INTERNET INTERVENTION FOR BRCA1/BRCA2 UNINFORMATIVES

描述（由申请人提供）：BRCA1和BRCA2 （BRCA1/2）突变基因检测是有乳腺癌或卵巢癌家族史的女性常规临床护理的一部分。然而，在大多数接受检测的女性中，这些基因的突变并没有被发现。这种“缺乏信息”的结果并不能排除遗传易感性对这些癌症的可能性。乳腺癌和卵巢癌的绝对风险是异质性的，必须根据对家庭谱系的分析来估计。鉴于这种复杂性，目前没有针对BRCA1/2无信息者的标准咨询方法、风险评估模型或风险管理指南。此外，由此产生的不确定性与痛苦有关。尽管结果不明确的女性患原发性或对侧乳腺癌或卵巢癌的风险可能不是最高的，但相当大比例的女性考虑降低风险手术（RRS），并且在管理决策方面的决策冲突与BRCA1/2突变携带者相当。建议不进行RRS的高风险非告密者遵循类似于BRCA1/2携带者的强化监测方案。到目前为止，还不知道这些妇女是否遵守了这些指导方针。这项随机对照试验的目的是开发和评估在测试后遗传咨询（常规护理，UC）后进行的辅助网络干预（AWI）。我们将评估UC与UC + AWI对心理社会、生活质量和管理结果的相对影响，从而解决关于BRCA1/2无信息患者在UC之上的辅助干预的“增值”的创新问题。在渥太华框架和Baum的基因测试适应模型的指导下，我们将评估AWI影响患者预后的机制，并确定最可能和最不可能从AWI干预中受益的女性。这种干预有可能使无信息者受益- BRCA1/2测试参与者中最大的亚组。如果有效，这一干预措施可以传播给每年接受无信息检测结果的数千名妇女。这项研究的结果将广泛适用于其他高风险人群，他们也接受了不具信息性的基因检测结果。随着我们走向“个性化”医疗，缺乏信息的检测结果将变得越来越普遍，这使得诸如此类的干预措施变得越来越重要。公共卫生相关性：本研究将设计和评估一种辅助的基于网络的干预措施，用于接受无信息的BRCA1/2基因检测结果的妇女，以及乳腺癌和卵巢癌风险增加的异质性妇女。通过促进知情决策，希望这些妇女能够实施适合其风险水平的乳腺癌和卵巢癌风险管理决策，从而对健康和生活质量产生积极影响，并最终降低这些癌症的发病率和死亡率。

DESCRIPTION (provided by applicant): Genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations is part of routine clinical care for women with a family history of breast or ovarian cancer. However, a mutation in these genes is not identified in most women who pursue testing. Such "uninformative" results do not rule out the possibility of an inherited susceptibility to these cancers. The absolute risks for breast and ovarian cancer are heterogeneous and must be estimated based upon an analysis of the family pedigree. Given this complexity, there are currently no standard counseling approaches, risk estimation models, or risk management guidelines for BRCA1/2 uninformatives. Moreover, the resulting uncertainty has been associated with distress. Even though women with uninformative results may not be at the highest risk of developing a primary or contralateral breast cancer or ovarian cancer, a substantial proportion consider risk reducing surgery (RRS), and decisional conflict regarding management decisions is comparable to those of BRCA1/2 mutation carriers. High-risk uninformatives who do not pursue RRS may be advised to follow an enhanced surveillance regimen similar to BRCA1/2 carriers. To date it is not known whether these women adhere to these guidelines. The goal of this randomized controlled trial is to develop and evaluate an adjunct web-based intervention (AWI) to be administered after post-test genetic counseling (usual care, UC). We will evaluate the relative impact of UC versus UC + AWI on psychosocial, quality of life, and management outcomes, thus addressing innovative questions regarding the 'value-added' of an adjunct intervention over and above UC for BRCA1/2 uninformatives. Guided by the Ottawa Framework and Baum's model of adaptation to genetic testing, we will assess the mechanisms by which AWI impacts patient outcomes and identify women most and least likely to benefit from the AWI intervention. This intervention has the potential to benefit uninformatives - the largest subgroup of BRCA1/2 testing participants. If effective, this intervention could be disseminated to the thousands of women who receive uninformative test results annually. The results of this study will be broadly transportable to other high-risk populations who also receive uninformative genetic test results. As we move toward "personalized" medicine, uninformative test results will become increasingly common, making interventions such as this increasingly relevant. PUBLIC HEALTH RELEVANCE: This study will design and assess an adjunct Web-based intervention for women who receive uninformative BRCA1/2 gene testing results, and in whom increased risks for breast and ovarian cancer are heterogeneous. By facilitating informed decision making, it is hoped that these women will implement breast and ovarian cancer risk management decisions appropriate to their risk level, leading to positive effects on well being and quality of life, and ultimately, to reduced morbidity and mortality from these cancers.