女女 他们不携带家族性PV，可以避免不必要的风险降低和筛查干预，以及 让他们的后代放心，他们没有携带家族性PV的风险。尽管有这些明显的好处，但 遗传咨询的比例很低，只有28%-57%的一级和二级亲属接受了检测。这么低 尽管交流的比率很高，但遗传咨询和检测的比率仍然存在。然而，精确度和 所传达的信息的质量不明确，而且在理解方面还存在其他实际障碍。 令人惊讶的是，还没有任何试验旨在提高这一人群的摄取率。这 这意味着错失了降低与各种癌症相关的发病率、死亡率和成本的机会。 观察性研究表明，来自遗传提供者的直接接触包括网络资源和 临床转介与更高的咨询和测试接受度相关。这些发现以及Low 当前临床实践中的摄取强调了改进标准方法以识别、 对遗传性卵巢癌家族的亲属进行教育和检测。在建议的随机化 对照试验，我们将测试一种组合干预，它提供基于网络的考前教育和 简化基于电话的遗传咨询(W+T)，为符合以下条件的个人的一级和二级亲属提供咨询 最近收到了阳性的BRCA1/2检测结果。我们将招募426名一级和二级亲属 他们有25%-50%的机会携带PV，并将他们随机分配到W+T与普通护理(UC)。我们会 在随机化之前进行基线调查，然后在1个月和6个月后进行跟踪调查 随机化。我们的主要成果是接受遗传咨询和基因检测。次要的 结果包括心理社会结果、检测到的突变数量和接受预防/监测。 行为。这项研究在健康信念模型和知情选择模型的指导下，将有 通过为以下目的设计的干预措施的开发和评估的实际临床意义 处于最高风险水平的个人，可能会改善癌症结果。

Genetic counseling and testing typically starts with a family member who is affected with breast or ovarian cancer. If a pathogenic variant (PV) is identified in this `index patient,' then she is encouraged to communicate with her at-risk relatives. First- and second-degree relatives of this index patient are at 50% and 25% risk for carrying the same PV. Undergoing targeted genetic testing for this variant has enormous potential benefits - particularly for those who have not been affected with cancer. Women who inherit a PV in BRCA1/2 are at 55- 70% risk of developing breast cancer and 16-45% risk of developing ovarian cancer. Men who inherit a PV are at increased risk for prostate, breast and pancreatic cancer. Learning that one carries the PV identified in the family allows women to take definitive actions to reduce their cancer risk and allows men to participate in high- risk surveillance programs recommended for male BRCA1/2 carriers. Further, men and women who learn that they do not carry the familial PV, can avoid unnecessary risk reduction and screening interventions and reassure their offspring that they are not at risk for carrying the familial PV. Despite these clear benefits, uptake of genetic counseling is low and only 28-57% of first- and second-degree relatives undergo testing. This low rate of genetic counseling and testing occurs despite high rates of communication. However, the accuracy and quality of the information communicated is not clear and additional practical barriers to uptake are common. Surprisingly, there have been no trials designed to improve the rate of uptake in this population. This represents a missed opportunity to reduce morbidity, mortality and costs associated with a variety of cancers. Observational studies suggest that direct contact from the genetics provider including Web resources and clinical referral is associated with higher counseling and testing uptake. These findings along with the low uptake in current clinical practice underscore the need to improve the standard approach for identifying, educating and testing relatives from hereditary breast ovarian cancer families. In the proposed randomized controlled trial, we will test a combination intervention which provides Web-based pre-test education and streamlined telephone-based genetic counseling (W+T) to first- and second-degree relatives of individuals who have recently received a positive BRCA1/2 test result. We will recruit 426 first- and second-degree relatives who have a 25-50% chance of carrying a PV and randomize them to W+T vs. Usual Care (UC). We will conduct a baseline survey prior to randomization and then follow-up surveys at 1- and 6-months post randomization. Our primary outcomes are the uptake of genetic counseling and genetic testing. Secondary outcomes include psychosocial outcomes, number of mutations detected and uptake of preventive/surveillance behaviors. This study, which is guided by the Health Belief Model and the Informed Choice Model, will have practical clinical significance through the development and evaluation of an intervention designed for individuals at the highest level of risk, potentially yielding improved cancer outcomes.