Available online at www.sciencedirect.

com

Cognitive and Behavioral Practice 16 (2009) 253–265

www.elsevier.com/locate/cabp

Biobehavioral Intervention for Cancer Stress:

Conceptualization, Components, and Intervention Strategies
Barbara L. Andersen, Department of Psychology, Comprehensive Cancer Center and Solove Research Institute,
The Ohio State University
Deanna M. Golden-Kreutz, Department of Internal Medicine, The Ohio State University
Charles F. Emery, Department of Psychology, Comprehensive Cancer Center and Solove Research Institute,
The Ohio State University
Debora L. Thiel, Madigan Army Medical Center, Nisqually Family Medical Center, Fort Lewis, Washington

Trials testing the efficacy of psychological interventions for cancer patients had their beginnings in the 1970s. Since then, hundreds of
trials have found interventions to be generally efficacious. In this article, we describe an intervention grounded in a conceptual model
that includes psychological, behavioral, and biological components. It is from this biobehavioral view that an intervention was
developed and tested among newly diagnosed cancer patients. It was found efficacious for biobehavioral outcomes, health, and disease
endpoints. Here we provide investigators and clinicians with an elaborated description of the components and strategies to aid in
replication and dissemination.

I N 1994 we offered a conceptualization for under-

standing the relationship between the stress of cancer
diagnosis and treatment and subsequent disease progres-
sion. A randomized clinical trial (RCT), called the Stress
and Immunity Breast Cancer Project (SIBCP), was
designed to test the hypothesis that patients receiving a
psychological intervention designed to target stress and
relevant behaviors would show improved survival com-
pared to patients who received usual care. Consecutive
cases of patients (N = 227) newly diagnosed with regional
(Stage II or II) breast cancer were accrued from a
National Cancer Institute comprehensive cancer hospital.
All had received surgical treatment and were accrued
prior to beginning adjuvant therapy (radiation and/or
chemotherapy) and randomized to intervention-plus-
assessment or assessment-only study arms. The endpoints
were reduction in risk for recurrence and breast cancer
death. Previously reported, the intervention produced
significant gains across secondary outcomes [distress,
social adjustment, health behaviors (diet, smoking cessa-
tion), treatment adherence, health] and also enhanced T
cell immunity (Andersen, Farrar et al., 2007; Andersen
et al., 2004). After a mean of 11 years of follow-up,
intervention patients had a reduced risk of disease pro-
1077-7229/09/253–265$1.00/0
© 2009 Association for Behavioral and Cognitive Therapies.
Published by Elsevier Ltd. All rights reserved.
gression, i.e., breast cancer recurrence [Hazard Ratio
(HR) = 0.55, P = .034] and death from breast cancer
(HR = 0.44, P = .016; Andersen et al., 2008).
To facilitate understanding, replication, and dissemi-
nation, we provide intervention detail. We begin with an
overview of the conceptual model as originally described
(Andersen, Kiecolt-Glaser, & Glaser, 1994) and subse-
quently empirically supported. This introduction outlines
the constructs that informed the development of the
intervention and specification of the intervention targets
and outcomes.
Biobehavioral Model of Cancer Stress and
Disease Course
Psychological Pathways
Our conceptualization begins, not surprisingly, with
the view that severe, acute stress occurs at the time of
cancer diagnosis (see Figure 1). The acute distress accom-
panying diagnosis can, in turn, contribute to a stable,
lower quality of life for cancer patients, and trial data
supported this hypothesis (Golden-Kreutz & Andersen,
2004; Golden-Kreutz et al., 2005). Moreover, patients who
cope poorly at the time of diagnosis report lower meaning
in life in the year following the end of cancer treatments
(Jim et al., 2006).
After the initial shock, patients anxiously anticipate the
beginning of difficult cancer therapies; for the majority,
treatment is multimodal. Many studies have focused on
254 Andersen et al.
Figure 1. The biobehavioral model of cancer stress and disease course (adapted from Figure 1 in Andersen, B.L., Kiecolt-Glaser, J.K., and
Glaser, R. (1994). A biobehavioral model of cancer stress and disease course. American Psychologist, 49, 389-404). Used with permission.
alleviating the fears surrounding chemotherapy, including
conditioned reactions (e.g., anticipatory nausea and vomit-
ing; Redd, Montgomery, & DuHamel, 2001). Emotional
distress may linger long after treatment has ended. For
example, mid way through our trial taxane chemo-
therapies were introduced and added onto standard
regimens (e.g., Adriamycin plus Cytoxan). As others had
found (Fountzilas et al., 2005), patients receiving taxanes
experienced significantly higher rates of selected toxicities,
including arthralgia/myalgia (45% vs. 26%) and ataxia
(20% vs. 5%). However, unexpected was the finding that
those receiving the taxanes had significantly worse emo-
tional distress and quality of life throughout treatment.
Emotional recovery for taxane patients required 2 years,
on average, versus 6 to 12 months for nontaxane patients.
Thus, cancer treatments can confer risk for psychological
distress of long duration (Thornton et al., 2008).
There are many other examples of psychological and
behavioral changes in the months following diagnosis and
into the early survivorship years. Cancer treatments have
the potential to impact intimate relationships, as we
(Yurek, Farrar, & Andersen, 2000) and others (Kornblith
& Ligibel, 2003) have found. Cancer can bring financial
strain (Arndt et al., 2004). Treatment or recovery can
disrupt one's employment, including job loss for some
(Bradley et al., 2005). One fifth of cancer survivors report
these difficulties (Hewitt, Breen, & Devesa, 1999).
Residual poor mental health may also contribute to job
strain, as we found that continuing cancer-specific stress
covaried with employment absenteeism for a subset of
patients from the trial who were subsequently found to
have diagnosed or subsyndromal posttraumatic stress
disorder (PTSD; Shelby et al., 2008).
Biological Pathways
Stress triggers important biological effects involving
the autonomic, endocrine, and immune systems. Stress
may be routed to the immune system by the central
nervous system (CNS) via activation of the sympathetic
nervous system or through neuroendocrine-immune
pathways (i.e., the release of steroid hormones, gluco-
corticoids). Stress-related changes in neuroendocrine
function have been documented in studies of the
hypothalamic-pituitary-adrenal (HPA) axis. Cancer
patients may exhibit dysregulation of the HPA axis similar
to that observed in depressed patients without cancer
(i.e., hypersecretion of ACTH and cortisol, adrenal and
pituitary hypertrophy; Lundstrom & Furst, 2003; Raison
& Miller, 2001) or show blunted ACTH and cortisol
diurnal variation in response to acute stress (Bower,
Ganz, & Aziz, 2005; Giese-Davis et al., 2004; Mazzoccoli
et al., 2005). Also, hormones released under stress (e.g.,
catecholamines, cortisol, prolactin, and growth hor-
mone) have been implicated in immune modulation
(Bergmann & Sautner, 2002; Rontgen et al., 2004).
Lymphocytes, monocytes/macrophages, and granulo-
cytes possess receptors for neurotransmitters that are
capable of immune regulation (Engler et al., 2004; Kohm
& Sanders, 2001).
Data on psychological variables and immunity in
cancer patients are accumulating. Correlational data
have shown relationships between heightened distress,
broadly defined [e.g., depressive symptoms (Sachs et al.,
1995), low social support (Lutgendorf et al., 2000;
Turner-Cobb et al., 2000)], and down regulated
immunity. Data from this trial (Andersen et al., 1998)
showed a robust relationship between patients' stress
and lower NK cell lysis and T-cell proliferative responses,
replicated in multiple assays, as patients entered the
trial. Longitudinal data showed that NK and T cells are
sensitive to different aspects of the stress response.
Specifically, T cell blastogenesis covaries with patients'
initial (peak) subjective stress, but NK cell lysis corre-
lates with change (reduction) in stress across time
(Thornton et al., 2007). Finally, the trial data showed
 Biobehavioral Intervention for Cancer Stress
that the intervention was associated with differential
improvements in T cell blastogenesis for the interven-
tion arm in comparison to declining levels for the
assessment arm (Andersen, Farrar et al., 2007; Andersen
et al., 2004).
Behavioral Pathways
There are important behavioral sequelae to stress (see
Figure 1). Negative health behaviors may increase in fre-
quency (Ng & Jeffery, 2003). Those anxious may use
alcohol or drugs to self-medicate (Bing et al., 2001;
Goeders, 2004; Johnstone, Garrity, & Straus, 1997).
