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Originally published as JCO Early Release 10.1200/JCO.2004.12.129 on September 27 2004 © 2004 American Society of Clinical Oncology. Effect of Cognitive-Existential Group Therapy on Survival in Early-Stage Breast CancerFrom the Memorial Sloan-Kettering Cancer Center, New York, NY; Departments of Medicine and Psychiatry, St Vincent's Hospital; The Peter MacCallum Cancer Institute; The University of Melbourne; and School of Psychology, La Trobe University, Melbourne; and Department of Psychological Medicine and Medical Oncology, Monash Medical Center and Monash University, Victoria, Australia Address reprint requests to David W. Kissane, MD, Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, 1242 Second Ave, New York, NY 10021; e-mail: kissaned{at}mskcc.org
PURPOSE: Cognitive-existential group therapy (CEGT) was developed to improve mood and mental attitude toward cancer in women with early-stage breast cancer receiving adjuvant chemotherapy. Given the debate about group therapy's association with increased survival in women with metastatic breast cancer, we were curious to check its effect at a much earlier stage in the cancer journey. PATIENTS AND METHODS: We randomly assigned 303 women with early-stage breast cancer who were receiving adjuvant chemotherapy to either 20 sessions of weekly group therapy plus three relaxation classes (n = 154) or to a control condition of three relaxation classes alone (n = 149). The primary outcome was survival. RESULTS: CEGT did not extend survival; the median survival time was 81.9 months (95% CI, 64.8 to 99.0 months) in the group-therapy women and 85.5 months (95% CI, 67.5 to 103.6 months) in the control arm. The hazard ratio for death was 1.35 (95% CI, 0.76 to 2.39; P = .31). In contrast, histology and axillary lymph node status were significant predictors of survival. Low-grade histology yielded a hazard ratio of 0.342 (95% CI, 0.17 to 0.69), and axillary lymph node–negative status yielded a hazard ratio of 0.397 (95% CI, 0.20 to 0.78). CONCLUSION: CEGT does not prolong survival in women with early-stage breast cancer.
Since the report by Spiegel1 stating that group therapy extends survival in women with metastatic breast cancer, nine other studies have yielded mixed results, with the recent Canadian multisite trial failing to replicate the original findings.2 The focus throughout has been on an advanced stage of cancer. In women with early-stage breast cancer, helplessness and/or hopelessness and depression have been negatively linked with survival, whereas factors proposed as relevant to survival (eg, fighting spirit and the cancer-prone personality) have not been confirmed as exerting an influence.3 Resistance to progression of cancer could be mediated through enhancement of coping strategies, improved adherence to anticancer treatment overall, the salutary effect of social support, and the endocrine, immune, and autonomic nervous systems.4 Given this state of knowledge, a prospective trial of the impact of group therapy at a much earlier stage of breast cancer seemed warranted. We devised cognitive-existential group therapy (CEGT) for women receiving adjuvant chemotherapy with the goals of promoting active coping and mutual support.5 CEGT has a beneficial effect on mood and family relationships.6 In this brief report, we focus on the impact of CEGT on survival in women with early-stage disease.
Design Patients were recruited between August 1994 and February 1997 from the oncology departments of nine metropolitan hospitals in Melbourne, Australia. Ethics committee approval was obtained from each institution. All patients gave informed consent for the trial of treatment and associated study of survival. Eligibility criteria were age under 65 years (lest the biology of the disease differed in older age groups), a histologically confirmed diagnosis of stage II breast cancer or stage I cancer judged by the treating medical oncologist to need adjuvant chemotherapy, adequate use of English, and geographic accessibility. Exclusion criteria were prior history of cancer (other than nonmelanocytic skin cancer), psychotic illness, dementia, and intellectual disability. Staging was confirmed by review of operative notes and reports of tumor size, histology, axillary lymph node involvement, hormone receptor status, hemoglobin, leukocytes and blood film, electrolytes and urea, calcium, liver function, chest x-ray, and bone scan. All patients received the standard treatments offered for their clinical circumstances by their oncologists. A sample of 150 women in each condition was based on consideration of the survival analysis using the method of Akazawa et al,7 permitting recognition of a 15% difference in survival over 5 years with a 0.05 level of significance, a power of 80%, a study duration of 5 years, and a hazard ratio of 2:1 comparing control to treatment. Women in the intervention groups attended 20 weekly sessions lasting 90 minutes. Each group comprised six to eight patients and two therapists (one always a woman) drawn from the disciplines of consultation-liaison psychiatry, psychology, social work, and oncology nursing. The therapy was manualized and had the six goals of promoting a supportive environment, facilitating grief, reframing negative thinking, enhancing coping and problem solving, fostering hope, and setting priorities for