The present trial is part of the ongoing effort to test for changes in biobehavioral outcomes and disease end points after a psychological intervention. Lowering stress is the main goal for interventions,1,2
and the most successful interventions reduce patients’ anxiety.38,39
When untreated, anxieties are common and arise from many sources,40
and cancer symptoms.47,48
Here, anxiety was significantly reduced in the intervention arm. Analyses also contrasted patients who differed in the magnitude of cancer-specific stress. For women with high stress, the intervention provided a 36% reduction in total mood disturbance compared with the 12% reduction found for the assessment arm. Parallel effects emerged for feelings of fatigue. This may be important because fatigue can affect every aspect of a patient’s life,49
yet it is often not recognized. Oncologists attest that pain, for example, is routinely treated (95%), whereas fatigue receives little to no attention (5%).50
Many, if not all, interventions attempt to provide social support to patients, but it is rare that specific therapeutic techniques are used to improve a patient’s social adjustment in the real world to enable or facilitate social support from specific others.1,2
We are aware of only four intervention studies that have noted strategies to help patients to use social support,18
enhance interpersonal relationships,51
or address relationship difficulties.52,53
In two other studies, patients were encouraged to return to prior social activities and maintain relationships.54,55
Even so, studies have not included social adjustment or social support from others as an intervention outcome1,2
as was done here.
The patients’ initial assessment occurred shortly after illness onset and early treatment because it was regarded as providing a more realistic reflection of how a patient’s family and friends actually respond in a crisis.56
The group format may have provided, in general, social support, but more importantly, the intervention components helped patients to make their established network of relationships function more effectively for them. Maintaining existing relationships is important because data indicate that quality of life is poorer for breast cancer patients who are socially isolated.57
We do not know if the intervention patients actually received or only perceived more support from their family. When compared, it is perceived support that may actually be more important for adjustment58–60
and health effects.12
Some interventions with cancer patients focus only on dietary,61–64
or smoking cessation change.67,68
The intervention model for these studies has been to have a professional (eg, dietician) meet with a patient for one to several sessions. To our knowledge, psychological interventions for cancer patients have not previously included health behaviors as intervention targets or outcomes. The single exception offered skin protection information to melanoma patients receiving a psychoeducational intervention.69
Despite the brevity of the health behavior component (four of 18 sessions), significant changes in both positive and negative behaviors occurred. The dietary sessions provided information, sampling of low-fat snacks, food intake diaries, and other components. Reductions in fat intake were readily achieved, which was consistent with lengthier dietary interventions.25,61,62
There were no differential changes in activity or exercise, likely because of the minimal time spent. However, even large randomized trials offering lengthy exercise interventions (eg, 26 weeks) have reported significant change on some measures but not on others.66
Finally, the smoking reductions in the intervention arm were significant, despite the low number of smokers in the trial. Recent research indicates that individuals who continue to smoke after a cancer diagnosis endorse reasons such as “I am more relaxed when I smoke” and “smoking relieves tension”.70
Our intervention was focused on stress reduction, and the specific recommendations for smoking cessation were similar to those in the National Cancer Institute’s 4 A’s program used by physicians (ie, Ask, Advise to quit, Assist the patient to stop, and Arrange follow-up monitoring),71
which has been effective in increasing cessation rates.72,73
Poor adherence to treatment is a behavioral problem and one that has received minimal investigation despite its importance.74
Within the assessment group, there was a greater dispersion of chemotherapy dosages, more premature terminations of treatment, and more lost to follow-up cases. The data are consistent and in the predicted direction. However, in future research, a larger sample size and disease sites yielding more variability in dose-intensity values and/or higher rates of nonadherence are needed.
Finally, the often-proposed mechanism for survival effects is improved emotions and/or lowered stress modulating the immune system, which, in turn, alters disease progression. Several intervention studies have tested for changes in NK cell lysis, and, with one exception,75
null effects have been reported.76–80
We too observed no change in NK cell lysis, but we found significant, reliable effects with blastogenesis; a pattern that has been reported by others.81
Blastogenesis remained stable or increased across time for intervention patients, whereas responses declined for assessment patients. These experimental data extend our correlational report showing a negative relationship between high stress and low immune responses as women entered the trial.32
It is notable that the intervention effects on blastogenesis were reliable within and across the Con A and PHA assays. Even so, some might suggest that these intervention effects could be explained by other factors. We do not believe this is the case, which is a viewpoint bolstered by the successful randomization equating the groups, the reliability of blastogenesis findings, and the predicted consistency of the blastogenesis findings with the psychological and behavioral changes.
We also tested competing explanations for the intervention effect on immunity, testing for effects caused by cell counts, chemotherapy, or radiation. When CD3, CD4, and CD8 cell counts were statistically controlled in MANCOVAs, study arm effects remained (all P < .05). Thus, the changes in blastogenesis were functional and not a result of cell trafficking. Regarding chemotherapy, patients from both study arms were equally likely to have completed chemotherapy at 4 months, and the study arms did not differ significantly in the number of patients receiving chemotherapy () or the dosages prescribed (; all P > .05). Nevertheless, MANCOVAs controlling for the types of chemotherapy received (eg, doxorubicin and paclitaxel) were conducted. They showed the same positive intervention effects on both Con A and PHA (all P < .05). Regarding radiation, the study arms did not differ significantly in the number of patients receiving this treatment. By 4 months, more patients in the intervention arm (n = 25) were still receiving radiation compared with the assessment arm (n = 9; P = .005). When radiation status was controlled, however, the positive effect of the intervention on PHA and Con A blastogenesis remained. Taken together, these analyses rule out competing explanations and provide evidence for a robust effect of the intervention on T-cell blastogenesis.
The immune changes observed in the assessment arm (ie, reduced proliferation in response to T-cell mitogens) may indicate the presence of a functional defect in T-cell immunity, although the precise immune implications of this phenomena cannot be discerned at this point in the study. Indeed, it is possible that the observed alterations in lectin-induced blastogenesis do not represent a distinct immune deficiency. Any reduction in T-cell effector function might theoretically lead to increased rates of breast cancer recurrence in surgically treated stage II and III breast cancer patients because of the role the T cells seem to play in the process of tumor surveillance.82
However, it is important to note that alterations in polyclonal T-cell proliferation in response to ex vivo stimulation of patient peripheral-blood mononuclear cells with Con A or PHA are of uncertain significance with respect to subsequent cancer progression. Our follow-up of the study participants will continue, and we will be better able to determine whether these immune effects or others are related to breast cancer recurrence rates.
If psychological interventions impact cancer survival, the process is likely to be multifactorial, including psychological factors, behavioral factors, biologic responses, and other factors.16
This trial includes tests for the expected reductions in emotional distress plus the additional intervention targets (health behaviors, adherence, and immunity), which may represent plausible routes to improved survival. In previous trials, the intervention effects have been strong,10,52,69,75,83–86
It is important to note that positive intervention effects are a necessary condition for testing for recurrence or survival effects. In this study, the predicted effects for emotional distress, social support, health behaviors, and immunity were observed, with some effects being stronger than others. In combination, they provide the context for a meaningful test of disease end point hypotheses and a strategy to examine multiple routes by which psychological interventions may affect disease course.