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Vocal Music Therapy for Chronic Pain:
A Mixed Methods Feasibility Study

Ming Yuan Low, MA, MT-BC,1 Clarissa Lacson, MA, MT-BC,1 Fengqing Zhang, PhD,2

Amy Kesslick, MA, MT-BC, LPC,3 and Joke Bradt, PhD, MT-BC1

Abstract

Objective: The purpose of this study was to determine the feasibility and preliminary effects of a vocal music
therapy (VMT) program on chronic pain management.

Design: A mixed methods intervention design was used in which qualitative data were embedded within a
randomized controlled trial.

Setting: An urban nurse-management health center on the East Coast of the United States.
Subjects: Participants (N = 43) were predominantly Black (79%) and female (76.7%) with an average pain

duration of 10 years.
Intervention: Participants were randomly allocated to a 12-week VMT program or a waitlist control.
Outcome measures: We tracked consent rate (percentage of participants enrolled out of total number

screened), attrition rate, and treatment adherence. We used PROMIS
�

(Patient Reported Outcomes Measure-
ment Information System) tools to measure pain interference, pain-related self-efficacy, pain intensity, de-
pression, anxiety, positive effect, and well-being, ability to participate in social activities, and satisfaction with
social roles at baseline and week 12. VMT participants also completed the Patient Global Impression of Change
Scale. We conducted semistructured interviews to better understand participants’ experience of the intervention.

Results: The consent rate was 56%. The attrition rate was 23%. Large treatment effects (partial eta squared) were
obtained for self-efficacy (0.20), depression (0.26), and ability to participate in social activities (0.24). Medium effects
were found for pain intensity (0.10), anxiety (0.06), positive effect, and well-being (0.06), and small effects for pain
interference (0.03) and satisfaction with social roles (0.03). On average, participants felt moderately better after
completion of the VMT program (M = 4.93, standard deviation = 1.98). Qualitative findings suggest that VMT resulted
in better self-management of pain, enhanced psychological well-being, and stronger social and spiritual connections.

Conclusions: Recruitment into the 12-week program was challenging, but quantitative and qualitative
findings suggest significant benefits of VMT for chronic pain management.

Keywords: music therapy, pain management, clinical trials

Introduction

Chronic pain is a significant public health problemamounting to an annual health care expense of ap-
proximately half a trillion dollars in the United States

alone.
1

In 2016, the Centers for Disease Control and
Prevention issued recommendations to move away from
opioids and instead use nonpharmacological thera-
pies for the treatment of chronic pain.

2
The use of music

for the management of chronic pain is increasingly

Departments of 1Creative Arts Therapies and 2Psychology, Drexel University, Philadelphia, PA.
3Stephen and Sandra Sheller 11th Street Family Health Services, Drexel University, Philadelphia, PA.

ª Ming Yuan Low, et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms
of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which
permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the
source are cited.

THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

JACMVolume 26, Number 2, 2020, pp. 113–122Mary Ann Liebert, Inc.
DOI: 10.1089/acm.2019.0249

113

gaining interest, but more efficacy research is needed to
encourage health care providers to recommend its use to
patients.

3,4

To date, research on the use of music for pain has focused
primarily on listening to prerecorded music for acute pain
management with reported treatment benefits for reducing
pain intensity and opioid requirements.

5,6
A recent review

3

on the impact of music on chronic pain reported a moderate
effect size for pain (standardized mean difference = 0.60),
but results were inconsistent across studies (I

2 = 60%). The
majority of the studies (11/14) in this review employed
listening to prerecorded music; one study used choir singing,
and two studies used listening to live music.

The pain-reducing effects of music are often attributed to
music’s ability to distract and relax. However, chronic pain
is a complex phenomenon that affects individuals physi-
cally, mentally, socially, and spiritually and its management,
therefore, requires interventions that go beyond cognitive
distraction.

7
Therefore, we developed a vocal music therapy

(VMT) treatment program that addresses biopsychosocial
components of chronic pain management.

8

Music therapy is the clinical use of music interventions to
help clients optimize their health within a therapeutic rela-
tionship with a board-certified music therapist.

9,10
The VMT

group sessions use toning (i.e., singing of elongated vowels)
and humming, music-guided breathing, group singing, vocal
improvisations, verbal processing of emotions and thoughts
evoked by the music experiences, as well as psychoeduca-
tion about how music can address biopsychosocial factors
that impact chronic pain management. We briefly summa-
rize here the intervention’s theoretical framework, but
readers are referred to Bradt et al.

8
for a more in-depth

discussion.
On a bioneurological level, music listening and music

making activate brain areas involved with reward, emo-
tion, and arousal such as the nucleus accumbens, amygdala,
anterior insula, cingulate cortex, orbitofrontal cortex, and
mediodorsal thalamus, through which affective and cogni-
tive modulation of pain can be achieved.

11–13
On a psycho-

logical level, toning and humming are used to help enhance
body awareness, promote a positive connection with one’s
body, and facilitate relaxation. Since people with chronic
pain often try to disconnect from their body to ‘‘escape’’
the pain, these are considered important mechanisms in
chronic pain management.

14

Singing and active music making also help facilitate
emotional expression; emotional expressivity has been
shown to improve a sense of well-being and self-reliance in
people with chronic pain.