Cigarette smoking and caffeine intake can increase during
periods of stress (Ng & Jeffery, 2003). Distressed indivi-
duals can have appetite disturbances and/or dietary
changes (Wardle et al., 2000). The taste of foods may
change with stress (Bergdahl & Bergdahl, 2002). Distur-
bances of taste or eating habits (e.g., food restriction or
taste aversions from chemotherapy) can occur (Ravasco
et al., 2004). Disturbed sleep can occur (Steptoe,
O'Donnell, Marmot, & Wardle, 2008).
The model suggests that health behaviors, in turn, may
affect immunity. In general, negative health behaviors
have an adverse, down-regulating effect on immunity,
and some appear to increase stress hormones (e.g.,
cortisol) as well. Alcohol usage appears to blunt immune
responses, e.g., impair natural killer (NK) cell and
interleukin-2 (IL-2) activity (Diaz et al., 2002; Frank,
Witte, Schrodl, & Schutt, 2004). Cigarette smoking is
associated with NK cell suppression and production of
pro- vs. anti-inflammatory cytokines (Zeidel et al., 2002).
The release of corticotrophin-releasing hormone (CRH),
a main component of the stress system, may suppress
appetite (Tsigos & Chrousos, 2002). Insomnia is asso-
ciated with nocturnal sympathetic arousal (i.e., increases
in circulating norepinephrine) and declines in NK cell
lysis (Savard et al., 2003). Difficulties may be com-
pounded with multiple negative health behaviors. For
example, depression and cigarette smoking are synergis-
tic, and yield lower levels of NK cell lysis than either one
alone (Jung & Irwin, 1999). In summary, studies indicate
several linkages between negative health behaviors and
elevations in stress-related hormones and/or lowered
immune responses.
Alternatively, if negative health behaviors can be
reduced and/or positive health behaviors increased,
important sympathetic and adrenocortical changes and/
or immunity changes may occur. Smoking abstinence,
even for a day, has been found to reduce cortisol levels
(Steptoe & Ussher, 2006) and increase NK cell cytotoxity
(Meliska et al., 1995). Nutritional improvements can
enhance immune responses and reduce rates of infection
(Galban et al., 2000). Physical activity (exercise) may have
255
positive consequences for immune (Fairey et al., 2005)
and endocrine systems (Mastorakos & Pavlatou, 2005; Na
et al., 2000).
The second behavioral factor is treatment compliance
(adherence). In general, depression is a risk factor for
noncompliance with medical treatment (DiMatteo, Lep-
per, & Croghan, 2000). In cancer, emotional distress
(McDonough et al., 1996) has been associated with low
rates of continuing (Ayers et al., 1994) and completing
chemotherapy (Levin, Mermelstein, & Rigberg, 1999).
The base rate of dropout is generally low (e.g., b5-10%),
except for maintenance therapies. Lengthy tamoxifen
treatment trials (e.g., 5 years duration) have had dis-
continuance rates among breast cancer patients ranging
from 23% to 40% (Fisher et al., 1998; Fisher et al., 1996;
Powles et al., 1998). Unfortunately, compliance has been
understudied in cancer, despite its importance.
Summary
The biobehavioral model is a useful heuristic for
understanding the interaction of psychological, beha-
vioral, and biologic factors relevant to the progression of
cancer. Data support the importance of the variables
identified in the model and their predicted relationships.
Indeed, the cancer stressor brings a negative, biobeha-
vioral cascade, but when the stressor is reduced via an
intervention, biobehavioral responses improve.
Overview of the Biobehavioral Intervention (BBI)
Format
The intervention was provided in groups (8 to 12
patients) led by two clinical psychologists. Therapists
followed a session-by-session manual and patients
received a companion treatment handbook. Sessions
were 1.5 hours, with an intensive phase of 18 weekly
sessions during the first 4 months and then a main-
tenance phase of 8 monthly sessions, for a total of 26
sessions (39 therapy hours) over 12 months. This
number of sessions was the same as that for some
survival trials (23 sessions; Kissane et al., 2007; Kissane
et al., 2004), half that of others (Goodwin, Leszcz, &
Ennis, 2001; Spiegel et al., 2007) and longer than one
(Boesen et al., 2007).
SIBCP significantly departed from other trials in the
spacing of sessions. We reasoned that the maintenance of
gains would be critical to achieve any survival effect. The
established efficacy of psychosocial interventions for
cancer patients comes primarily from analyses of post-
treatment outcomes. There are few data on the durability
of treatment effects and, to our knowledge, no discussions
of ways to maintain treatment gains. This circumstance is
not unique. Karoly and Anderson (2000) reviewed the
psychotherapy literature and found that less than 10% of
the papers addressed maintenance and/or relapse
256 Andersen et al.
prevention. Longer-lasting effects can be achieved by
simply offering more treatment, as has been shown in
psychotherapy studies (Hansen, Lamber, & Forman,
2002). This is also the case in cancer. Rehse and Pukrop's
(2003) meta-analysis discovered that the number of
sessions was the most important moderator of outcome,
more powerful than characteristics of the patients or
intervention methods used. Thus, we increased the
number of sessions beyond the typical 8 to 10, but more
importantly, extended the intervention period across
months. Our study of the mechanisms of the intervention
effectiveness found that, indeed, gains achieved during
the intensive phase were at least maintained, if not
increased, during maintenance (Andersen, Shelby, et al.,
2007). This was particularly true for reductions in
symptoms and signs of illness. Continued use of relaxation
training, communicating assertively to health care provi-
ders (oncologists), and exercising more were important
for continued improvements in health.
Procedures to Maximize Adherence
Treatment dropout was of particular concern as high
dropout or low attendance would threaten the validity of
the test of the survival hypothesis. We anticipated high
rates of fatigue and other symptomatology from ongoing
adjuvant cancer therapies. Also, some patients might
have fragile health from other chronic illnesses or aging
(20% of the sample was over 60). For reasons such as
these a procedure was devised to reduce the likelihood
of dropout, reduce attendance variability among patients
who remained, and achieve the prescribed treatment
dose for all. Secondarily, we also wanted to eliminate (or
at least minimize) disruption in the groups due to
absenteeism.
The first group session provided an orientation to the
intervention, and patients were asked to notify the
therapist in advance if they were to be absent. Patients
were also told that, with their permission, the group
members would be informed about the reason for their
absence to reduce worries/concerns about the missing
participant. Within 3 days of any absence, the lead
therapist conducted a telephone session with the absent
participant. The therapist discussed the week's topic,
assigned any homework, and provided an update on the
group members; handouts were mailed or faxed to the
participant. This effort was also facilitated by the patient
having a treatment handbook.
This was a successful procedure. Patients appreciated
the personal attention, expression of concern, and
opportunity to stay connected. When the participant
returned to the group, no “catch up” was necessary. There
were no differences between cohorts in attendance, there
was high intervention arm retention (93%), and patients
received an average of 92% of the intervention sessions.
Patients also reported very high satisfaction with the
telephone sessions.
Post hoc analyses suggest that therapy attendance
(treatment dose) was important for a further lowering of
risk of disease progression (Andersen et al., 2008). The
survival analyses were intent to treat and thus conducted
with all participants (N = 227). However, clinical trial
analysts may commonly exclude patients who received
little or none of the treatment being studied, with the
perspective that a more accurate view of the specific
efficacy of the treatment is then provided. Excluding 16 of
114 (14%) of the intervention arm patients who attended
less than 20% of the intervention sessions (i.e., 5 or fewer
of 26 sessions), the data were reanalyzed using an N of
211. Using the same analytic procedures, the results were
replicated. For comparison, however, the follow-up
analyses showed a 68% reduced risk of breast cancer
death for patients in the intervention arm when the low
attendance patients were removed, and a 56% risk
reduction when they were not (i.e., intent-to-treat
analyses).
BBI Components and Strategies: Intensive Phase
As specified by the model, the intervention was
designed to reduce stress, enhance quality of life
(operationalized as emotional adjustment, social adjust-
ment and support, and breast-specific concerns), increase
positive health behaviors, decrease negative health
behaviors, and improve compliance. With these as targets,
therapy components were designed anew or selected
from previously published, effective treatments for
anxiety reduction or symptom management. Table 1
summarizes the intervention targets, treatment compo-
nents and strategies, and their sequencing. See Andersen
et al. (2004) for the relevant outcomes for each
intervention component.