the future.5 We prepared patients individually in a standardized way to minimize dropouts. Groups typically began with patients sharing their experience of illness, followed by a joint focus on grief and existential concerns. Cognitive aspects were integrated during the middle phase. Typical themes included anxiety about dying and fear of the cancer recurring; facing uncertainty; understanding anticancer treatments; the doctor-patient relationship; body and self-image; sexuality; surgical reconstruction; relating to partner, friends, and family; lifestyle; and goals for the future. Relaxation classes followed in sessions 10 to 12. The women were encouraged to exchange phone numbers and to meet informally (eg, over refreshments after each session) to reinforce the support gained in the therapy sessions. Fifteen therapists were trained in a series of workshops and co-led a pilot group to maximize their familiarity with the model. Therapists were supervised weekly by a chief investigator; they presented detailed process notes about the previous session and were encouraged to adhere to the set guidelines. Supervisors maintained a checklist for each group to ensure that themes were addressed adequately or otherwise revisited.6 In the relaxation classes, women were taught progressive muscle relaxation with guided imagery; the technique was standardized through use of a therapist's manual. A relaxation tape was issued to all participants for continued use at home. The classes were designed to minimize interaction. All relaxation classes, whether they were a supplementary program to CEGT or given to serve as the control condition, were led by the same occupational therapist.
Randomization
Masking and Follow-Up Trained research assistants conducted baseline and follow-up assessments, which were performed at 6, 12, 18, and 24 months. Details of any off-study psychological help were sought. A different research assistant, who was blinded to randomization, reviewed patients' medical records at 3 and 5 years after recruitment. She completed a detailed protocol about the patients' disease status, results of investigations, and dates of confirmed recurrence or death.
Statistical Analysis Kaplan-Meier survival analyses were constructed using the log value. Univariate and multivariate Cox proportional hazards models were used to determine effects on survival. The multivariate Cox models included factors that differed between groups at baseline and well-known tumor prognostic factors and explored time to death.
Demographic and Clinical Features Three hundred three (62%) of 491 eligible women were enrolled; 154 were assigned to CEGT, and 149 were assigned to the control arm. Figure 1 shows the design with numbers of patients at each stage. Reasons for refusal included being too busy, coping, wanting to move on, and not being a group person. The sociodemographic profile and clinical data have been described elsewhere.6 Most women were middle aged (mean age ± standard deviation, 46.3 ± 8.2 years), married (76%), Australian born (73%), and educated to senior high school or beyond (70%). Half of the women were working (48%), and of these, 53% were in professional jobs. Sociodemographic variables by randomization arm are listed in Table 1. Clinical variables by randomization arm are listed in Table 2.
Most women (83%) had stage II breast cancer; 87 (29%) had more than three axillary lymph nodes involved, suggesting a higher risk of recurrence. Conservative breast surgery was undertaken in 164 women (54%); and mastectomy was performed in 139 women (46%). One hundred seventy-four women (57%) received radiotherapy, and 287 women (95%) received chemotherapy. A cyclophosphamide, methotrexate, and fluorouracil regimen was administered to 202 women (67%), and a doxorubicin and cyclophosphamide regimen was administered to 85 women (28%). Hormone therapy was added later in 145 women (48%). Baseline interviews occurred a median of 92 days (mean ± standard deviation, 102 ± 56 days) after surgery. The therapy and control arms were similar sociodemographically and also with respect to clinical aspects of the cancer and its treatment.
Psychosocial Outcome of Therapy
Survival
To explore the relationships between key variables and survival, 11 dichotomized covariates were fully modeled in a multivariate Cox regression analysis. These were receiving group therapy, tumor histology grade 1 or 2, lymph node status, tumor size of less than 20 mm, stage I breast cancer, estrogen receptor-positive, progesterone receptor-negative, adjuvant chemotherapy, adjuvant hormone therapy, radiotherapy, and diagnosis of depression at commencement of group therapy. The resulting change in the –2 log likelihood coefficient was significant (11 variables,  2 = 26.02, P = .006). In most instances, however, the beta coefficient was small and nonsignificant. Notably, neither having a diagnosis of depression nor receiving group therapy contributed significantly to the equation.
The three variables making the largest contributions (histology, node status, and tumor size) were entered into a subsequent Cox regression analysis. The –2 log likelihood change was significant (three variables,
Other variables entered into multivariate models were education, age, and hospital site, none of which were significant. The effects of CEGT remained nonsignificant after adjustment for each of these variables.
