Thornton Lisa M, Andersen Barbara L, Carson William E
Department of Psychology, Ohio State University, Columbus, OH, 43210, USA.
Cancer Immunol Immunother. 2008 Oct;57(10):1471-81. doi: 10.1007/s00262-008-0485-6. Epub 2008 Mar 8.
A period of tumor growth precedes the clinical detection of breast cancer recurrence. We explore immune, endocrine, and behavioral parameters during this period.
We conducted a phase III clinical trial in which women with surgically treated stage II/III breast cancer (N = 227) were randomized to receive a psychological intervention or assessment-only and then regularly assessed for 10 years. Patients who recurred (R, n = 48) were matched with patients remaining disease-free (DF, n = 48) on demographic and prognostic characteristics, treatment, and duration of disease-free follow-up. Data at three assessment points, occurring, on average, 17, 11, and 4 months before the recurrence was detected clinically, with equivalent time points for the disease-free group, were examined. Mixed-effects models tested for group differences in immune cell counts and function as well as endocrine and behavioral parameters.
In the 17 months prior to recurrence detection, patients exhibited higher white blood cell count, neutrophil, lymphocyte, and natural killer cell counts, relative to DF patients. R patients also showed higher cortisol, worse physical functioning, fatigue, and quality of life. Follow-up analyses showed patients with local recurrences to differ from those with distant recurrence, with the former exhibiting elevated natural killer cell cytotoxicity, lymphocyte proliferative response, fatigue, pain, and emotional distress (depression, anxiety), and the latter exhibiting higher neutrophil, lymphocyte, and natural killer cell counts.
Patients who would recur showed reliable biobehavioral alterations more than a year prior to their diagnosis. This novel observation may contribute to our understanding of the disease relapse processes.
在乳腺癌复发的临床检测之前,肿瘤有一段生长时期。我们探索了这一时期的免疫、内分泌和行为参数。
我们进行了一项III期临床试验,将接受手术治疗的II/III期乳腺癌女性患者(N = 227)随机分为接受心理干预组或仅接受评估组,然后进行为期10年的定期评估。复发患者(R,n = 48)与无病患者(DF,n = 48)在人口统计学和预后特征、治疗以及无病随访时间上进行匹配。检查了在临床检测到复发前平均17、11和4个月的三个评估点的数据,无病组有等效的时间点。混合效应模型测试了免疫细胞计数和功能以及内分泌和行为参数的组间差异。
在复发检测前的17个月里,相对于无病患者,复发患者的白细胞计数、中性粒细胞、淋巴细胞和自然杀伤细胞计数更高。复发患者还表现出更高的皮质醇水平、更差的身体功能、疲劳和生活质量。随访分析显示,局部复发患者与远处复发患者存在差异,前者表现出自然杀伤细胞细胞毒性升高、淋巴细胞增殖反应、疲劳、疼痛和情绪困扰(抑郁、焦虑),而后者表现出更高的中性粒细胞、淋巴细胞和自然杀伤细胞计数。
复发患者在诊断前一年多就出现了可靠的生物行为改变。这一新颖的观察结果可能有助于我们理解疾病复发过程。