Following the first session, intensive sessions had a
similar, structured sequence of events. The group
environment was, by design, informal, welcoming, and
supportive. The group therapy room was simply furnished
with recliner chairs. The room was open 30 minutes prior
to the sessions so that patients could meet, greet one
another, and chat; coffee, juice, and snacks (e.g.,
crackers) were available. With the therapist's arrival the
reason (if known) for any member's absence was noted.
Relaxation training was done, providing a starting point
for individuals to unwind from the hurries of the day and
come together as a group. Afterwards, patients were asked
to open their notebooks to the day's topic and the lead
therapist (D.M.G-K.) usually began a content-laden
introduction. During and following this, group discussion
was prompted with the therapists' comments, redirec-
tions, or summaries as appropriate and any in-session
Table 1
BBI targets, components, and correspondence to session number, utilization assessment, and recommended utilization of the treatment component

Intervention Intervention Component Session Utilization Measure ⁎ Minimum Recommended Usage

Target Number
Stress ▪ Conceptual model: Relationship of stress and 1, 19 Using info. on stressors to As needed
immunity; Understanding stress and responses to it. modify behaviors
▪ Problem solving. 10-12, Problem solving As needed
20-21
Quality of Life:
Emotional ▪ Relaxation training. Also: Problem solving, positive 1-26 Relaxation training 1/day for 20 min. ea.

Biobehavioral Intervention for Cancer Stress

distress coping.
Social ▪ Social support: Identify social network, support 4-9, Identification and selection 1) Ask for emotional support 1/week.
adjustment needs, and contacts. 21, 22, 23 of support resources 2) Ask for task support 1/week.
▪ Assertive communication skills training. 5-7, 22 Assertive communication 3) Identify one new source of support
per month (emotional or task).
4) Communicate assertively 1/week with x
(specific person) about y (specific problem).
Compliance ▪ Assertive communication skills with 2-3, 5, Med. provider communication 1) Identify 1 question prior to next MD visit and
physician. Also: Disease/treatment information, 10-12, 20 get it answered.
planning appointments, goal setting. Relaxation training 2) Adhere to cancer treatment regimen.
Exercise 3) Keep all appointments (appear on specified
day/time).
Health Behaviors
Diet ▪ Strategies for low fat/high fiber food consumption. 14-16, 24 Eating less fat, eating more fiber 1) Reduce daily fat intake to a maintenance
Also: Food intake diary (2 × 3 days), energy balance level of 47 grams.
information. 2) Eat a maintenance level of 20-35 grams
of fiber per day.
Exercise ▪ Walking protocol and strategies to increase daily 13, 25 Use of strategies for increasing 3) Walk briskly (or equivalent) to 70-85% of
activity level. activity maximal heart rate, 3/week for 20 min. ea.
▪ Negative health behaviors. 14, 17 4) Increase x (specific behavior) by y (identify
method).
Physical ▪ Strategies for symptom management (e.g., nausea, 1-26 Relaxation training 1) Relaxation as recommended.
functioning fatigue, hot flashes, disturbed sleep) and increasing Medical provider communication 2) Increase activity level as recommended.
daily activity level. Exercise
⁎ See Andersen, Shelby, & Golden-Kreutz, 2007 for additional detail.

257
258 Andersen et al.
activities were accomplished. Sessions closed with assign-
ments (if any) and good-byes, with therapists and patients
often lingering to chat.
Stress Reduction and Enhancing Quality of Life (Emotional
Adjustment; Sessions 1-26)
There were three components. The first group meeting
provided to patients an explanation of Selye's General
Adaptation Syndrome (Selye, 1956), a conceptual model
for understanding their stress responses and adaptation to
cancer. Cancer stressors (e.g., diagnosis, surgery, selection
of adjuvant therapies) were discussed. We noted that
people did not have unlimited reserves for coping with
repeated stressful events: without resources, a state of
physical exhaustion would result. Thus, the goal was to offer
adaptive coping strategies that could be learned and
applied generically to stressors. Then, using a list we helped
each patient to identify her own warning signs of stress:
emotional (e.g., low mood, irritability), behavioral (e.g., low
energy/fatigue, memory difficulties), and body signs (e.g.,
pounding heart, abnormal breathing, headaches). Then,
the A (Activity/Event)—B (Beliefs/Automatic thoughts)—
C (Consequences/Feelings and Behaviors) model was
offered to explain common responses to cancer stressors.
Secondly, progressive muscle relaxation (PMR) train-
ing (Bernstein & Borkovec, 1973) was presented as a
primary strategy for coping with cancer stressors, lowering
tension on a daily basis, reducing the wear and tear on the
body from stress, and for reducing or controlling cancer
therapy symptoms (e.g., nausea, fatigue; Sessions 1-26).
Instruction began in the first session with a 45-minute, 16-
muscle-group procedure. Patients were provided with
cassette tapes for home use and urged to practice 3 at least
times per week, 20 minutes each. Thereafter, each session
began with PMR. Across sessions, PMR was modified as
proscribed (Bernstein & Borkovec, 1973) through to
Session 18. By then, patients could become deeply relaxed
when using a 2-minute, relaxation-by-recall procedure.
Third, problem-solving training (Sessions 10–12), fol-
lowing the principles of Goldfried and Davision (1976) and
Hawton and Kirk (1989), consisted of the following stages:
overview, defining and formulating target problems, gen-
erating solutions, making decisions, implementing solu-
tions, and verifying selected solutions. To learn the
principles, the group members worked collaboratively on
solutions for two common problems: fatigue and time
management. To enhance generalization, patients targeted
one or two other areas for problem-solving as homework.
Considering these three procedures, follow-up ana-
lyses (Andersen, Shelby, et al., 2007) indicated that more
frequent use of PMR was associated with the lowering of
emotional distress, more so than the other strategies. Also,
the combination of the conceptualization for under-
standing daily stressors and relaxation was associated with
improved health (i.e., reduction in symptoms, signs, and
cancer treatment toxicities).
Improving Quality of Life (Social Adjustment;
Sessions 4-7, 21, 22)
For some interventions, social support among group
members is a central element of treatment (Spiegel et al.,
1989). The SIBCP intervention was not conceptualized as a
“support group,” per se. However, we learned that as pa-
tients share their reactions to the cancer crisis, their pro-
blem solving and adaptive coping is fostered. For example,
the first SIBCP strategy aimed at improving social adjust-
ment was prompting patients to accept the spontaneous
offers of help from friends and family. The majority of
patients were extremely reluctant to do so, but they were
encouraged by other group members who had accepted
assistance and found it beneficial. There are other
examples that could be cited, but what is important to
note is that patients' feelings of involvement in the group
and receiving support from the group (i.e., cohesion) were
important for treatment outcome. Specifically, patients
reporting greater cohesion from the intensive, weekly
sessions also achieved greater improvement (e.g., lower
distress) and higher functional performance during the
maintenance phase (Andersen, Shelby, et al., 2007).
Three strategies for achieving improved social adjust-
ment were used. First, assertive communication skills,
modeled after the work of Jakubowski and Lange (1978),
assisted women in expressing their thoughts, feelings, and
needs to facilitate support from friends and family. The
same procedures were used to enhance patients' commu-
nication with health care providers and get their medical
needs met. Four techniques were taught: specificity and
clarity of one's message; direct communication; qowningq
one's message (e.g., use of qIq and qmyq in statements);
and asking for feedback. Skills were practiced across the
social relationship categories identified below.
Second, we helped patients identify their social
network: individuals with whom they had regular
contact, either in person, by telephone, or through
letters/email, as well as those with whom they felt
extremely close but did not have regular contact. We
encouraged patients to identify at least 10 individuals.
Next, patients used a simple diagram to identify how
close they felt to each person and then evaluated each
individual's capability for providing emotional support,
task support (e.g., helping with household tasks, child
care, etc.), both, or neither to the patient. Patients then
made a listing of their current needs for emotional or
task support and tried to “match” their needs to capable
members of their network. This exercise led patients
to (a) appreciate that they were not alone and (b) be
 Biobehavioral Intervention for Cancer Stress
realistic (and strategic) about who could (or could not)
meet their specific needs. We reasoned that with an
objective appraisal, patients would be more successful in
receiving the type and amount of support when it was
needed. Following the introduction of this strategy,
patients were to make one request of emotional support
and one request for task support per week.