The use of CEGT in the context of early-stage breast cancer did not prolong survival. Despite group therapy reducing anxiety and sustaining family relationships,6 no beneficial effects with respect to survival were demonstrable. These findings are consistent with those of Goodwin et al,2 Cunningham et al,8 and Edelman et al9 for women with advanced breast cancer, generating a series of studies that suggest that psychosocial interventions are not able to prolong survival. In contrast, tumor histology and axillary lymph node status, two well-recognized prognostic factors for breast cancer, were significant predictors of survival in this study. Because all patients were receiving adjuvant chemotherapy, a behavioral impact on adherence to such treatment, as demonstrated in the study by Richardson et al,10 is unlikely with this design. We must conclude that a direct effect of an adjuvant psychological therapy like CEGT on survival has not been substantiated. This should not detract from its benefits in promoting adjustment in patients who are at risk of psychosocial distress. Indeed, we concur with Goodwin's recent advocacy for professionally led group therapy to be more widely available for women with breast cancer.11 Methodologic debates will continue in this field, with each design being subject to criticism. We offered relaxation therapy to both arms but yet sustained a classroom effect in the control arm to ensure that it did not inadvertently generate support. Nevertheless, we sought to ensure that the women were not demoralized by randomization to a no-treatment condition. Qualitative data reported in the original outcome publication of our study confirmed that there was a significant difference between the two arms in their sense of feeling supported.6 The CEGT women achieved a very significant cohesiveness, knowing that group members understood their plight and shared their treatment experience. These women have continued to meet regularly several years after CEGT. We express confidence in the quality and sustained nature of the group support engendered, but note the absence of any impact on survival. Negative studies often pass unreported, but this brief report is the first survival study of group therapy in women with early-stage breast cancer and, as such, represents a noteworthy contribution to what has been an earnestly debated issue.
The authors indicated no potential conflicts of interest.
Supported by the Research and Development Grants Advisory Committee of the Australian Commonwealth Department of Health and Human Services, the National Health and Medical Research Council of Australia, and the Pratt Foundation. Authors' disclosures of potential conflicts of interest are found at the end of this article.
1. Spiegel D: Effects of psychotherapy on cancer survival. Nat Rev Cancer 2:383-389, 2002[CrossRef][Medline]
2. Goodwin PJ, Leszcz M, Ennis M, et al: The effect of group psychosocial support on survival in metastatic breast cancer. N Engl J Med 345:1719-1726, 2001 3. Watson M, Haviland JS, Greer S, et al: Influence of psychological response on survival in breast cancer: A population-based cohort study. Lancet 354:1331-1336, 1999[CrossRef][Medline] 4. Spiegel D, Classen C: Group Therapy for Cancer Patients: A Research-Based Handbook of Psychosocial Care. New York, NY, Basic Books, 2000, pp 42-54 5. Kissane DW, Bloch S, Miach P, et al: Cognitive-existential group therapy for patients with primary breast cancer: Techniques and themes. Psychooncology 6:25-33, 1997[CrossRef][Medline] 6. Kissane DW, Bloch S, Smith GC, et al: Cognitive-existential group psychotherapy for women with primary breast cancer: A randomized controlled trial. Psychooncology 12:532-546, 2003[CrossRef][Medline] 7. Akazawa K, Nakamura T, Moriguchi S, et al: Simulation program for estimating statistical power of Cox's proportional hazards model assuming no specific distribution for the survival curve. Comput Methods Programs Biomed 35:203-212, 1991[CrossRef][Medline] 8. Cunningham AJ, Edmonda CV, Jenkins GP, et al: A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer. Psychooncology 7:508-517, 1998[CrossRef][Medline] 9. Edelman S, Bell DR, Kidman AD: A group cognitive behaviour therapy programme with metastatic breast cancer patients. Psychooncology 8:295-305, 1999[CrossRef][Medline] 10. Richardson JL, Shelton Dr, Krailo M, et al: The effect of compliance with treatment on survival among patients with hematologic malignancies. J Clin Oncol 8:356-364, 1990[Abstract] 11. Goodwin PJ: Psychosocial support for woman with advanced breast cancer. Breast Cancer Res Treat 81:S103-S110, 2003 (suppl 1)[CrossRef] Submitted December 18, 2003; accepted May 14, 2004.
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
three nodes), hormone receptor status (positive v negative), and tumor size (
2 cm v < 2 cm). Patients were assigned in a 1:1 ratio to either CEGT plus three relaxation classes or three relaxation classes alone (see trial flow diagram, 
