MBSR Symptom Cluster Trial for Breast Cancer Survivors

描述（由申请人提供）：乳腺癌是女性中最常见的癌症。治疗结束后，乳腺癌幸存者经常会出现残留症状，包括疼痛、疲劳、睡眠障碍、焦虑、抑郁和对复发的恐惧。这种广泛的治疗后症状，以及可能伴随的与应激相关的细胞因子反应，可能以组合（集群）的形式发生。考虑到这一受影响患者群体的规模，对这一研究不足的癌症幸存者群体进行有效干预是至关重要的。本申请的主要目的是响应前两份提交的RFA PA-07-074和第三份提交的PA- 07-070，严格评估正念减压（MBSR）乳腺癌（BC）项目在乳腺癌幸存者中的疗效。具体来说，我们的目标是确定：(1)MBSR （BC）项目在治疗完成后改善患者预后的程度；(2) MBSR （BC）项目有效的方式（机制）；(3)是否有特定的亚组患者从MBSR （BC）项目中获益最多。为了实现这些目标，我们将进行一项随机临床试验，对330名接受过乳房肿瘤切除术和/或乳房切除术的0、I、II和III期乳腺癌患者进行随机临床试验，这些患者在完成辅助放疗和/或化疗治疗后的2年内。这一时期对应于正式医疗治疗停止，但残余症状仍然存在的关键过渡时期。患者将以等概率随机分配到MBSR （BC）计划或等待的常规护理方案中，随后提供MBSR （BC）计划。患者评估将在基线、6周和12周进行，包括心理症状（抑郁、焦虑、感知压力）、身体症状（疼痛、疲劳、睡眠障碍）、生活质量、生物压力标志物（促炎免疫细胞因子、细胞粘附分子、淋巴细胞亚群）和压力相关激素（皮质醇、儿茶酚胺）的测量。被评估的MBSR （BC）项目是一个临床项目，提供系统的训练，通过自我调节对压力的觉醒来促进压力减轻。我们的小组对乳腺癌幸存者的这个项目进行了修改，并初步证明了它在减轻症状方面的有效性。接下来，我们将正式测试：(1)与常规护理相比，MBSR （BC）项目在心理症状、身体症状、生活质量和生物应激标志物方面是否有更大的初始（6周）和短期持续（12周）改善；(2) MBSR （BC）项目的患者报告正念能力有了更大的提高，对复发的恐惧也有了更大的减少，这反过来又减少了心理和身体症状以及与压力相关的激素，并提高了生活质量；(3) MBSR （BC）方案在表现为高焦虑、高感知压力、低乐观、生活质量差和特定症状（即高度痛苦患者）的患者中效果最好。乳腺癌治疗后，幸存者往往会出现单发或多发的衰弱症状。已经建立了有限的研究和治疗方案，以尽量减少乳腺癌幸存者中这种高发病率。本研究将正式评估以密集冥想为基础的减压干预，以确定其是否对改善乳腺癌幸存者的心理和生理症状、生活质量和生物应激标志物有效。如果这种干预措施被证明是有效的，就有可能扩大其使用范围，以尽量减少其他类型癌症以及严重的非癌症健康疾病的发病率。

DESCRIPTION (provided by applicant): Breast cancer is the most prevalent form of cancer among women. After treatment completion, breast cancer survivors frequently experience residual symptoms including pain, fatigue, sleep dysfunction, anxiety, depression, and fear of recurrence. This wide range of post-treatment symptoms, and possibly concomitant stress-related cytokine responses, may occur in combination (clusters). Effective interventions for this understudied group of cancer survivors are paramount given the size of this affected patient population. The primary goal of this application in response to RFA PA-07-074 for the first 2 submissions, and PA- 07-070 for this 3rd submission is to rigorously evaluate the efficacy of the Mindfulness Based Stress Reduction (MBSR) Breast Cancer (BC) program among breast cancer survivors. Specifically, we aim to determine: (1) the extent to which the MBSR (BC) program improves patient outcomes after treatment completion; (2) the manner (mechanisms) by which the MBSR (BC) program is effective; and (3) if particular subgroups of patients derive the most benefit from the MBSR (BC) program. To achieve these aims, we will conduct a randomized clinical trial of 330 women with Stage 0, I, II, and III breast cancer who have undergone lumpectomy and/or mastectomy, and are within 2 years of completion of treatment with adjuvant radiation and/or chemotherapy. This period corresponds to the critical transition time when formal medical treatment has ceased, yet residual symptoms remain. Patients will be randomly assigned in equal probability to the MBSR (BC) program or a waitlisted usual care regimen that is later offered the MBSR (BC) program. Patient assessments will be made at baseline, 6 weeks, and 12 weeks, and will include measures of psychological symptoms (depression, anxiety, perceived stress), physical symptoms (pain, fatigue, sleep dysfunction), quality of life, biological stress markers (pro-inflammatory immune cytokines, cellular adhesion molecules, lymphocyte subsets) and stress-related hormones (cortisol, catecholamines). The MBSR (BC) program to be evaluated is a clinical program that provides systematic training to promote stress reduction by self-regulating arousal to stress. Our group has modified this program for breast cancer survivors and shown preliminary evidence of its efficacy in reducing symptoms. Going forward, we will formally test whether: (1) the MBSR (BC) program results in greater initial (6 week) and short-term sustained (12 week) improvements in psychological symptoms, physical symptoms, quality of life, and biological stress markers compared to Usual Care; (2) patients in the MBSR (BC) program report greater increases in mindfulness and larger reductions in fear of recurrence which, it turn, reduce psychological and physical symptoms and stress-related hormones, as well as improve quality of life; and (3) the efficacy of the MBSR (BC) program is greatest among patients who present with high anxiety, high perceived stress, low optimism, poor quality of life, and specific symptom profiles (i.e. highly distressed patients). PUBLIC HEALTH RELEVANCE: Project Narrative After treatment for breast cancer, survivors often experience debilitating symptoms that occur singly, or more commonly, in clusters. Limited research and treatment regimens have been established to minimize this high degree of morbidity among breast cancer survivors. This study will formally evaluate an intensive meditation- based stress reduction intervention to determine if it is efficacious in improving psychological and physical symptoms, quality of life, and biological stress markers among breast cancer survivors. If this intervention is shown to be efficacious, the possibility exists of extending its use to minimize morbidity for other types of cancers, as well as severe non-cancer health disorders.