VOLUME 22 䡠 NUMBER 21 䡠 NOVEMBER 1 2004

JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T

Effect of Cognitive-Existential Group Therapy on

From the Memorial Sloan-Kettering
Cancer Center, New York, NY; Depart-
ments 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 Psycho-
logical Medicine and Medical Oncology,
Monash Medical Center and Monash
University, Victoria, Australia.
Submitted December 18, 2003; accepted
May 14, 2004.
Supported by the Research and Devel-
opment Grants Advisory Committee of
the Australian Commonwealth Depart-
ment of Health and Human Services,
the National Health and Medical
Research Council of Australia, and the
Pratt Foundation.
Authors’ disclosures of potential con-
flicts of interest are found at the end of
this article.
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@mskcc.org.
Survival in Early-Stage Breast Cancer
David W. Kissane, Anthony Love, Allison Hatton, Sidney Bloch, Graeme Smith, David M. Clarke,
Patricia Miach, Jill Ikin, Nadia Ranieri, and Raymond D. Snyder
A B S T R A C T
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 chemo-
therapy. 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.
J Clin Oncol 22:4255-4260. © 2004 by American Society of Clinical Oncology

© 2004 by American Society of Clinical confirmed as exerting an influence.3 Resis-

Oncology INTRODUCTION
0732-183X/04/2221-4255/$20.00
Since the report by Spiegel1 stating that
DOI: 10.1200/JCO.2004.12.129
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
tance to progression of cancer could be me-
diated through enhancement of coping
strategies, improved adherence to antican-
cer treatment overall, the salutary effect of
social support, and the endocrine, immune,
and autonomic nervous systems.4
Given this state of knowledge, a pro-
spective 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

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 Kissane et al
this brief report, we focus on the impact of CEGT on sur-
vival in women with early-stage disease.
PATIENTS AND METHODS
Design
Patients were recruited between August 1994 and February
1997 from the oncology departments of nine metropolitan hospi-
tals in Melbourne, Australia. Ethics committee approval was ob-
tained 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, ade-
quate use of English, and geographic accessibility. Exclusion crite-
ria 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, electro-
lytes 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 com-
paring control to treatment.
Women in the intervention groups attended 20 weekly ses-
sions lasting 90 minutes. Each group comprised six to eight pa-
tients 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 cop-
ing and problem solving, fostering hope, and setting priorities
for the future.5 We prepared patients individually in a stan-
dardized way to minimize dropouts.
Groups typically began with patients sharing their experience
of illness, followed by a joint focus on grief and existential con-
cerns. Cognitive aspects were integrated during the middle phase.
Typical themes included anxiety about dying and fear of the cancer
recurring; facing uncertainty; understanding anticancer treat-
ments; the doctor-patient relationship; body and self-image; sex-
uality; surgical reconstruction; relating to partner, friends, and
family; lifestyle; and goals for the future. Relaxation classes fol-
lowed in sessions 10 to 12. The women were encouraged to ex-
change 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 main-
tained a checklist for each group to ensure that themes were
addressed adequately or otherwise revisited.6
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In the relaxation classes, women were taught progressive
muscle relaxation with guided imagery; the technique was stan-
dardized 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
Randomization was independently performed using a
computer-generated schedule, stratified on nodal status (⬎ three
positive nodes v ⱕ three nodes), hormone receptor status (positive
v negative), and tumor size (ⱖ 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, Fig 1).
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 random-
ization, 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
An intent-to-treat approach was used in all analyses. Data
were analyzed using SPSS (1999; SPSS, Inc, Chicago, IL), StatXact
(1999; Cytel, Cambridge, MA), EGRET for Windows 2.0.1 (1999;
Cytel), and SPLUS-2000 (1999; Insightful Corp, Seattle, WA). The
Fisher’s exact test for dichotomous variables, Pearson ␹2 test for
contingency tables for nonordinal categoric data, Cochran-
Armitage test for trend for ordinal data, and two-tailed t tests for
continuous variables were applied to compare the group and
control arms at baseline.
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 multivar-
iate Cox models included factors that differed between groups at
baseline and well-known tumor prognostic factors and explored
time to death.
RESULTS
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 edu-
cated to senior high school or beyond (70%). Half of the
women were working (48%), and of these, 53% were in pro-
fessional jobs. Sociodemographic variables by randomization
JOURNAL OF CLINICAL ONCOLOGY
 Group Support and Survival

Fig 1. Trial profile outlining randomized controlled trial design with numbers of patients at each stage.
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 Kissane et al

