شناخت های رفتاری مدیریت استرس افزایش می یابد به نفع پیدا کردن و عملکرد سیستم ایمنی بدن در میان زنان مبتلا به سرطان پستان در مراحل اولیه

Objective This study examined the effect of a cognitive–behavioral stress management (CBSM) intervention on emotional well-being and immune function among women in the months following surgery for early-stage breast cancer. Method Twenty-nine women were randomly assigned to receive either a 10-week CBSM intervention (n=18) or a comparison experience (n=11). The primary psychological outcome measure was benefit finding. The primary immune function outcome measure was in vitro lymphocyte proliferative response to anti CD3. Results Women in the CBSM intervention reported greater perceptions of benefit from having breast cancer compared to the women in the comparison group. At 3-month follow-up, women in the CBSM group also had improved lymphocyte proliferation. Finally, increases in benefit finding after the 10-week intervention predicted increases in lymphocyte proliferation at the 3-month follow-up. Conclusion A CBSM intervention for women with early-stage breast cancer facilitated positive emotional responses to their breast cancer experience in parallel with later improvement in cellular immune function.

For years, psychologists have studied negative psychological states associated with the diagnosis and treatment of breast cancer [1] and [2]. Although the diagnosis and treatment of breast cancer can be stressful at a number of levels, there is evidence that effectively working through this crisis may have positive psychological effects [3], [4] and [5]. Cancer patients have reported that the experience of having cancer has led to fortified personal resources and skills, stronger spirituality, closer relations with significant others, a clearer sense of purpose and changes in life priorities [6], [7], [8], [9], [10] and [11]. Tedeschi and Calhoun [12] suggest that individuals who have struggled with negative life challenges and developed creative solutions to them report that their struggles have had positive effects on their lives. No intervention studies had demonstrated that psychological intervention might facilitate the process by which these positive psychological effects develop until the study by Antoni et al. [13]. In the Antoni et al. study, women with early-stage breast cancer who participated in a 10-week cognitive–behavioral stress management (CBSM) intervention reported increases in finding benefit from the cancer experience compared to the comparison group women [13]. We wondered if these positive changes might result in improved physical health. How might positive psychological changes result in improved physical health? Epel et al. [14] propose a theoretical model where working through stressful experiences can change a person's appraisal of subsequent stressors from a sense of threat to a sense of challenge. This “toughening up” of the stress response renders the individual more resistant to future stressors. Resistance to future stressors could then lead to improved biological outcomes. At this point, however, the literature offers only a hint that experiencing benefits and growth may have beneficial physical manifestations as well as psychological ones. One longitudinal study reported that HIV-positive gay men who were able to find meaning through bereavement of a partner or close friend had a slower rate of CD4 cell decline and had lower AIDS-related mortality at 2–3-year follow-up compared to men who did not find meaning [15]. Changes in immune function may be important for breast cancer patients. While these results must be interpreted with caution as causality has not been determined, there is provocative evidence that deficiencies in immune function, including poor in vitro lymphocyte proliferative response, are related to the course of breast cancer. For example, lymphocyte proliferation in response to autologous tumor antigen was shown to be a significant predictor of 13-year relapse free survival among 77 Stages I and II breast cancer patients [16]. In an earlier study with 142 breast cancer patients, the same group found that patients with a good lymphocyte response to PHA were more likely to have lymphocyte immunity against tumor antigens. Patients with lymphocyte immunity to tumor antigens were more likely to be long-term disease-free survivors [17]. There is also evidence suggesting that an increase in lymphocyte proliferation in response to PHA, measured preoperatively and 1-year postoperatively, is associated with a decreased rate of recurrence at 2-year follow-up among women with Stages I–III breast cancer [18]. The studies above all measured nonspecific mitogen (PHA) stimulation of lymphocyte proliferation. It would be interesting to measure in vitro proliferation in response to specific activation of the T cell receptor, CD3, because this type of stimulation is a closer approximation of the in vivo proliferation mechanism [19]. In sum, participating in a CBSM intervention while “working through” a life stressor such as the diagnosis of breast cancer has been shown to facilitate finding benefit in the cancer experience [13]. There is also reason to believe that finding benefit in a stressful experience could lead to improved immune function and health [15]; however, to the best of our knowledge, no studies have shown that a psychosocial intervention can enhance benefit finding in parallel with improving immune function. Immune function, including lymphocyte proliferation, may be associated with the course of breast cancer. Thus, it might be important if psychological interventions that improve psychological well-being also improve immune function among breast cancer patients. The study reported here tested the effects of a 10-week CBSM intervention on benefit finding and lymphocyte proliferation in response to specific activation of the T cell receptor, CD3, among early-stage breast cancer patients in the months after surgery and adjuvant therapy. We hypothesized that (a) women participating in CBSM would show increases in benefit finding over the intervention period, and (b) in vitro lymphocyte proliferation to anti-CD3 would increase among women in the CBSM condition 3 months after the intervention (about 6 months postsurgery), after potentially confounding adjuvant treatments were completed. Finally, we hypothesized that (c) increases in benefit finding during intervention would predict increases in lymphocyte proliferation 3 months later.

