Trial Information

A Prospective, Randomized Controlled Trial of Mindfulness-based Stress Reduction (MBSR) Among Women Operated for Breast Cancer

Original Research Protocol, Copenhagen January 2007 Cancer and Mindfulness: A prospective,
randomized trial of a psychosocial intervention among women operated for breast cancer

Background From the time of diagnosis cancer patients have a need for psychological support.
Many patients handle the situation by the help of friends and family, while others need
professional support to come to terms with different phases of life as a cancer patient.
Only few randomized trials have been conducted in order to determine what kinds of
professional support patients will benefit from. These studies conclude that the prevalence
of anxiety and depression in reduced. This is of major importance as depending of cancer
type, treatment modality, age and gender, a total of 10-50 % of Danish cancer patients
reports such well-defined psychosocial symptoms following the diagnosis of cancer.

Mindfulness meditation aims to increase the experience of presence and an increased relation
to several emotional and sensory experiences. Instead of being a technique aimed to control
and change unwanted psychological states the method is rather a way to stay present in the
here and now without judging and as such it has been developed into a stress reduction
method: mindfulness based stress reduction (MBSR). The method is taught within a group
setting by an instructor guiding the patients during a week long program. The method has
been evaluated within a variety of settings and has been found to effectively reduce
symptoms related to different stress and pain conditions i.e. psoriasis, chronic pain,
HIV/AIDS, anxiety and depression.2 Based on these experiences several programs have been
developed and the program developed by Williams and Kabatt-Zinn has gained status as the
most commonly applied and best validated. Within recent years the program has been included
into cognitive-behavioral therapy. But with potential effects not only as reduction of
symptoms but further opens the opportunity for participants to approach spiritual and
existential themes. The potential effect is therefore not limited to simple reduction of
symptoms but includes increased meaningfulness, quality of life and sense of coherence.

Nine studies of the effect of MBSR haw been conducted, including 10- 157 adult cancer
patients being taught MBSR in groups of mainly breast cancer patients, but only three of
these trials have been conducted as randomized controlled trials. I these trials patients
have self-referred (selection bias), analysis have not been adjusted for biological status
of the cancer disease (confounding), samples have been small (n=10-157) (type 2 error) and
patients have differed with regard to time since diagnosis (misclassification). Despite
these methodological limitations a tendency of positive effects of MBSR participation on
psychological and physiological outcomes has been observed.

Yet it is still not determined whether MBSR will provide cancer patients benefit improving
their daily life with cancer. Some important aspects have not been addressed in previous
studies: When MBSR is applied as an intervention dose-response relation has only been
observed among patients with a moderate level of symptoms. Thus sensitivity of MBSR in
relation to stages of cancer, levels of pain or negative effects of treatments. We still do
not know whether all cancer patients will profit from this type of intervention. Further the
influence of patient compliance and working alliance is still not explored.

The diagnosis of cancer accentuates existential dimensions as spirituality and quality of
life. Yet we do not know how MBSR can support patients in dealing with such themes. Be
review of literature regarding patients coping with cancer the patients demand for
interventions supporting their need to deal with existential themes is striking.

Aim We will conduct a randomized controlled trial among women diagnosed with primary breast
cancer in order to evaluate the effect of MBSR on depression, anxiety quality of life,
health behavior and psychological well-being.

Research questions

- We do not know whether all types of cancer patients will benefit from MBSR. Especially
patients compliance must be empirically documented

- Cancer accentuates an array of existential concerns and the effect of MBSR on these
subjective concerns must be examined

Inclusion All patient diagnosed with primary breast cancer in Department of Breast Surgery,
Copenhagen Hospital Herlev, will be invited to participate in the study and in the
randomization allocating patients to either MBSR intervention or treatment as usual control.
Patients diagnosed and in active treatment for major psychiatric disease, patients with
musculoskeletal disease and cardiovascular disease hindering MBSR participation, and
patients previously diagnosed with other cancers than non-melanoma skin cancer will be
excluded. A project nurse will contact eligible patients, deliver oral and written
information and collect informed consent. If the patient consents baseline questionnaire
will be administered.

