PNI and Decision Making in Women Diagnosed with DCIS

描述(申请人提供)：乳腺癌的诊断以及乳腺癌治疗的负担都会使女性面临情绪困扰的风险，这可能会损害与癌症相关的免疫功能。在过去的十年里，由于筛查乳房X光检查的广泛使用，被诊断为导管原位癌(DCIS)的女性人数有所增加。由于对DCIS的自然历史了解有限，DCIS的临床管理面临着越来越大的挑战。因此，患有DCIS的妇女面临着艰难的治疗选择，这些选择不仅必须与癌症复发的风险权衡，还必须与她们的个人价值观相权衡。值得注意的是，人们对被诊断为DCIS的女性的心理需求知之甚少。我们的初步数据表明，患有DCIS的女性有较高的情绪障碍、焦虑和感觉到的压力，这些都伴随着免疫调节失调。这种心理反应对癌症控制机制的影响是相当大的。心理神经免疫学(PNI)多学科领域的广泛证据表明，情绪困扰会损害免疫功能，包括NK细胞活性和细胞因子平衡。NK细胞和细胞因子参与癌症控制，有助于保护个体免受肿瘤起始、原发肿瘤生长、肿瘤转移和感染性疾病的侵袭。因此，这项拟议的研究将使用PNI框架来调查新诊断为DCIS的妇女的心理和免疫反应的动态。此外，还将评估治疗决策对这些妇女的心理内分泌免疫反应的作用。研究的具体目的是：1)评估情绪障碍、焦虑和心理压力增加对确诊为DCIS(0期)乳腺癌患者在诊断和治疗前后4个时间段免疫功能的影响。2)确定决策冲突是否在情绪障碍、焦虑和心理应激对诊断为DCIS的女性免疫功能的影响中起中介作用。3)通过确定决策特征(决策风格、控制偏好和满意度)是否对诊断为DCIS的女性经历的决策冲突水平进行调节，以及(B)决策冲突对诊断为DCIS的女性所报告的情绪障碍、焦虑和心理压力是否起中介作用，对DCIS诊断女性的心理压力和决策做出的调节模型进行评估。新诊断为DCIS的妇女(N=122)将被纳入。前瞻性重复测量设计将用于评估诊断、治疗和治疗后随访阶段的DCIS妇女的情绪、状态焦虑、心理应激、血清皮质醇和免疫功能(NK细胞和细胞因子)。结果将从时间上进行分析，并与一组匹配的非癌症女性进行比较。所获得的知识将通过洞察认知因素(决策)在DCIS女性心理-内分泌-免疫反应中的作用来推进PNI的科学。这种洞察力可能被用来指导管理决策冲突的方法的发展，这将减少乳腺癌女性以及其他面临高风险治疗决定的人群的心理痛苦，并支持免疫功能。

DESCRIPTION (provided by applicant): Both the diagnosis of breast cancer as well as the burden of breast cancer treatment put women at risk for emotional distress that may impair cancer-related immune function. The past decade has witnessed an increase in the number of women diagnosed with ductal carcinoma in situ (DCIS) due to the widespread use of screening mammography. DCIS is a growing clinical management challenge as there is limited knowledge of the natural history of DCIS. As a result women with DCIS face difficult treatment choices that must be weighed against not only the risk of cancer recurrence but also their personal values. Remarkably, there is little understanding of the psychological needs of women diagnosed with DCIS. Our preliminary data suggest that women with DCIS have elevated levels of mood disturbance, anxiety, and perceived stress, which are accompanied by immune dysregulation. The implication of such a psychological response upon cancer control mechanisms is considerable. Extensive evidence from the multidisciplinary field of psychoneuroimmunology (PNI) has demonstrated that emotional distress impairs immune function, including NK cell activity and cytokine balance. NK cells and cytokines participate in cancer control and contribute to the protection of an individual from tumor initiation, primary tumor growth, tumor metastasis, and also infectious disease. Therefore, the proposed study will use a PNI framework to investigate the dynamics of the psychological and immunological response of women newly diagnosed with DCIS. In addition, an evaluation will be made of the role of treatment decision-making on the psycho-endocrine-immune response of these women. The specific aims are to: 1) Evaluate the effect of increased mood disturbance, anxiety, and psychological stress on immune function in women who are diagnosed with DCIS (Stage 0) breast cancer at 4 time periods surrounding diagnosis and treatment. 2) Determine whether decisional conflict mediates the effects of mood disturbance, anxiety, and psychological stress on immune function in women who are diagnosed with DCIS. 3) Evaluate a mediation and moderation model of psychological stress and decision making in women diagnosed with DCIS by determining whether: (a) decision making characteristics (decision style, control preference, and satisfaction) moderate the level of decisional conflict experienced by women diagnosed with DCIS and (b) decisional conflict mediates mood disturbance, anxiety, and psychological stress reported by women diagnosed with DCIS. Women newly diagnosed with DCIS (N=122) will be enrolled. A prospective repeated measures design will be used to evaluate mood, state anxiety, psychological stress, serum cortisol, and immune function (NK cells and cytokines) of women with DCIS across the phases of diagnosis, treatment, and post-treatment follow-up. Results will be analyzed with respect to time and in comparison to a group of matched women without cancer. The knowledge obtained will advance the science of PNI by providing insight to the role of a cognitive factor (decision making) on the psycho-endocrine-immune response in women with DCIS. This insight may be used to guide the development of ways to manage decision conflict, which will reduce psychological distress and support immune function in women with breast cancer, as well as other populations facing high stakes treatment decisions.