Third, during consecutive sessions, three levels of
social relationships (i.e., coworkers, friends, and physi-
cians; family members and children of all ages; and
spouse/spouse equivalent) were examined. Therapists
provided didactic information regarding common psy-
chosocial reactions of these individuals to a person with
cancer. Patients discussed the joys and disappointments
in the responses of these individuals to their diagnosis,
identifying sources of satisfaction and areas of difficulty.
As described above, patients identified target individuals
for assertive communication and/or requests for
specific support.
Improving Quality of Life (Breast Specific; Sessions 8-9, 23)
This session followed that on social support from the
partner. The sequelae of breast cancer [e.g., body changes,
menopausal changes, symptoms with hormonal therapy
(e.g., vaginal discharge), hair loss with chemotherapy] and
impact on sexual self-schema (esteem) were discussed.
Information on normal sexual responding and the role of
hormonal responses in female sexuality was provided.
Coping with body and sexual changes as discussed in
Andersen and Elliot (1993) was also included. Educa-
tional materials were provided [e.g., American Cancer
Society (ACS) publication on sexuality and cancer] and
strategies for coping with loss of sexual desire, a common
problem, were emphasized, as was initiating communica-
tion with the partner about sexuality. If intercourse (or an
equivalent) activity was currently not possible, difficult, or
not desired (loss of desire is common during cancer
treatment), we emphasized maintaining emotional inti-
macy (or other forms of physical intimacy) with the
partner. Oftentimes couples refrain from holding, touch-
ing, etc., when intercourse is not occurring.
Compliance (Sessions 2-3, 5, 10-12, 20)
The few available data suggested that information
about the disease and treatment and enlistment of help of
significant others (i.e., social support; Richardson et al.,
1987) would be important strategies. Three were used.
First, disease and treatment information was offered (and
patients were urged to seek information as homework if
they wished) to reduce uncertainty, aid in medical
decision-making, and enhance compliance. Educational
materials were developed for incorporation into inter-
vention sessions and/or patients' independent use. Today,
259
similar materials are readily available from the National
Cancer Institute or the ACS. Secondly, patients were
encouraged to use relaxation and distraction to reduce
anxiety and cope prior to and during radiotherapy and/
or chemotherapy treatments and to control symptomatol-
ogy afterwards (Redd et al., 2001). These strategies were
also recommended to cope with anxieties with follow-up
oncology appointments. Third, assertive communication
(see description above) was recommended to enable
patients' direct communication with their health care
professions. Patients were also taught to prepare for
appointments (e.g., write down questions), use aids for
remembering physician recommendations (e.g., note
taking, tape recording), and reminded that they were
entitled to adequate time with their providers. Fourth, the
problem-solving component for managing fatigue (see
above) was very important as fatigue was moderate to
severe through the first 4 to 6 months of the intervention
for all patients as they received radiation and/or chemo-
therapy. While it improved thereafter, fatigue did not fully
resolve until 18 to 24 months (Thornton et al., 2008)
following diagnosis.
Health Behaviors (Sessions 13-17, 24, 25)
Increasing activity level. Exercise provides positive health
benefits (Courneya, 2003), mood improvements (Valenti
et al., 2008), and symptom reduction (Winningham,
2001). In Session 13, patients completed a questionnaire
(British Columbia Department of Health, 1975) to gauge
their readiness for exercise. Patients were taught how to
monitor their heart rate and determine an estimated
training heart rate range. They were then encouraged to
increase their daily activity level, aiming for at least 20
minutes of walking, three times per week, according to
the Winningham protocol (Winningham, 2001).
(Patients with pre-cancer exercise routines were encour-
aged to resume their preferred activity on the same
schedule.) Didactic information included how to set
realistic activity goals, schedule activity and rest cycles,
increase energy expenditure during activities of daily
living, and cope with exercise frequency setbacks.
Women unable to perform the walking protocol due to
treatment complications were provided with alternative
activity/rest goals.
Patients were also provided ACS information on
exercises for arm mobility, exercises were practiced in
session, and patients were urged to incorporate them into
their activity regimen. (Note: In conducting health
behavior change interventions, it is important that
physicians provide medical clearance for patients. Also,
medical consultation should be readily available for any
concerns regarding health behavior interventions or the
participation of patients in them.)
260 Andersen et al.
Diet. The dietary component was preceded by patients
completing two 24-hour food diaries (unannounced)
during Sessions 11 and 13. These were analyzed and sum-
marized by a dietician in Session 14. This provided
individualized information on fat and fiber intake to
each patient. It was used to illustrate the ease of avoiding
(e.g., processed meats, fast foods) or substituting foods
(e.g., skim for whole milk) to significantly reduce fat
intake. Also, the dietician emphasized the importance of
protein intake to increase energy and aid in recovery from
surgery and the adjuvant therapies. The intervention
target was to lower fat intake from the American norm of
60 grams/day to 40 and increase fiber, fruit, and vegetable
consumption to the ACS-recommended 5 to 9 servings per
day (Subar et al., 1992).
In conjunction with the dietary intervention, therapists
helped patients identify their emotional, behavioral, or
situational cues for eating (e.g., “I often find myself eating
when…”). From this' a patient distinguished if she needed
to change the cue (e.g., watch less TV), change the
behavior (e.g., eat healthy snacks rather than cookies), or
plan ahead (e.g., buy healthy snacks rather than chips) for
healthier choices. Effective procedures from weight
management programs (e.g., controlling portion size,
only eating at the kitchen table) were also reviewed and a
copy of the ACS Eating Healthy cookbook was provided.
Finally, during the course of the intervention we had
provided juice and inexpensive, low-fat snacks during the
sessions to introduce patients to alternatives to high-fat
snacking. In summary, the guiding conceptualization of
the dietary component was that of health behavior change
rather than dieting. (Note: Patients with significant weight
loss, a low albumin, or other indicators of compromised
nutritional status were monitored to ensure that the
dietary intervention was complimentary to any other
needed dietary care.)
Negative health behaviors. Only limited, focused efforts
could be used to help patients change negative or proble-
matic health behaviors (e.g., Manley et al., 1991).
Disturbed sleep patterns were addressed with information
on sleep hygiene (Savard et al., 1999), recommendations
for activity programming (exercise) during the day, and
relaxation was recommended for difficulty falling or
staying asleep. Regarding smoking, all patients were
queried as to their smoking status in Session 14. Usually
smokers will acknowledge a desire to reduce, if not stop,
smoking, and all were provided referral to cessation
experts in the community. Also, therapists framed
smoking cessation as an example of an important, health
behavior choice, emphasizing that the choice for cessa-
tion was the patient's, and that cessation would yield
immediate benefits toward a post-cancer, healthy lifestyle.
Group members provided ready support and encourage-
ment for reduction efforts. Patients' cessation efforts were
reassessed in Session 17 and monthly during mainte-
nance. Despite the few numbers of smokers enrolled in
the trial, significantly more patients in the intervention
arm reduced or stopped smoking (Andersen et al., 2004).
Preparation for Maintenance (Sessions 17, 18)
The Transtheoretical Model of Behavior Change
(Prochaska & DiClemente, 1983) provided a framework
and method. Not widely used in cancer control, this con-
ceptualization is more common to prevention research
(e.g., smoking cessation, fruit and vegetable consump-
tion, mammography screening; Greene et al., 1999;
Prochaska et al., 1994). It is suggested that people pass
through five stages of change: precontemplation (no
intention to change), contemplation (seriously consider-
ing change), preparation (taking steps to change), action
(actively involved in meaningful change), and mainte-
nance (maintaining meaningful change). As change
through the stages occurs, there is to be a change in the
decisional balance. Thus, the model integrates constructs
from Bandura's self-efficacy theory (Bandura, 1982) and
Janis and Mann's (1977) decisional balance model.
During Session 18, patients used a 5-item algorithm to
determine their stage of change for six target areas:
relaxation training, adherence to medical therapy, social
support, diet, exercise, and control of a negative/
problematic health behavior. For each target a minimum
criterion was specified (see Table 1). If a patient reported
no activity or did not intend to change in the next month
(the duration between maintenance sessions), she would
categorize herself as being in the precontemplation stage.
