© 1998 by Oxford University Press
Stress Reduction: Three Trials Test Its Impact on Breast Cancer Progression
Does psychological stress play a role in cancer progression and can reducing stress slow tumor growth? Some answers could be available soon after the year 2000 to this question, which has intrigued mental health specialists for several decades.
Up to now, the field of psychoneuroimmunology has yielded relatively little data related to cancer. In the area of infectious diseases, particularly colds, researchers have found a variety of links between psychological stress and the immune system. A few investigators have looked specifically at cancer patients and how the stress of diagnosis and treatment may affect immune response. Only a very few have ever designed an intervention to see whether stress reduction can improve immune function and slow cancer progression.
Now, three such studies are under way, all randomized, controlled trials of support-group interventions with breast cancer patients. None of the trials has data on tumor recurrence or survival yet. But early findings from one of them, reported on page 30, support the hypothesis that cancer-related stress is associated with cellular immune responses that may play a role in tumor growth.
Barbara Andersen, Ph.D., and colleagues at Ohio State University, Columbus, report that baseline measures of stress, specific to the diagnosis of cancer, were linked to levels of natural killer cell activity, T-cell responses, and other cellular responses "relevant to cancer prognosis."
It's still a big step from this finding to the question that Andersen would most like to answer: Can a stress reduction intervention influence cancer progression? But her larger study, plus two others now in progress in the United States and Canada, may help provide that answer over the next 6 years.
Andersen's larger study at Ohio State will involve 235 women with stage II or III breast cancer who are randomized, after surgery and before adjuvant therapy, into two groups, one of which will attend support groups for a year. The group sessions empasize both emotional support and education on, for instance, coping strategies.
All participants are assessed, first at enrollment and then 5 years following randomization to determine stress levels, cellular immune responses, and cancer recurrence. As of Dec. 1, 1997, 160 patients had been accrued. Recruitment should be completed in 1998, Andersen said, and results could be available in about 6 years.
While the step from reducing stress to reducing recurrence rates seems a giant one, the hypothesis has some evidence to back it. In the late 1980s, David Spiegel, M.D., a psychiatrist at Stanford University, discovered that breast cancer patients who received psychosocial support had better survival rates than patients in a control group who received no formal intervention.
Spiegel said he and his colleagues had set out to study the impact of a particular form of support on quality of life. They had not intended to look at survival. But after 10 years, they found that the 50 women in the support group (designed to encourage full "emotional expressiveness" about the cancer and allow patients to confront their feelings about the disease) had survival rates nearly twice those of the 36 patients in the control group. Mean survival for the intervention group was 36.6 months from the time of randomization compared with 18.9 months for the control group.
A few other small studies have had contradictory results. Most frequently cited is a randomized controlled trial at the University of California, Los Angeles, where Fawzy I. Fawzy, M.D., found that a psychosocial intervention was associated with longer survival in melanoma patients.
The other U.S. trial looking at stress reduction, immune factors, and cancer progression is under way at Stanford where Spiegel and colleagues are replicating the earlier study with a larger group. Initiated in 1990, the trial has 125 participants who were randomized into two groups, one of which attended support sessions.
Now about three-quarters of the way through a 10-year followup, the investigators are monitoring endocrine and cellular markers of immune function, such as cortisol levels and natural killer cell activity, as well as recurrence and survival rates. Spiegel said they expect to have some preliminary results published later this year, and final results, including survival data, could be ready around the year 2000.
A third trial on stress reduction and cancer progression is taking place in Canada at seven different sites. Led by Pamela Goodwin, M.D. at Mount Sinai Hospital, Toronto, the trial is replicating Speigel's intervention with 235 women. Goodwin said this study should have completed recruitment by the end of 1997 and that results, including survival data, could be available around 2000.
Controversy Continues
A major hypothesis in all three studies - that stress reduction can alter immune function in a way that influences cancer progression -- is a controversial one, said Sheldon Cohen, Ph.D. and Bruce Rabin, M.D., University of Pittsburgh, in their editorial on page 3. There is too little known, for one thing, about the type and magnitude of the immune responses that influence cancer progression, they say.
Another problem in studying the role of psychosocial interventions are the number and complexity of factors that might independently influence immune responses and cancer progression. All three trials now in progress are controlling for known prognostic factors, such as the extent of lymph node involvement and whether the tumor cells had estrogen receptors. But numerous other factors could play a role, including the immunosuppressive effects of cancer treatment, the details of which are not completely known.
Another point noted by Cohen and Rabin -- and one that turns up repeatedly in the literature on stress reduction and cancer survival - is that a support group could influence disease progression by means other than the stress reduction/immune response mechanism. For instance, supportive interventions might work because they encourage treatment compliance.
Spiegel said that he and colleagues examined this issue in their earlier study by reviewing participants' medical records. They found no difference in treatment that could account for the difference in survival rates. For that trial, "we've pretty much ruled out differences in treatment as an explanation," he said.
However, the impact of intervention on compliance with treatment is still an unknown. One hypothesis being tested in the Canadian study, said Goodwin, is that the psychosocial intervention improves survival by encouraging compliance. The Ohio State researchers are also looking at medical treatment, collecting data not only on prescribed treatment but also on the chemotherapy doses that each patient actually receives.
It is a key issue, Andersen said. "This is something we are looking at very closely."
-- Caroline McNeil
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