Trial Information

Mindfulness-Based Stress Reduction (MBSR) Symptom Cluster Trial for Breast Cancer Survivors

Breast cancer survivors are living longer and may be living with many symptoms incurred from
the disease and its treatment. Survivors from 1 to 2 years off treatment report continued
fatigue, depression, pain and sleep disturbances (Kenefick 2006; Byar et al. 2006). Patients
often present with several concurrent symptoms (Dodd et al. 2001; Esper and Heidrich 2005).
It is believed that symptoms tend to cluster together (two or more concurrent symptoms
related to one another and independent of other symptoms) and may have natural associations,
similar shared pathways and underlying mechanisms (Barsevick 2007). Currently, little is
known about how symptoms cluster in breast cancer survivors after treatment, underlying
mechanisms, and if interventions can influence multiple symptoms simultaneously (Lee et al.
2004; Cleeland et al. 2003). Very few studies have tested interventions during
post-treatment survivorship (Cimprich et al. 2005; Mishel et al. 2005; Stanton et al. 2005;
Scheier et al. 2005). Mindfulness-Based Stress Reduction (MBSR), a standardized form of
meditation and yoga, has been shown to be effective in reducing anxiety, depression and
stress in patients with chronic pain (Kabat-Zinn et al. 1992; Miller et al. 1995; Teasdale
et al. 2000; Kabat-Zinn et al. 1985). Preliminary results from 2 pilot studies conducted by
our research team provide support that MBSR for breast cancer survivors may be effective in
markedly reducing symptoms, increasing quality of life, and decreasing fears of recurrence
(Lengacher et al. 2009; Lengacher et al. 2006). This proposed study builds on our
preliminary data of the MBSR Breast Cancer Program (BC) to reduce stress, biological markers
of the stress response (pro-inflammatory cytokines) and improve physical, and psychological
symptoms and quality of life in breast cancer survivors.

We aim to determine: (i) the extent to which the MBSR(BC) program is efficacious in
improving outcomes; (ii) whether positive effects from MBSR(BC) are mediated through
increased mindfulness and reduced fear of recurrence; and (iii) if a subgroup of patients
can be determined to derive the most benefit from MBSR(BC). Formal specific aims are as
follows:

Aim (1). Evaluate the efficacy of the MBSR(BC) program in improving psychological and
physical symptoms, quality of life and measures of immune function and a stress hormone
(cortisol). We hypothesize that compared to the usual care regimen, patients randomly
assigned to the MBSR(BC) program will experience greater improvements at 6 weeks and
sustained improvements at 12 weeks in the following:

1. Individual psychological symptoms, including depression anxiety, and perceived stress;

2. Individual physical symptoms, including pain, fatigue and sleep dysfunction;

3. Quality of life;

4. Biological stress markers (pro-inflammatory immune cytokines, cellular adhesion
molecules, lymphocyte subsets) and a stress-related hormone (cortisol).

Aim (2). Test whether positive effects achieved from the MBSR(BC) program (defined in
1a-1d) are mediated through changes in mindfulness and fear of recurrence of breast cancer.
We hypothesize that:

1. Patients in the MBSR(BC) program will report greater increases in mindfulness and
larger reductions in fear of recurrence compared to patients assigned to the usual care
regimen.

2. Increased mindfulness will relate directly to improvements in psychological and
physical symptoms, quality of life and measures of immune function and a stress hormone
(cortisol).

3. Reductions in fear of recurrence will be associated with improvements in psychological
and physical symptoms, quality of life and measures of immune function and a stress
hormone (cortisol).

4. A primary pathway through which MBSR exerts its positive effects (defined in 1a-1d)
will be through increased mindfulness leading to reduced fear of recurrence of cancer.

Aim (3). Evaluate whether positive effects achieved from the MBSR(BC) program (defined in
1a-1d) are modified by specific patient characteristics measured at baseline. We
hypothesize that efficacy of the MBSR(BC) program will be greatest among patients with:

1. High anxiety, high perceived stress, low optimism and poor quality of life

2. Specific symptom profiles (i.e. highly distressed patients), as determined by grouping
(clustering) patients according to their presenting symptoms.

To achieve this research goal, we have proposed a 2-group randomized clinical trial among
300 breast cancer survivors who have undergone lumpectomy and/or mastectomy and radiation
and/or chemotherapy in the past two years. The MBSR(BC) program will be evaluated against a
waitlisted usual care regimen (UC), with patient assessments made at baseline, 6 weeks, and
12 weeks. Patient assessments will provide data on depression, state anxiety, perceived
stress, fatigue, pain, sleep, symptom severity, quality of life, mindfulness, fear of
recurrence, optimism and social support. Additionally, blood and saliva samples will be
collected from participants. Biological stress markers will be measured by blood specimen
collection; biological stress markers will include pro-inflammatory and anti-inflammatory
cytokines (IL-1β, TNF-α, IL-6, IL-10, IL-1-RA, TNF-RA, IL-8, IFN-gamma), cellular adhesion
markers (CD11a, CD54, CD62L, CD45RA, CD45RO) and lymphocyte subsets (CD3, CD19, CD16+56). A
stress hormone, cortisol, will be measured by saliva specimen collection. The MBSR(BC)
intervention is an adapted 6-week program that follows the curriculum of an 8-week program
established by Kabat Zinn and Santorelli. Prior to formal hypothesis testing, the
distributions of all explanatory and outcome variables, as well as covariates, will be
examined. For outcome variables with skewed distributions, appropriate transformations (e.g.
square root, logarithmic, etc.) will be performed to satisfy normality requirements for
parametric multivariable linear modeling. This will include choosing the transformation
which yields the lowest Anderson-Darling score. In instances in which appropriate
transformations cannot be achieved, non-parametric methods will be used.

Results from this study will advance conceptual and clinical knowledge of how a
stress-reducing intervention impacts symptoms among breast cancer survivors and in whom it
may be most efficacious. Determining stress-related biological effects may be applicable to
other stress-reducing intervention studies. This symptom and symptom cluster assessment and
intervention model will further our understanding of biology and behavior and test a
predictive and personalized model of health care.