If there was intention to change, the contemplation stage
would be indicated. Patients in the action stage would have
reached the criterion (e.g., practicing relaxation three
times per week) within the past month. The criterion for
the maintenance stage was meeting the criterion behavior
for 6 months. The session ended with patients specifying
goals for each target area during the upcoming month.
BBI: Maintenance Phase
The same general format was used for Sessions 19–26.
A therapist led the group in relaxation. Patients reviewed
their goals for the previous month and rated their
attainment and change stage. Patients were generally in
the contemplation, action, or maintenance phases.
Therapists emphasized problem solving, social support
seeking, and increasing awareness of patients' personal
cues of distress. All of these strategies had been identified
previously (e.g., Urban et al., 1992) as central to
maintaining change. Therapists reviewed all of the
intervention strategies, covering a different topic each
session (see Table 1 for topics by session numbers). Each
session closed with goal-setting for the coming month.
 Biobehavioral Intervention for Cancer Stress
In addition, therapists prompted two extra-group
activities. Each patient was asked to set aside 1 hour per
week, scheduled at the same time as the group meeting
(e.g., 4:00 P.M. on Tuesdays) for her own “session.” We
encouraged patients to reflect on their progress and use
the time as a specific reminder to “take care of myself.”
Also, group members were prompted to maintain contact
with one another between sessions. All patients were
comfortable in sharing telephone or email contacts and
were paired as qphone buddiesq for biweekly contacts.
The latter two activities were included to facilitate
maintenance of the behavior change goals and to ease
transition to the end of the intervention.
Provisos
In comparison to other therapy literatures, intervention
research in cancer is still in development despite the
passage of almost 30 years (e.g., Gordon et al., 1980). Un-
like the cognitive behavior therapy research literature
which has compared components of a "package" (Borkovec
et al., 2002), RCTs with cancer patients have included
varied interventions with few replications (Goodwin et
al., 2001; Spiegel et al., 1989; Spiegel et al., 2007). The
biobehavioral intervention described here was designed
for a specific goal: to reduce risk of breast cancer recur-
rence and death. As such, it included some components
that other trials did not (i.e., health behaviors, compli-
ance) as previous investigators hypothesized that they
might account, in part, for survival findings (Fawzy et al.,
1993; Spiegel et al., 1989).
The health behavior component could be removed for
those not having the time or expertise to conduct these
specialized sessions. However, we should also note that
the patients enjoyed the dietary component as it
represented a change effort they could make on a daily
basis to improve their health. Our very brief exercise
instruction (i.e., one session plus monitoring) did not
achieve group differences in physical activity levels
(Andersen et al., 2004), but the process data suggest
exercise was relevant to outcomes. In the intervention
arm, there was a significant impact on compliance
(chemotherapy dose intensity) and health improvements
for those who exercised frequently compared to those
who did not (Andersen, Shelby, et al., 2007). The health
behavior sessions occurred consecutively, but the com-
pliance content was interspersed throughout the sessions.
We believe this component had something important to
offer. Clinically, patients appeared to be empowered by
the message that they should take charge of their medical
care and have the health care system work for them.
This intervention, like most in cancer, was offered in a
group format. We have since conducted it with individuals
and found it easy to do. In fact, individual treatment
might lead to greater gains, as has been shown when
261
individual and group treatment of mood and anxiety
disorders have been compared. Meta-analyses show effect
sizes for individual treatment to be substantially larger
than those for group treatment (Osborn, Demoncada, &
Feuerstein, 2006).
The Biobehavioral Intervention in Context
For those unfamiliar with interventions for cancer
patients, it might be informative to compare this inter-
vention with the most efficacious psychological treat-
ments currently available for anxiety and depressive
disorders: cognitive behavioral treatments (CBT). In
Table 2 we attempt to do so, with the reference point
being the BBI treatment. We specify content unique and
essential to each treatment and content essential but not
unique. As indicated, the unique components of each
treatment are very different. Essentially, BBI offers
detailed analysis and change in adherence, health
behaviors, and social relationships. BBI is conceptualized
to address the cancer crisis. In contrast, CBT is concep-
tualized to address the “crisis” (and chronicity) of
troublesome anxious or depressive emotions. It has
exhaustive coverage of cognitive change and systematic
monitoring and change of day-to-day activities and
troublesome emotions, thoughts, and behaviors. While
the BBI may change cognitions and/or increase activity
level, it does so only in the service of other goals (e.g.,
reducing cancer-specific stressors, increasing activity
through exercise) and, thus, not in a systematic manner.
While CBT may prompt patients to seek more informa-
tion about cancer or talk to one's physician, for example,
it does so in the service of goals, such as reducing worry or
increasing assertive skills.
The essential but nonunique elements are ones that are
specifically included in BBI and ones often used in CBT as
necessitated by a patient's unique difficulties. For exam-
ple, Beck and colleagues (Beck, Rush, Shaw, & Emery,
1979) discuss assertive training and role playing (e.g.,
Chapter 7—“Application of Behavioral Techniques”)
and alternative solutions (problem solving; e.g., Chap-
ter 8—“Cognitive Techniques”). It is also the case that
while relaxation is often a component of CBT treat-
ment of anxiety disorders, it is not a routine compo-
nent for CBT for depression.
What is “missing” from this intervention compared to
the typical CBT “package” for anxiety or depression? The
most obvious difference is the absence of focus on
changing cognitions. While some strategies did address
specific negative cognitions and behaviors (e.g., stress
cues, eating cues), we did not focus on cognitions, per se,
or use thought records. Like behavioral activation,
however, we made efforts to increase patients' engage-
ment in activities and contexts that might allow them to
experience pleasure, relaxation, or a sense of control,
262 Andersen et al.
Table 2
Comparison of the Biobehavioral Intervention (BBI) and Cognitive Behavioral Therapy (CBT) components
Biobehavioral Intervention (BBI)
Components UNIQUE and essential
1) Concept: Cancer stress is a psychological,
physiological, and behavioral phenomenon.
2) Adherence
a) Education re: Cancer disease/treatment
b) Coping with physical symptoms (e.g. nausea)
3) Health behavior change
a) Exercise and diet
b) Negative behaviors, e.g., smoking
4) Social adjustment change
a) Social network identification
b) Identify emotional and task support needs
c) Education re: Responses of others to cancer
5) Maintenance: Stages of change conceptualization
Components essential but NOT UNIQUE ⁎
1) Progressive muscle relaxation
2) Seeking information to cope
3) Assertive communication
4) Problem solving
⁎ Any of these strategies may be employed with CBT.
though it was not done or monitored systematically,
excepting that for PMR. Because stamina was limited,
patients were urged to make choices for enjoyable
activities with family/friends rather than the mundane
(e.g., dusting, vacuuming). Also, group treatment pro-
vided no venue for identifying or changing a patient's
core beliefs or schema about the self. However, we
emphasized that the cancer diagnosis and the months of
treatment that followed offered an opportunity to take
perspective on one's life and to choose which aspects of life
(or relationships) to be continued or reduced in fre-
quency or eliminated.
The intervention was designed to alleviate stress and
anxiety, though post hoc analyses show that it also
alleviated depressive symptoms (Thornton et al., in
press). This is not entirely surprising in view of the
comorbidity of anxiety and depressive symptomatology.
We found that patients entering the trial with significant
depressive symptomatology and receiving the interven-
tion improved across outcomes whereas depressed
patients in the assessment arm showed no improvements.
A stable distress trajectory for the assessment patients
suggests that significant depressive symptoms among
cancer patients may not remit without treatment. Thus,
the BBI might be worth considering in a second gene-
ration of trials focused on the cancer patient with major
depression, who is typically undiagnosed and untreated
(Dausch et al., 2004; Schwartz & Drotar, 2006).
Cognitive Behavior Therapy (CBT)
1) Information that describes emotions, their functions,
and how they become disordered.
