STRESS AND IMMUNITY--IMPLICATIONS FOR BREAST CANCER

描述(申请人的描述)精神神经免疫学的进展 提供了明确和令人信服的证据，证明压力会导致 免疫功能。应激诱导的免疫调节可能会影响结果 和乳腺癌的控制。要了解压力对一个人的影响 女性免疫系统及其与乳腺癌控制的关系， 需要对自然主义的应激范式进行评估。基于我们的 初步研究，诊断性乳腺活检的经验提供了 这样一种压力范式。我们的结果表明，迫在眉睫的压力 乳腺活检导致心理压力，神经内分泌激活，以及 自然杀伤细胞活性(NKCA)下降。NK细胞介导 对肿瘤细胞的天然抵抗力，在 肿瘤转移的控制。拟议的试验性研究的目的是 调查可能导致应激反应的潜在介质 NK细胞活性降低。细胞因子的激活对于最佳 NK细胞活性与肾上腺皮质应激激素、皮质醇和 脱氢表雄酮(DHEA)，调节细胞因子的产生模式。 因此，Th1/Th2细胞因子在心理雄激素和NK细胞中的作用 将确定女性乳房活组织检查前后的反应。这个 心理反应将通过评估情绪障碍来衡量， 感觉到的压力和焦虑。此外，心理学的概念是 可能会修改压力感知将被测量并包括，弹性和 连贯感。应激诱导的神经内分泌激活与NK细胞 将根据这些心理测量对活动进行评估。 一种群体内的设计，其中女性经历了高度的心理 应激和低NK细胞活性(活检前)，随后缓解 NK细胞活性的应激和恢复(良性结果的活检后) 将用于跟踪Th1/Th2细胞因子的模式和血浆中 压力荷尔蒙。这些反应在女性患者中的潜在差异 良性与恶性乳腺活检结果将是 下定决心。这项研究的独特之处在于它将提供一个完整的 癌症早期女性的心理-内分泌-免疫概况，如 以及对潜在调解人的作用的理解 应激诱导的免疫抑制。对机制的理解 在应激诱导的NKCA减少的背后有相当大的 不仅对接受乳房活组织检查的女性有影响，而且大多数 对于开发和测试干预措施非常重要 预防和/或控制诊断为乳腺癌的妇女的自然杀伤细胞抑制 癌症。这种干预可以改善对标准治疗的反应， 改善症状管理，从而提高妇女的生活质量 乳腺癌。

DESCRIPTION (Applicant's Description) Advances in psychoneuroimmunology have provided clear and compelling evidence that stress leads to changes in immune function. Stress-induced immune modulation may influence the outcome and control of breast cancer. To understand the effect of stress on a woman's immune system and its relationship to breast cancer control, requires the evaluation of a naturalistic stress paradigm. Based on our preliminary studies, the experience of diagnostic breast biopsy provides such a stress paradigm. Our results show that the stress of impending breast biopsy leads to psychological stress, neuroendocrine activation, and a decrease in natural killer (NK) cell activity (NKCA). NK cells mediate natural resistance against tumor cells, and are particularly important in the control of tumor metastasis. The purpose of the proposed pilot study is to investigate potential mediators that may account for stress-induced reduction in NK cell activity. Cytokine activation is essential to optimal NK cell activity and the adrenocortical stress hormones, cortisol and dehydroepiandrostarons (DHEA), regulate the pattern of cytokine production. Therefore, the role of Thl/Th2 cytokines in the psycho-andocrine and NK cell response of women pro-and post-breast biopsy will be determined. The psychological response will be measured by assessing mood disturbance, perceived stress, and anxiety. Additionally, psychological constructs which may modify stress perception will be measured and include, resilience and sense of coherence. Stress-induced neuroendocrine activation and NK cell activity will be evaluated in the context of these psychological measures. A within groups design in which women experiencing heightened psychological stress and low NK cell activity (pre- biopsy) followed by alleviation of stress and restoration of NK cell activity (post-biopsy with benign results) will be used to follow patterns of Thl /Th2 cytokines and plasma levels of stress hormones. Potential differences in these responses in women with benign versus those with malignant breast biopsy findings will be determined. This study is unique in that it will provide an integrated psycho-endocrine-immune profile of women early in the cancer trajectory, as well as an understanding of the role of potential mediators of stress-induced immune depression. An understanding of the mechanisms underlying the stress-induced reduction of NKCA has considerable implications not only for women undergoing breast biopsy, but most importantly for the development and testing of interventions that can prevent and/or control NK cell depression in women diagnosed with breast cancer. Such intervention may improve the response to standard therapy, improve symptom management, and hence the quality of life of women with breast cancer.