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。治疗完成后，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，以及可能伴随的应激相关细胞因子反应，可能组合（簇）发生。考虑到受影响患者人群的规模，对这一未充分研究的癌症幸存者群体进行有效干预至关重要。本申请的主要目的是响应RFA PA-07-074（前2次提交）和PA- 07-070（第3次提交），严格评价基于正念减压（MBSR）的乳腺癌（BC）计划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）计划在治疗完成后改善患者结局的程度;（2）MBSR（BC）计划有效的方式（机制）;（3）特定亚组的患者是否从MBSR（BC）计划中获益最多。为了实现这些目标，我们将对330名接受过乳房肿瘤切除术和/或乳房切除术的0期、I期、II期和III期乳腺癌女性进行随机临床试验，这些女性在2年内完成了辅助放疗和/或化疗。这一时期对应于关键的过渡时期，此时正式的治疗已经停止，但残留症状仍然存在。患者将以相等的概率被随机分配到MBSR（BC）计划或稍后提供MBSR（BC）计划的等待常规护理方案。将在基线、6周和12周时进行患者评估，并将包括心理症状（抑郁、焦虑、感知压力）、身体症状（疼痛、疲劳、睡眠功能障碍）、生活质量、生物应激标志物（促炎免疫细胞因子、细胞粘附分子、淋巴细胞亚群）和应激相关激素（皮质醇、儿茶酚胺）的测量。要评估的MBSR（BC）计划是一个临床计划，提供系统的训练，以促进通过自我调节唤醒压力减轻压力。我们的小组已经为乳腺癌幸存者修改了这一计划，并显示了其在减轻症状方面的疗效的初步证据。展望未来，我们将正式测试：（1）MBSR（BC）计划是否会在心理症状、身体症状、生活质量和生物应激标记物方面产生更大的初始（6周）和短期持续（12周）改善;（2）MBSR（BC）项目中的患者报告说，他们的正念增加得更多，对复发的恐惧减少得更多，减少心理和身体症状以及与压力相关的激素，并改善生活质量;（3）MBSR（BC）治疗方案在具有高度焦虑、高度压力感知、低乐观、生活质量差和特定症状的患者（即高度痛苦的患者）中效果最好。公共卫生相关性：在乳腺癌治疗后，幸存者经常会经历单独或更常见的集群出现的衰弱症状。有限的研究和治疗方案已经建立，以尽量减少乳腺癌幸存者的这种高发病率。这项研究将正式评估一种基于强化冥想的减压干预措施，以确定它是否能有效改善乳腺癌幸存者的心理和身体症状、生活质量和生物压力标志物。如果这种干预措施被证明是有效的，则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.