Facilitated Education and Testing in BRCA Positive Families

遗传咨询和检测通常从受乳腺癌或卵巢癌影响的家庭成员开始 癌如果在该“索引患者”中确定了致病性变异（PV），则鼓励她与患者沟通 和她有危险的亲戚一起该索引患者的一级和二级亲属分别有50%和25%的风险， 同样的PV。对该变体进行有针对性的基因检测具有巨大的潜在好处- 特别是对于那些没有受到癌症影响的人。在BRCA 1/2中继承PV的女性在55- 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 患前列腺癌乳腺癌和胰腺癌的风险增加学习一个人携带PV中确定的 家庭允许妇女采取明确的行动，以减少其癌症风险，并允许男子参加高， 建议对男性BRCA 1/2携带者进行风险监测。此外，男人和女人谁知道， 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， 向他们的后代保证他们没有携带家族性PV的风险。尽管有这些明显的好处， 遗传咨询的比例很低，只有28-57%的一级和二级亲属接受检测。这种低 尽管交流率很高，但遗传咨询和检测率仍然很低。然而，准确性和 所传达信息的质量不明确，而且普遍存在其他实际障碍。 令人惊讶的是，目前还没有旨在提高这一人群摄取率的试验。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，直接接触遗传学提供者，包括网络资源， 临床转诊与较高的咨询和检测率相关。这些发现沿着低 在当前临床实践中的采用强调了需要改进用于识别， 对遗传性乳腺卵巢癌家系的亲属进行教育和检测。在拟议的随机 对照试验，我们将测试一种组合干预，提供基于网络的考前教育， 简化基于电话的遗传咨询（W+T），以个人的一级和二级亲属， BRCA 1/2检测结果呈阳性。我们将招募426名一级和二级亲属 有25-50%机会携带PV的患者，并将其随机分配至W+T组与泌尿系护理（UC）组。我们将 在随机化前进行基线调查，然后在1个月和6个月后进行随访调查 随机化我们的主要成果是遗传咨询和遗传检测的吸收。二次 结果包括心理社会结果、检测到的突变数量和预防/监测的采用情况 行为。本研究以健康信念模式和知情选择模式为指导， 通过开发和评价一种针对以下疾病的干预措施， 在最高风险水平的个体，可能产生改善的癌症结果。

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.