Abstract
Background
Aromatase inhibitors (AI) have positive effects on disease-free life in
patients with Breast Cancer (BC); on the other hand, their side effects
especially arthralgia can be observed in many of patients. This study
aimed to evaluate the effectiveness of Progressive Relaxation Exercises
(PRE) on the common side effects of AI in patients with BC.
Methods
A total of 44 patients receiving AI were allocated to the study and
control groups in this randomized controlled, single-blind trial. The
study group (n=22) performed a combined (one-day supervised, and 3 days
home-based) PRE program 4 days/week, for six weeks. The control group
(n=22) was given advice about relaxation in daily life. Data was
collected initially and after 6 weeks of the intervention. Pain, quality
of life (QoL) and emotional status (ES) were assessed using the Brief
Pain Inventory (BPI), Functional Assessment of Chronic Illness Therapy
(FACT) and Hospital Anxiety and Depression (HAD) scales, respectively.
Results
Pain was significantly reduced within the study group
in Pain Severity (p=0.001) and
Pain Interference (p=0.01) sub-scores. Pain was also reduced between the
groups as compared using the Pain Severity (p=0.00) and Patient Pain
Experience (p=0.003) sub-scores; QoL and ES remained with no significant
difference either within the groups or between the groups
(p>0.05).
Conclusion
The results of this study showed that PRE significantly decreased pain
scores in BC patients receiving AI. Although the reduction in pain is a
valuable data even in the 6-week period in those cases, the long-term
effects of relaxation techniques need to be followed.
Keywords: Breast Cancer, Relaxation Therapy, Aromatase
Inhibitors
Introduction
Aromatase inhibitors (AI) are a class of medicines that work by blocking
the aromatase enzyme, which converts androgens into estrogen. Aromatase
inhibitors are used in the treatment of breast cancer to reduce levels
of circulating estrogen. Less estrogen means less stimulation for the
growth of estrogen receptor-positive (ER) breast cancer cells, resulting
in inhibition of BC progression. Approximately 80% of all breast
cancers are ER-positive.1,2
Although AI have positive effects on disease-free life, their side
effects especially joint pain and stiffness can limit their
use.3-5 In particular, arthralgia can be observed in
almost 50% of patients receiving AI6, Moreover,
patients on AI can experience side effects such as cognitive
dysfunctions7, anxiety and
depression8, sleep problems, and
fatigue9. All these adverse effects may seriously
deteriorate the quality of life (QoL) of patients.10Therefore, modulating QoL by decreasing side effects of AI has critical
importance in patients with BC.11
Anxiety and depression are the two main aspects of emotional status
(ES).12 ES is closely related to quality of life and
pain perception in patients with BC. While evaluating pain, the
emotional status should be assessed carefully.13,14Furthermore, emotional distress management is recommended as a routine
part of cancer care.15
Jacobson first described progressive muscle relaxation exercises (PRE)
in 1938.16 PRE is a widely used method with numerous
current modifications in different health
disorders.17,18 Physiological, perceptual, and
behavioral positive findings of muscle relaxation were
well-defined.19 Previous research had established that
recommendation of relaxation exercises may reduce the severity of
chemotherapy symptoms in patients receiving adjuvant chemotherapy for
BC.20 Physical activity such as aerobic exercise,
resistance exercises, Tai Chi and yoga, seems to reduce adverse effects
in patients receiving hormone therapy and improve
QoL.21,22
However, the effects of PRE in patients with BC receiving AI is not
well-known. This study aims to investigate the effects of PRE on
arthralgia, quality of life, and emotional status in patients with BC
receiving AI.
Materials and Methods
Study design
A two-armed, assessor-blinded, randomized controlled study was
conducted. BC survivors receiving AI were randomized to the study (PRE
performed) or control (no interventions) group. The medical records of
the patients were collected from the Breast Cancer Center of the local
hospital. Eligible patients were provided information about the study
and invited to participate in the study via phone calls. All the
assessments and exercise trainings were carried out in the
Physiotherapy Department of the
same hospital. Outcomes were assessed at the baseline and after 6 weeks
of intervention. The required information about musculoskeletal pain and
relaxation exercises were provided to all participants.