2) Behavioral activation with monitoring
3) Cognitive change: Monitoring of negative avoidant
cognitions
4) Reducing negative affectivity (e.g., depression, anger,
anxiety, guilt) and emotional avoidance
5) Identifying and changing troublesome behaviors
(e.g., withdrawal, avoidance, dependency)
6) Challenging core beliefs about the self
7) Maintenance: Identifying obstacles to long
term change in depressive symptomatology
Summary and Conclusions
A biobehavioral model of cancer stress and disease
course provided the foundation for a clinical trial
testing the efficacy of an intervention including both
intensive and maintenance phases. Some have queried
and suggested to us that the diverse content and
multiple components of the BBI would be overwhelm-
ing for patients. We do not believe this to be the case
as, for example, patients provided high satisfaction
ratings for each of the components (Andersen, Shelby,
et al., 2007). Also, a guiding principle offered to the
patients was that “good things go together.” That is,
practicing relaxation, complying with treatment recom-
mendations, exercising, changing one's diet, etc., were
complimentary strategies to reduce stress, speed
recovery, and improve quality of life.
As clinical research progresses, focus needs to shift to
patients in greatest need. This is important, as cancer
patients with significant symptoms of depression and
anxiety are underserved. We would view BBI as best
suited to the 50% to 60% of patients responding to
cancer diagnosis and treatment with moderate to severe
distress. We have learned from this trial and our ongoing
studies that many, upwards of 50%, of the individuals
with moderate/severe distress had pre-cancer psycho-
pathology symptoms (e.g., major depressive disorder,
generalized anxiety disorder) such that the significant
 Biobehavioral Intervention for Cancer Stress
distress occurring with the cancer diagnosis represents
recurrent psychopathology. Our data suggest that this
type of distress does not resolve on its own. As noted
above, depressive symptoms for patients in the assess-
ment arm continued through the 12 months following
diagnosis, unlike those for patients who received the BBI
intervention.
To date, the majority of trials accrue patients and offer
psychological treatments in the earliest days of the cancer
crisis. A variety of data would attest that this strategy
should continue, as it not only alleviates initial stress, but,
having done so, reduces the likelihood of subsequent
distress, and meaning in life can be enhanced. Inter-
ventions should, however, be designed to optimize late
outcomes. Without planning and programming, main-
tenance does not occur. Achieving durable intervention
effects is, however, possible and an important step to
transition patients to stable functioning. We offer this
intervention as one strategy for doing so.
References
Andersen, B. L., & Elliot, M. (1993). Sexuality for women with cancer:
Assessment, theory and treatment. Journal of Sexuality and Disability,
11, 7–37.
Andersen, B. L., Farrar, W. B., Golden-Kreutz, D., Kutz, L. A.,
MacCallum, R., Courtney, M. E., et al. (1998). Stress and immune
responses after surgical treatment for regional breast cancer.
Journal of the National Cancer Institute, 90(1), 30–36.
Andersen, B. L., Farrar, W. B., Golden-Kreutz, D. M., Emery, C. F.,
Glaser, R., Crespin, T. R., et al. (2007). Distress reduction from a
psychological intervention contributes to improved health for
cancer patients. Brain, Behavior, and Immunity, 21(7), 953–961.
Andersen, B. L., Farrar, W. B., Golden-Kreutz, D. M., Glaser, R., Emery,
C. F., Crespin, T. R., et al. (2004). Psychological, behavioral, and
immune changes after a psychological intervention: A clinical
trial. Journal of Clinical Oncology, 22(17), 3570–3580.
Andersen, B. L., Kiecolt-Glaser, J. K., & Glaser, R. (1994). A
biobehavioral model of cancer stress and disease course. American
Psychologist, 49(5), 389–404.
Andersen, B. L., Shelby, R. A., & Golden-Kreutz, D. M. (2007). Results
from an RCT of a psychological intervention for patients with
cancer: I. Mechanisms of change. Journal of Consulting and Clinical
Psychology, 75, 927–938.
Andersen, B. L., Yang, H. -C., Farrar, W. B., Golden-Kreutz, D. M.,
Emery, C. F., Thornton, L. M., et al. (2008). Psychological
intervention improves survival for breast cancer patients: A
randomized clinical trial. Cancer, 113, 3450–3458.
Arndt, V., Merx, H., Stegmaier, C., Ziegler, H., & Brenner, H.
(2004). Quality of life in patients with colorectal cancer 1 year
after diagnosis compared with the general population: A
population-based study. Journal of Clinical Oncology, 22(23),
4829–4836.
Ayers, A., Hoon, P. W., Franzoni, J. B., Matheny, K. B., Cotanch, P. H., &
Takayanagi, S. (1994). Influence of mood and adjustment to
cancer on compliance with chemotherapy among breast cancer
patients. Journal of Psychosomatic Research, 38(5), 393–402.
Bandura, A. (1982). Self-efficacy mechanism in human agency.
American Psychologist, 37(2), 122–147.
Beck, A. T., Rush, A. J., Shaw, B. F., & Emery, G. (1979). Cognitive therapy
of depression. New York: Guilford Press.
Bergdahl, M., & Bergdahl, J. (2002). Perceived taste disturbance in
adults: Prevalence and association with oral and psychological
factors and medication. Clinical Oral Investigations, 6(3), 145–149.
263
Bergmann, M., & Sautner, T. (2002). Immunomodulatory effects of
vasoactive catecholamines. Weiner Klinische Wochenschrift, 114,
752–761.
Bernstein, D. A., & Borkovec, T. D. (1973). Progressive relaxation training:
A manual for the helping professions. Champaign, IL: Research Press.
Bing, E. G., Burnam, M. A., Longshore, D., Fleishman, J. A.,
Sherbourne, C. D., London, A. S., et al. (2001). Psychiatric
disorders and drug use among human immunodeficiency virus-
infected adults in the United States. Archives of General Psychiatry, 58
(8), 721–728.
Boesen, E. H., Boesen, S. H., Frederiksen, K., Ross, L., Dahlstrom, K.,
Schmidt, G., et al. (2007). Survival after a psychoeducational
intervention for patients with cutaneous malignant melanoma: A
replication study. Journal of Clinical Oncology, 25(36), 5698–5703.
Borkovec, T. D., Newman, M. G., Pincus, A. L., & Lytle, R. (2002).
A component analysis of cognitive-behavioral therapy for
generalized anxiety disorder and the role of interpersonal
problems. Journal of Consulting and Clinical Psychology, 70(2),
288–298.
Bower, J. E., Ganz, P. A., & Aziz, N. (2005). Altered cortisol response to
psychological stress in breast cancer survivors with persistent
fatigue. Psychosomatic Medicine, 67, 277–280.
Bradley, C. J., Neumark, D., Bednarek, H. L., & Schenk, M. (2005).
Short-term effects of breast cancer on labor market attachment:
Results from a longitudinal study. Journal of Health Economics, 24
(1), 137–160.
Courneya, K. S. (2003). Exercise in cancer survivors: An overview of
research. Medical Science Sports Exercise, 35, 1846–1852.
Dausch, B. M., Compas, B. E., Beckjord, E., Luecken, L., Anderson-
Hanley, C., Sherman, M., et al. (2004). Rates and correlates of
DSM-IV diagnoses in women newly diagnosed with breast cancer.
Journal of Clinical Psychology in Medical Settings, 11(3), 159–169.
Diaz, L. E., Montero, A., Gonzalez-Gross, M., Vallejo, A. I., Romeo, J., &
Marcos, A. (2002). Influence of alcohol consumption on
immunological status: a review. European Journal of Clinical
Nutrition, 56(Suppl 3), S50–53.
DiMatteo, M. R., Lepper, H. S., & Croghan, T. W. (2000).
Depression is a risk factor for noncompliance with medical
treatment: Meta-analysis of the effects of anxiety and depres-
sion on patient adherence. Archives of Internal Medicine, 160
(14), 2101–2107.
Engler, H., Dawils, L., Hoves, S., Kurth, S., Stevenson, J. R.,
Schauenstein, K., et al. (2004). Effects of social stress on blood
leukocyte distribution: The role of alpha- and beta-adrenergic
mechanisms. Journal of Neuroimmunology, 156(1-2), 153–162.
Fairey, A. S., Courneya, K. S., Field, C. J., Bell, G. J., Jones, L. W., &
Mackey, J. R. (2005). Randomized controlled trial of exercise and
blood immune function in postmenopausal breast cancer
survivors. Journal of Applied Physiology, 98, 1534–1540.
Fawzy, I., Fawzy, N. W., Hyun, C. S., Elashoff, R., Guthrie, D., Fahey,
J. L., et al. (1993). Effects of an early structured psychiatric
intervention, coping and affective state on recurrence and
survival 6 years later. Archives of General Psychiatry, 50, 681–689.