We investigated the impact of a 10-week, group-based CBSM intervention on proliferative response of PBMCs to specific activation of the T cell receptor, CD3, among women with early-stage breast cancer in the months after their diagnosis and treatment. As hypothesized, women in the CBSM group had significant increases in their lymphocyte proliferative response to anti-CD3 over the subsequent 3-month period while proliferative response decreased slightly among those in the comparison group. The increase in lymphocyte proliferation that we observed among the intervention participants was not accounted for by a change in distress. Possible explanations for this include the fact that the women in this study had early-stage breast cancer and, thus, a relatively good prognosis. Although breast cancer diagnosis is often associated with elevated distress [1], distress levels are often lower after surgery [1] and [13], as appears to be the case in the present study. This study also tended to self-select women who were getting along well enough with their treatment to be organized and motivated enough to attend weekly group meetings. Because the women entered the present study with relatively little overt emotional distress, there was little room for reduction in distress over the next 6 months. Women who took part in the CBSM intervention reported increases in benefit finding from having been diagnosed with breast cancer. The intervention was not designed with the intent of improving benefit finding; however, there are several components of the intervention that might have enhanced benefit finding. For example, cognitive restructuring taught in the sessions would lead to increases in positive reframing of situations. Coping skills training and assertiveness training taught in the sessions would lead to improved use of social support. Participation in the groups would foster emotional awareness and emotional expression among the group members. On a broader scale, the cancer trauma-related disruption in these women's lives could lead to reorganized cognitive schema that have benefits when compared with the person's precancer organization. All of the above are thought to lead to increases in perceived benefits from having had cancer and would be captured by the benefit finding scale used in this study. Changes in benefit finding from before to immediately after the 10-week intervention period predicted changes in lymphocyte proliferation at the 3-month follow-up, and this association was strongest among CBSM participants. How might changes in benefit finding influence immune function at a later time? It seems reasonable to suggest that CBSM participants in the present study now approach the stressors in their life with a new sense of strength and confidence, a greater connection to others, or a different sense of priorities—all elements of the benefit finding scale used in this study. Because of this, the women may now perceive potential stressors in their lives as a challenge rather than a threat. This fits with a theoretical model suggested by Eppel et al. [14], which suggests that working through stressful experiences can change a person's appraisal of subsequent stressors from a sense of threat to a sense of challenge. Perception of a potential stressor as a challenge may lead to positive physiological processes such as efficient allostasis, anabolic changes and, we purport, improved immune function. Perception of a potential stressor as a threat, in contrast, could lead to negative physiological processes such as allostatic load, catabolic processes and, we believe, poor immune function. In short, an individual who has experienced benefit finding is more resistant to future stressors. This resistance to future stressors could then lead to improved biological outcomes [14]. Another factor that might explain the change in proliferation associated with the intervention could be changes in neuroendocrine function, such as cortisol. High cortisol levels have been associated with poor immune function in a number of studies (for an overview, see Ref. [25]). This form of intervention has been shown to modulate neuroendocrine output (e.g., cortisol and catecholamines) in previous studies [26], [27], [28], [29] and [30]. One of these studies [29] was conducted as part of the same Antoni et al. [13] study from which the present study is drawn. Unfortunately, that study [29] was conducted with a different subset of women than the present study, and, thus, we were unable to test for cortisol as a mediator of the effects of the intervention on change in proliferation in the present study sample. The observed improvement in lymphocyte proliferative response could have important ramifications. While these results must be interpreted cautiously, there is evidence that poor in vitro lymphocyte proliferation is related to a worse prognosis among breast cancer patients [17], [18], [31] and [32]. In the Wiltschke [18] study, women whose proliferative response increased (mean increase=15.9%) were more likely to remain in remission over the next 2 years compared to women whose proliferative response decreased (mean decrease=26.5%; P<.001). In the present study, women in the CBSM condition experienced a 37% increase in their lymphocyte proliferation. In contrast, the mean proliferative response fell 12% among women in the comparison condition. An important limitation of this study was the sample size. Before definitive conclusions can be drawn, these findings must be replicated with a larger sample. Another limitation of this study was the restricted range of immune function assays conducted. It would have been interesting to measure natural killer (NK) cell function because of its association with breast cancer recurrence and disease progression [33]. There are some data to suggest that NK cell function can improve following stress management intervention [20]; however, a recent meta-analysis of psychological interventions and immune function found only mixed results [34]. Finally, these findings need to be interpreted in light of the fact that some women received chemotherapy between T1 and T3. Thus, the changes in proliferation observed may reflect how well the immune system has recovered from chemotherapy. If this is true, the CBSM intervention may be modulating immune system recovery from chemotherapy. In sum, CD3-induced lymphocyte proliferation plays a central role in the immune response cascade. These changes in proliferation as a result of the intervention are important and could predate improved health (e.g., increased resistance to infection) or, perhaps, decreased rates of cancer recurrence. While a number of studies suggest in vitro proliferation is associated with the course of breast cancer, these results must be interpreted with caution, as causality has not been determined. Future work will monitor these women over the next 5–10 years to determine if the psychological or immunological changes occurring after this intervention are related to health status or long-term disease-free survival.