The sample size was calculated by using a previous study, which
mentioned the impact of yoga on functional outcomes in breast cancer
survivors with aromatase inhibitor–associated
arthralgias.23 The mean and standard deviation data of
the FACT-B parameter were used with a power (1-type II error) of 0.80
and a Type I error of 0.05. Therefore, it was aimed to recruit at least
20 participants per group. In total, with a dropout rate of 30%, it was
estimated that 26 patients would be recruited in each group.
Participants and randomization
Post-menopausal breast cancer patients who met the inclusion criteria
were identified based on a search across the medical records of Breast
Cancer Center between January 2014 and July 2018. Inclusion criteria
were as follows: having used AI for more than 6 months, diagnosis of
breast cancer stage 1-3, being a post-menopausal woman aged under 70
years, being hormone receptor-positive, and having received approval
from their physician for participating in the PRE program. The
participants were excluded from the study if they had communication,
neurological or orthopedic problems, participated in any physical
training in the previous six months, or had a diagnosis of lymphedema.
Among 120 patients with BC receiving AI, who were eligible as per the
study criteria, 54 participants agreed to participate in the study
voluntarily after phone call. (Fig 1) Participants were invited for the
baseline assessment at the hospital and the signed informed consent form
was obtained from each patient before assessment.
Participants were randomly allocated to the study group (n= 27) or
control group (n= 27) in 1:1 ratio by using a computer-generated list of
random sequence numbers. The randomization sequence was generated by a
physiotherapist using the hospital protocol number as the identifier for
each participant. Before randomization, a study researcher blinded to
allocation and experienced on oncologic rehabilitation examined patients
for musculoskeletal pain and other disorders and made patients fill out
the FACT, BPI and HAD forms. After a 6-week intervention, the same
assessor examined patients and made them fill out all the forms again.
Outcome measures
Pain
As primary outcome, The Brief Pain Inventory (BPI) assesses the
severity of pain and its impact on functioning. It has three dimensions
of pain assessments as follows: pain severity (BPI-PS), pain
interference (BPI-PI) and patient pain experience (BPI-PPE). The
validated questionnaire consists of 17 questions, which evaluate the
pain location, severity, and pain status, especially in the last 24
hours.24 The validity and reliability studies were
conducted for the brief pain inventory, which is frequently used in
cancer patients. Scores of 3-4 are defined as mild, 5-7 as moderate and
8-10 as severe pain in this scale.25
Quality of Life
As secondary outcome, The Functional Assessment of Chronic Illness
Therapy - Breast (FACT-B) instrument evaluates the all-round quality of
life in patients with breast cancer and is available in many languages.
The questionnaire includes five sub-scales that assess physical, social,
emotional, functional and another anxiety status. It has a 27-item
general (FACT-G) scale and a 10-item breast cancer-specific scale (FACT-
B) in which patients evaluate their status. Patients determine an
appropriate expression for themselves in the last seven days, with a
5-point scale as follows: 0: none; 1: very little; 2: slightly; 3:
quite; 4: too much. Higher scores indicate a higher quality of life. The
necessary permissions were obtained from the provider to access and use
the validated version.26
Emotional Status
As secondary outcome, The Hospital Anxiety and Depression (HAD)scale evaluates the emotional status for physically ill patients. It
consists of 14 questions 7 of which evaluate depression (HAD-D) and 7 of
which consider anxiety (HAD-A). The validity and reliability studies
were conducted for this Likert-type measurement. The cut-off score is
10/11 for the anxiety subscale and 7/8 for the depression subscale.
Accordingly, any points above these scores are considered to be at
risk.27
Intervention
The SPSS software (Copyright ©SPSS Version 26) was
used for statistical evaluation. The mean [95% confidence intervals
(CI)], standard deviations, and frequency rates were analyzed for
baseline characteristics. The group distributions were examined using
the Kolmogorov-Smirnov test. The group analysis was performed using the
non-parametric test methods due to the low number of participants. The
Mann-Whitney U test was used for the analysis of independent
quantitative data, and Wilcoxon test was used for the analysis of
dependent data. The McNemar test was used for dependent variables, and
the Chi-Square test was used for independent variables for studying the
qualitative data. Cohen’s Formula was used for calculating the effect
size of differences between and within the groups. The SPSS graphics
were used to create figures; and a P value <0.05 was
considered significant.