Fisher, B., Constantino, J. P., Wickerham, D. L., Redmond, C. K.,
Kavanah, M., Cronin, W. M., et al. (1998). Tamoxifen for
prevention of breast cancer: Report of the National Surgical
Adjuvant Breast and Bowel Project P-1 Study. Journal of the National
Cancer Institute, 90(18), 1371–1388.
Fisher, B., Dignam, J., Bryant, J. H., DeCillis, A., Wickerham, D. L.,
Wolmark, N., et al. (1996). Five versus more than five years of
tamoxifen therapy for breast cancer patients with negative lymph
nodes and estrogen receptor-positive tumors. Journal of the
National Cancer Institute, 88, 1529–1542.
Fountzilas, G., Skarlos, D., Dafni, U., Gogas, H., Briasoulis, E.,
Pectasides, D., et al. (2005). Postoperative dose-dense sequential
chemotherapy with epirubicin, followed by CMF with or without
paclitaxel, in patients with high-risk operable breast cancer: a
randomized phase III study conducted by the Hellenic Coopera-
tive Oncology Group. Annals Of Oncology, 16(11), 1762–1771.
Frank, J., Witte, K., Schrodl, W., & Schutt, C. (2004). Chronic
alcoholism causes deleterious conditioning of innate immunity.
Alcohol Alcohol, 39(5), 386–392.
264 Andersen et al.
Galban, C., Montejo, J. C., Mesejo, A., Marco, P., Celaya, S., Sanchez-
Segura, J. M., et al. (2000). An immune-enhancing enteral diet
reduces mortality rate and episodes of bacteremia in septic
intensive care unit patients. Critical Care Medicine, 28(3), 643–648.
Giese-Davis, J., Sephton, S. E., Abercrombie, H. C., Duran, R. E. F., &
Spiegel, D. (2004). Repression and high anxiety are associated
with aberrant diurnal cortisol rhythms in women with metastatic
breast cancer. Health Psychology, 23(6), 645–650.
Goeders, N. E. (2004). Stress, motivation, and drug addiction. Current
Directions in Psychological Science, 13(1), 33–35.
Golden-Kreutz, D. M., & Andersen, B. L. (2004). Depressive symptoms
after breast cancer surgery: Relationships with global, cancer-
related, and life event stress. Psycho-Oncology, 13(3), 211–220.
Golden-Kreutz, D. M., Thornton, L. M., Wells-Di Gregorio, S. M.,
Frierson, G. M., Jim, H. S., Carpenter, K. M., et al. (2005).
Traumatic stress, perceived global stress, and life events:
Prospectively predicting quality of life in breast cancer patients.
Health Psychology, 24(3), 288–296.
Goldfried, M. R., & Davison, G. C. (1976). Clinical behavior therapy. New
York: Holt Rinehart and Winston.
Goodwin, P. J., Leszcz, M., & Ennis, M. (2001). The effect of group
psychosocial support on survival in metastatic breast cancer.
New England Journal of Medicine, 345(24), 1719–1726.
Gordon, W. A., Freidenbergs, I., Diller, L., Hibbard, M., Wolf, C.,
Levine, L., et al. (1980). Efficacy of psychosocial intervention with
cancer patients. Journal of Consulting and Clinical Psychology, 48(6),
743–759.
Greene, G. W., Rossi, S. R., Velicer, W. F., Rossi, J. L., & Prochaska, J. O.
(1999). Dietary applications of the stages of change model. Journal
of the American Dietetic Association, 99(6), 673–678.
Hansen, N. B., Lamber, M. J., & Forman, E. V. (2002). The
psychotherapy dose-response effect and its implications for
treatment delivery services. Clinical Psychology: Science and Practice,
9, 329–343.
Hawton, K., & Kirk, J. (Eds.). (1989). Problem-solving New York: Oxford
University Press.
Hewitt, M., Breen, N., & Devesa, S. (1999). Cancer prevalence and
survivorship issues: Analyses of the 1992 National Health Interview
Survey. Journal of the National Cancer Institute, 91(17), 1480–1486.
Jakubowski, P., & Lange, A. J. (1978). The Assertive Option: Your Rights
and Responsibilities. Champaign, IL: Research Press.
Janis, I. L., & Mann, L. (1977). Decision making: A psychological analysis of
conflict, choice, and commitment. New York-London: The Free Press.
Jim, H. S., Richardson, S. A., Golden-Kreutz, D. M., & Andersen, B. L.
(2006). Strategies used in coping with a cancer diagnosis predict
meaning in life for survivors. Health Psychology, 25(6), 753–761.
Johnstone, B. M., Garrity, T. F., & Straus, R. (1997). The relationship
between alcohol and life stress. In T. W. Miller (Ed.), Clinical
Disorders and Stressful Life Events (pp. 247–279).
Jung, W., & Irwin, M. (1999). Reduction of natural killer cytotoxic
activity in major depression: Interaction between depression and
cigarette smoking. Psychosomatic Medicine, 61(3), 263–270.
Karoly, P., & Anderson, C. (2000). The long and short of psychological
change: Toward a goal-centered understanding of treatment
durability and adaptive success. In I. C. R. S. R. E. Ingram (Ed.),
Handbook of Psychological Changes (pp. 154–176). New York: John
Wiley and Sons, Inc.
Kissane, D. W., Grabsch, B., Clarke, D. M., Smith, G. C., Love, A. W.,
Bloch, S., et al. (2007). Supportive-expressive group therapy for
women with metastatic breast cancer: survival and psychosocial
outcome from a randomized controlled trial. Psycho-Oncology, 16
(4), 277.
Kissane, D. W., Love, A., Hatton, A., Bloch, S., Smith, G., Clarke, D. M.,
et al. (2004). Effect of cognitive-existential group therapy on
survival in early-stage breast cancer. Journal of Clinical Oncology, 22
(21), 4255–4260.
Kohm, A. P., & Sanders, V. M. (2001). Norepinephrine and beta 2-
adrenergic receptor stimulation regulate CD4+ T and B lympho-
cyte function in vitro and in vivo. Pharmacological Reviews, 53(4),
487–525.
Kornblith, A. B., & Ligibel, J. (2003). Psychosocial and sexual functioning
of survivors of breast cancer. Seminars In Oncology, 30(6), 799–813.
Levin, M., Mermelstein, H., & Rigberg, C. (1999). Factors associated with
acceptance or rejection of recommendation for chemotherapy in a
community cancer center. Cancer Nursing, 22(3), 246–250.
Lundstrom, S., & Furst, C. J. (2003). Symptoms in advanced cancer:
Relationship to endogenous cortisol levels. Palliative Medicine, 17
(6), 503–508.
Lutgendorf, S. K., Anderson, B., Sorosky, J. I., Buller, R. E., & Lubaroff,
D. M. (2000). Interleukin-6 and use of social support in
gynecologic cancer patients. International Journal of Behavioral
Medicine, 7(2), 127–142.
Manley, M., Epps, R. P., Husten, C., Glynn, T., & Shopland, D. (1991).
Clinical interventions in tobacco control. A National Cancer
Institute training program for physicians. Journal of the American
Medical Association, 266(22), 3172–3173.
Mastorakos, G., & Pavlatou, M. (2005). Exercise as a stress model and
the interplay between the hypothalamus-pituitary-adrenal and the
hypothalamus-pituitary-thyroid axes. Hormone and Metabolic
Research, 37(9), 577–584.
Mazzoccoli, G., Carughi, S., De Cata, A., La Viola, M., & Vendemiale, G.
(2005). Melatonin and cortisol serum levels in lung cancer patients
at different stages of disease. Medical Science Monitor, 11, 284–288.
McDonough, E. M., Boyd, J. H., Varvares, M. A., & Maves, M. D.
(1996). Relationship between psychological status and compli-
ance in a sample of patients treated for cancer of the head and
neck. Head and Neck, 18(3), 269–276.
Meliska, C. J., Stunkard, M. E., Gilbert, D. G., Jensen, R. A., &
Martinko, J. M. (1995). Immune function in cigarette smokers
who quit smoking for 31 days. The Journal of Allergy and Clinical
Immunology, 95(4), 901–910.
Na, Y. M., Kim, M. Y., Kim, Y. K., Ha, Y. R., & Yoon, D. S. (2000).
Exercise therapy effect on natural killer cell cytotoxic activity in
stomach cancer patients after curative surgery. Archives of Physical
Medicine and Rehabilitation, 81(6), 777–779.
