INTERNET INTERVENTION FOR BRCA1/BRCA2 UNINFORMATIVES

描述(申请人提供)：BRCA1和BRCA2(BRCA1/2)突变的基因检测是对有乳腺癌或卵巢癌家族史的妇女的常规临床护理的一部分。然而，在大多数进行检测的女性中，没有发现这些基因的突变。这种“缺乏信息”的结果并不排除这些癌症遗传易感性的可能性。乳腺癌和卵巢癌的绝对风险是不同的，必须基于对家系的分析来估计。鉴于这种复杂性，目前还没有针对BRCA1/2非信息性患者的标准咨询方法、风险评估模型或风险管理指南。此外，由此产生的不确定性一直与痛苦有关。尽管结果不具信息性的女性患原发或对侧乳腺癌或卵巢癌的风险可能不是最高的，但仍有相当比例的女性考虑降低风险手术(RR)，有关管理决策的决策冲突与BRCA1/2突变携带者的决策冲突相当。不寻求RRS的高危不知情者可能被建议遵循类似于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这些指导方针。这项随机对照试验的目标是开发和评估在测试后遗传咨询(通常护理，UC)后实施的辅助网络干预(AWI)。我们将评估UC和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非信息性患者在UC之上进行辅助干预的‘附加值’的创新问题。在渥太华框架和鲍姆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，并确定最有可能和最不可能从AWI干预中受益的女性。这种干预有可能使不知情的人受益--BRCA1/2测试参与者中最大的一组。如果有效，这项干预措施可能会传播给每年收到不具信息性的检测结果的数千名妇女。这项研究的结果将广泛传播到其他高危人群，他们也得到了不具信息性的基因测试结果。随着我们走向“个性化”医学，缺乏信息的检测结果将变得越来越普遍，这使得这样的干预措施变得越来越重要。公共卫生相关性：这项研究将为那些接受非信息性BRCA1/2基因检测结果的妇女设计和评估一项基于网络的辅助干预措施，在这些妇女中，乳腺癌和卵巢癌风险的增加是不同的。通过促进知情决策，希望这些妇女将执行适合其风险水平的乳腺癌和卵巢癌风险管理决定，从而对福祉和生活质量产生积极影响，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.