arm are listed in Table 1. Clinical variables by randomization

Table 2. Clinical Variables by Randomization Arm
arm are listed in Table 2.
Group Control
Most women (83%) had stage II breast cancer; 87 (n ⫽ 154) (n ⫽ 149)
(29%) had more than three axillary lymph nodes involved, Factor No. % No. %
suggesting a higher risk of recurrence. Conservative breast
Family history of breast
surgery was undertaken in 164 women (54%); and mastec- cancer
tomy was performed in 139 women (46%). One hundred Yes 62 40 55 37
seventy-four women (57%) received radiotherapy, and 287 No 92 60 94 63
women (95%) received chemotherapy. A cyclophospha- Family history of other
cancer types
mide, methotrexate, and fluorouracil regimen was admin- Yes 109 71 100 68
istered to 202 women (67%), and a doxorubicin and No 45 29 48 32
cyclophosphamide regimen was administered to 85 women Unknown — — 1 —
(28%). Hormone therapy was added later in 145 women Nulliparous
Yes 32 21 21 14
(48%). Baseline interviews occurred a median of 92 days
No 122 79 128 86
(mean ⫾ standard deviation, 102 ⫾ 56 days) after surgery. Stage of breast cancer
The therapy and control arms were similar sociodemo- I 18 12 31 21
graphically and also with respect to clinical aspects of the II 136 88 118 79
cancer and its treatment. Tumor size, mm
Mean 22.2 21.6
Psychosocial Outcome of Therapy Median 20 20
As previously reported and summarized here to pro- Standard deviation 9.5 9.0
Range 5-50 5-45
vide a context for the survival analysis, women receiving
ⱕ 10 mm 11 7 11 8
group therapy were shown to have reduced anxiety 11-20 mm 72 47 65 44
21-30 mm 47 31 53 36
31-40 mm 19 12 14 10
41-50 mm 5 3 4 3
Table 1. Sociodemographic Variables by Randomization Arm Unknown — — 2 —
Histologic grade
Group Control
1 7 5 11 8
(n ⫽ 154) (n ⫽ 149)
2 59 42 54 39
Factor No. % No. % 3 75 54 74 53
Age Unknown 13 — 10 —
Mean 45.4 47.3 Estrogen receptor status
Median 45 47 Positive 94 63 90 64
Standard deviation 8.0 8.3 Negative 56 37 51 36
Range 26-64 26-65 Unknown 4 — 8 —
Marital status Progesterone receptor
Married 112 73 117 79 status
Separated 2 1 5 3 Positive 108 73 104 74
Divorced 15 10 16 11 Negative 40 27 37 26
Widowed 7 5 3 2 Unknown 6 — 8 —
Single 18 12 8 5
Education, highest level
Primary 0 0 2 1
Year 6-10 40 26 51 34
Year 11-12 43 28 47 32 (P ⫽ .05, two-sided) and a trend towards improved family
Tertiary 71 46 49 33 functioning compared with controls (P ⫽ .07, two-sided).
Occupation
The women in the groups reported greater satisfaction with
Professional 90 58 71 48
Clerical 48 31 57 38
their therapy (P ⬍ .001, two-sided), appreciating the sup-
Semiskilled 15 10 14 9 port and citing better coping, self-growth, and increased
Unskilled 1 1 7 5 knowledge about cancer and its treatment. They valued the
Current employment CEGT therapy. Overall effect size for the group intervention
Working 74 48 72 48
was small (d ⫽ 0.25), with cancer recurrence having a
Home duties 35 23 33 22
Unemployed 4 3 5 3
deleterious effect in three of the 19 therapy groups. Psychol-
Retired 11 7 19 13 ogists as a discipline, however, achieved a moderate mean
Disabled 30 20 19 13 effect size (d ⫽ 0.52). We concluded that CEGT is a useful
Student 0 0 1 1 adjuvant psychological therapy for women with early-stage
breast cancer. Group-as-a-whole effects are powerful, but

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 Group Support and Survival
Fig 2. Kaplan-Meier survival curves for women assigned to cognitive-
existential group therapy (CEGT) and control conditions. There were no
significant differences between CEGT groups and control conditions.
the training and experience of the therapist is especially
critical to an efficacious outcome.
Survival
The Kaplan-Meier analysis revealed a median survival
of 81.9 months (95% CI, 64.8 to 99.0 months) in the CEGT
group compared with 85.5 months (95% CI, 67.5 to 103.6
months) in the control arm (Fig 2). According to the uni-
variate Cox model, the hazard ratio for death in the CEGT
arm compared with the control arm was 1.35 (95% CI, 0.76
to 2.39; P ⫽ .31). A multivariate Cox model identified no
significant effect of CEGT on survival (hazard ratio, 1.37;
95% CI, 0.73 to 2.32; P ⫽ .37).
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, radio-
therapy, and diagnosis of depression at commencement of
group therapy. The resulting change in the ⫺2 log likeli-
hood 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 con-
tributed significantly to the equation.
Table 3. Final Multivariate Cox Regression Analysis Model of Predictors of Survival
Variable Beta Coefficient
Tumor histology grade 1 or 2 ⫺1.074
Node negative ⫺0.923
Tumor size ⬍ 20 mm ⫺0.455
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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, ␹2 ⫽ 22.135,
P ⫽ .000). Two of the three variables were significantly
associated with survival; details of these variables, including
their coefficients and hazard ratios, are listed in Table 3.
Patients with favorable histology and negative axillary
nodes were likely to survive longer.
Other variables entered into multivariate models were
education, age, and hospital site, none of which were signif-
icant. The effects of CEGT remained nonsignificant after
adjustment for each of these variables.
DISCUSSION
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 pro-
long 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 chemo-
therapy, a behavioral impact on adherence to such treat-
ment, 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 profes-
sionally 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
Hazard 95% CI for
P Ratio Hazard Ratio
.003 0.342 0.169 to 0.692
.007 0.397 0.202 to 0.781
.128 0.635 0.353 to 1.140
4259
 Kissane et al

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 orig-
inal 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 treat-
ment experience. These women have continued to meet
regularly several years after CEGT. We express confi-
dence 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 ther-
apy in women with early-stage breast cancer and, as such,
represents a noteworthy contribution to what has been
an earnestly debated issue.
■ ■ ■
Authors’ Disclosures of Potential
Conflicts of Interest
The authors indicated no potential conflicts of interest.

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