Randomization will then take place. The project nurse will up-load patient data on secured
project home-page. Computer generated sequence will automatically assign a unique study
number to each patient indicating which study group she is allocated to. Result of the
randomization will be delivered to the patient by the project nurse and potential
disappointment will be handles at this point, and information regarding optional counseling
provided by the Danish Cancer Society will also be given.

Intervention group MBSR will be delivered in groups of maximum 20 participants. The course
will follow an 8 week schedule with 2-2½ hour sessions each week and instruction to practice
45 minutes daily at home. Upon conclusion of the course each group will participate in a
full-day course (8 hours). The courses will be delivered by a manual (including audio CDs)
developed by Antonia Sumbundu (see attached file). The group must meet in a quiet room large
enough to room 20 persons lying down, as well as mats, carpets and chairs. The courses will
be delivered in locations not affiliated with a hospital.

Control group The control group will receive treatment as usual and thus follow the standard
control program applied by the surgical department.

- Questionnaire Prior to randomization and as follow-up after 6 and 12 months both study
groups will be mailed questionnaires containing validated psychometric

- Hospital charts Descriptions of breast cancer operation, pathology of tumor as well as
day to day entries will be collected.

- Administrative registries Data regarding comorbidity of all eligible patients will be
collected in National Patient Registry and Central Psychiatric Registry upon
finalization of the project.

- Qualitative outcomes Data collected by standardized self-report instruments will be
supplemented by qualitative interviews inviting the intervention group participants to
present themselves by giving an account of the treatment and a personal evaluation of
the potential benefit.

Analysis

- Quantitative data Data will be stores in a database at the institute. Logistic
regression analysis will be applied to evaluate which background variables effects
participation. Analysis of outcomes will be conducted by applying multiple regressions
at each time point. For simultaneous analysis of all follow-up times a linear mixed
model with random effects of persons will be fitted. Outcomes as relapse and death
among intervention group in comparison to both control group and non-participants will
be analyzed by use of Cox regression model, controlling for the effect of biological
and demographic variables. Analysis will be conducted under supervision of a senior
statistician at the Department of Statistics and Epidemiology at the Institute.

- Qualitative data Based on the qualitative interviews a set of data-driven categories
will be developed. These categories will be quantitatively evaluated. The transcript of
the patient's self-presentation (approximately 2 pages) will be analyzed by use of
qualitative methods, allowing for grouping of content categories as expressed by the
patients. Statistical analysis will be applied to evaluate these categories.

Ethics Application of permission to conduct the study will be submitted to the The National
Committee on Health Research Ethics and to the Danish Data Protection Agency. In information
to patients regarding the study it will be stressed that participation is voluntary and that
patients withdraw without any explanation at any time, and that withdrawal will have no
influence on treatments delivered. Both written and oral consent must be given prior to
participation. A short report will be mailed to all participants upon conclusion of the
study. Vital status of participants will be checked in Central Persons Registry prior to any
sending of study questionnaire. Data kept in the study database will be encrypted ensuring
that only authorized scientific staff will be able to identify individuals. The encryption
code will be kept by study manager. Results will be reported as tables and figures hindering
identification of individuals. Also in the reporting of qualitative data will the quoted
participants be kept anonymous.

Reference List

1. Ross L, Boesen E, Dalton S, Johansen C. Mind and cancer: does psychological
intervention improve suvival and psychological well-being? European Journal of Cancer
2001.

2. Ott MJ, Norris RL, Bauer-Wu SM. Mindfulness meditation for oncology patients: a
discussion and critical review. Integr Cancer Ther 2006; 5(2):98-108.

3. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR. Fatigue in Breast
Cancer Survivors: Occurrence, Correlates, and Impact on Quality of Life. J Clin Oncol
2000; 18(4):743.

4. Bower JE, Ganz PA, Desmond KA et al. Fatigue in long-term breast carcinoma survivors: a
longitudinal investigation. Cancer 2006; 106(4):751-758.