Ng, D. M., & Jeffery, R. W. (2003). Relationships between perceived
stress and health behaviors in a sample of working adults. Health
Psychology, 22(6), 638–642.
Osborn, R. L., Demoncada, A. C., & Feuerstein, M. (2006).
Psychosocial interventions for depression, anxiety, and quality of
life in cancer survivors: Meta-analyses. International Journal of
Psychiatry in Medicine, 36(1), 13–34.
Powles, T., Eeles, R., Ashley, S., Easton, D., Chang, J., Dowsett, M., et al.
(1998). Interim analysis of the incidence of breast cancer in the
Royal Marsden Hospital tamoxifen randomised chemoprevention
trial. Lancet, 352(9122), 98–101.
Prochaska, J. O., & DiClemente, C. C. (1983). Self-change processes, self-
efficacy, and decisional balance across five stages of smoking cessation.
New York: Alan R. Liss, Inc.
Prochaska, J. O., Velicer, W. F., Rossi, J. S., Goldstein, M. G., Marcus,
B. H., Rakowski, W., et al. (1994). Stages of change and decisional
balance for 12 problem behaviors. Health Psychology, 13(1), 39–46.
Raison, C. L., & Miller, A. H. (2001). The neuroimmunology of stress
and depression. Seminars In Clinical Neuropsychiatry, 6(4), 277–294.
Ravasco, P., Monteiro-Grillo, I., Vidal, P. M., & Camilo, M. E. (2004).
Cancer: Disease and nutrition are key determinants of patients'
quality of life. Supportive Care in Cancer, 12(4), 246–252.
Redd, W. H., Montgomery, G. H., & DuHamel, K. N. (2001). Behavioral
intervention for cancer treatment side effects. Journal of the
National Cancer Institute, 93(11), 810–823.
Rehse, B., & Pukrop, R. (2003). Effects of psychosocial interventions on
quality of life in adult cancer patients: Meta analysis of 37
published controlled outcome studies. Patient Education and
Counseling, 50(2), 179–186.
Richardson, J. L., Marks, G., Johnson, C. A., Graham, J. W., Chan, K. K.,
Selser, J. N., et al. (1987). Path model of multidimensional
compliance with cancer therapy. Health Psychology, 6(3), 183–207.
Rontgen, P., Sablotzki, A., Simm, A., Silber, R. -E., & Czeslick, E. (2004).
Effect of catecholamines on intracellular cytokine synthesis in
human monocytes. European Cytokine Network, 15(1), 14–23.
Sachs, G., Rasoul-Rockenschaub, S., Aschauer, H., Spiess, K., Gober, I.,
Staffen, A., et al. (1995). Lytic effector cell activity and major
depressive disorder in patients with breast cancer: A prospective
study. Journal of Neuroimmunology, 59(1-2), 83–89.
 Biobehavioral Intervention for Cancer Stress
Savard, J., Laroche, L., Simard, S., Ivers, H., & Morin, C. M. (2003).
Chronic insomnia and immune functioning. Psychosomatic Medi-
cine, 65(2), 211–221.
Savard, J., Miller, S. M., Mills, M., O'Leary, A., Harding, H., Douglas,
S. D., et al. (1999). Association between subjective sleep quality
and depression on immunocompetence in low-income women
at risk for cervical cancer. Psychosomatic Medicine, 61(4), 496–507.
Schwartz, L., & Drotar, D. (2006). Posttraumatic stress and related impair-
ment in survivors of childhood cancer in early adulthood compared
to healthy peers. Journal of Pediatric Psychology, 31(4), 356–366.
Selye, H. (1956). The stress of life: A new theory of disease. New York:
McGraw-Hill.
Shelby, R. A., Golden-Kreutz, D. M., & Andersen, B. L. (2008). PTSD
diagnoses, subsyndromal symptoms, and comorbidities contribute
to impairments for breast cancer survivors. Journal of Traumatic
Stress, 21(2), 165–172.
Spiegel, D., Bloom, J. R., Kraemer, H. C., & Gottheil, E. (1989). Effect
of psychosocial treatment on survival of patients with metastatic
breast cancer. Lancet, 2(8668), 888–891.
Spiegel, D., Butler, L. D., Giese-Davis, J., Koopman, C., Miller, E.,
DiMiceli, S., et al. (2007). Effects of supportive-expressive group
therapy on survival of patients with metastatic breast cancer: A
randomized prospective trial. Cancer, 110(5), 1130–1138.
Steptoe, A., O'Donnell, K., Marmot, M., & Wardle, J. (2008). Positive
affect, psychological well-being, and good sleep. Journal of
Psychosomatic Research, 64, 409–415.
Steptoe, A., & Ussher, M. (2006). Smoking, cortisol and nicotine.
International Journal of Psychophysiology, 59(3), 228–235.
Subar, A. S., Heimendinger, J., Krebs-Smith, S. M., Patterson, B. H.,
Keller, R., & Pivonka, E. (1992). A day for better health: A baseline
study of americans' fruit and vegetable consumption. Rockville, MD:
National Cancer Institute.
Thornton, L. M., Andersen, B. L., Crespin, T. R., & CarsonIII, W. E.
(2007). Individual trajectories in stress covary with immunity
during recovery from cancer diagnosis and treatments. Brain,
Behavior, and Immunity, 21(2), 185–194.
Thornton, L. M., Andersen, B. L., Schuler, T. A., & Carson, W. E.,
(in press). A psychological intervention reduces inflammation by
alleviating depressive symptoms: Secondary analysis of a rando-
mized controlled trial. Psychosomatic Medicine.
Thornton, L. M., CarsonIII, W. E., Shapiro, C. L., Farrar, W. B., &
Andersen, B. L. (2008). Delayed emotional recovery after taxane-
based chemotherapy. Cancer, 113(3), 638–647.
265
Tsigos, C., & Chrousos, G. P. (2002). Hypothalamic-pituitary-adrenal
axis, neuroendocrine factors and stress. Journal of Psychosomatic
Research, 53(4), 865–871.
Turner-Cobb, J. M., Sephton, S. E., Koopman, C., Blake-Mortimer, J., &
Speigel, D. (2000). Social support and salivary cortisol in women
with metastatic breast cancer. Psychosomatic Medicine, 62(3),
337–345.
Urban, N., White, E., Anderson, G., Curry, S., & Kristal, A. (1992).
Correlates of maintenance of a low-fat diet among women in the
women's health trial. Preventive Medicine, 21, 279–291.
Valenti, M., Giampiero, P., Aielli, F., Verna, L., Cannita, K., Manno, R.,
et al. (2008). Physical exercise and quality of life in breast cancer
survivors. International Journal Medical Sciences, 5, 24–28.
Wardle, J., Steptoe, A., Oliver, G., & Lipsey, Z. (2000). Stress, dietary
restraint, and food intake. Journal of Psychosomatic Research, 48(2),
195–202.
Winningham, M. L. (2001). Strategies for managing cancer-related
fatigue syndrome A rehabilitation approach. Cancer Supplement, 92
(4), 988–997.
Yurek, D., Farrar, W., & Andersen, B. L. (2000). Breast cancer
surgery: Comparing surgical groups and determining individual
differences in postoperative sexuality and body change stress.
Journal of Consulting and Clinical Psychology, 68(4), 697–709.
Zeidel, A., Beilin, B., Yardeni, I., Mayburd, E., Smirnov, G., & Bessler, H.
(2002). Immune response in asymptomatic smokers. Acta
Anaesthesiologica Scandinavica, 46(8), 959–964.
Sources of support: National Institute of Mental Health (RO1MH51487),
National Cancer Institute (R01CA92704, K05 CA098133), with addi-
tional support from the American Cancer Society (PBR-89), the
Longaberger Company-American Cancer Society (PBR-89A), the U.
S. Army Medical Research Acquisition Activity (DAMD17-94-J-4165,
DAMD17-96-1-6294, and DAMD17-97-1-7062), and the Walther
Cancer Institute. We thank the patients for their participation and
guidance.
Address correspondence to Barbara L. Andersen, Ph.D., Depart-
ment of Psychology, 1835 Neil Ave., The Ohio State University,
Columbus, OH 43210-1222; e-mail: Andersen.1@osu.edu.
Received: August 21, 2008
Accepted: November 22, 2008
Available online 3 April 2009