15
Finally, group music making

facilitates social inclusion and a sense of belonging.
16,17

Because people with chronic pain often feel isolated, this is
an important aspect of the VMT group.

The VMT program was initially tested as an 8-week
program.

8
Study findings were promising with large and

moderate effect sizes for pain-related self-efficacy and
pain interference, respectively, but participants unanimously
agreed that a longer program was desirable. Yet, concerns
were raised by health care providers at the study site about
the feasibility to recruit people with chronic pain to a
lengthier program. Therefore, the purpose of this mixed
methods feasibility study was to (1) determine the feasibility
of a 12-week VMT protocol; (2) provide estimates of effect

for core outcomes in chronic pain management; and (3)
obtain qualitative data about participant experiences of the
VMT program.

Materials and Methods

Study design

We employed a mixed methods intervention design,
18

in
which qualitative data (i.e., semistructured interviews) were
embedded within a randomized controlled trial. Participants
were randomized to the VMT or waitlist control (WLC)
treatment arm using a computer-generated list of random
numbers. Allocation concealment was achieved through the
use of sequentially numbered, opaque, sealed envelopes.
Since self-report measures were used for all outcomes, out-
come assessment could not be blinded as participants were
aware of their treatment allocation. However, the statistician
was blinded to group assignments (Fig. 1).

Participants

Participants were recruited from an urban nurse-managed
health center that predominantly serves inner-city, low-
income African Americans. Eligibility criteria are included
in Table 1. Participant demographic and clinical character-
istics at baseline are presented in Table 2. The majority of
the participants were female (76.7%), were black (79%),
were on disability leave (60.5%), and had an average pain
duration of 10 years. No significant between-group differ-
ences were present at baseline. The study was approved by
an Institutional Review Board. Informed consent was ob-
tained from all participants. We recruited participants in
three waves. In each wave, participants were randomly as-
signed to VMT or WLC. WLC participants were invited to
participate in the VMT intervention after completion of the
outcome measures at the end of the waitlist period.

Interventions

Vocal music therapy. Participants in the VMT treatment
program received twelve 90-min weekly group therapy
sessions (four to six participants). Sessions were led by a
board-certified music therapist. The VMT sessions followed
a similar structure, but were each focused on a different
topic related to music-based pain management (Table 3).

After a brief music-guided deep breathing exercise and
verbal check-in, the music therapist led the participants into
toning (i.e., singing elongated vowels) and humming expe-
riences. Using the voice in this manner can help facilitate
greater body awareness and promote relaxation. The group
then talked about somatic sensations experienced during the
breathing and toning exercises.

The session then moved into vocal music improvisations.
Percussion instruments were often added, resulting in en-
ergetic music making. These improvisations provided op-
portunities for emotional expression. Furthermore, group
music making enabled participants to relate to others and
share some of their struggles in novel ways. Verbal pro-
cessing after the improvisation often evolved into additional
improvisations focused on the main ideas of the group
discussion.

Throughout the sessions, psychoeducation was pro-
vided about how music can address biological (e.g., music

114 LOW ET AL.

stimulates dopaminergic activity resulting in improved
mood), psychological (e.g., song lyrics can help validate
one’s feelings), and social (e.g., group music making creates
a sense of belonging) factors that play an important role in
chronic pain management. Education about why and how
music can address pain management can help with trans-
ferability of skills and knowledge outside of the session
room and equips participants to explain to family and
friends how music-based self-management techniques help
them with their pain.

Each session ended with singing a song listed by one of
the group members during intake. Participants were asked to
underline a lyric that was particularly meaningful to them
and could possibly be a source of emotional support during
the week. The therapist then facilitated a discussion about
the meaning of the selected lyrics.

8
The music therapist was

trained by J.B. using a treatment manual. Each session was
recorded and reviewed by J.B. to ensure treatment fidelity.

The original protocol tested in a previous study consisted
of eight 60-min sessions. The 12-week protocol was very
similar to the 8-week protocol, except that (1) the longer

session length allowed for more time for each music expe-
rience and group processing and (2) the longer program
length allowed for review sessions to revisit insights and
music-based pain management skills gained. The VMT
treatment manual will be published in the near future.

Waitlist control. Participants in the WLC group received
care as usual at the health center. At the center, chronic pain
management typically consists of pharmacological treat-
ment and physical therapy services. Additional comple-
mentary services are available, including yoga and fitness
classes.

Outcome measures

To determine feasibility, we tracked the following: (1)
consent rate (percentage of participants enrolled out of total
number screened); (2) attrition rate; and (3) treatment com-
pliance (number of sessions attended). To measure the ef-
fects of the intervention, we used the Patient Reported
Outcomes Measurement Information System (PROMIS

�
)
19

short forms (SF) to measure pain interference (SF-6b),
pain-related self-efficacy (SF-6), pain intensity (SF-3a),
depression (SF-4a), anxiety (SF-4a), positive effect, and
well-being (SF), ability to participate in social activities (SF-
4a), and satisfaction with social roles and activities (SF-4a).
Finally, participants rated their perception of improvement
using the Patient Global Impression of Change Scale (PGIC).

20

Measurements were administered at baseline and week 12.
After completion of the week 12 measurements, participants
(including WLC participants who opted to receive VMT after
the WLC period) were invited to participate in a semi-
structured interview aimed at better understanding their ex-
perience of the intervention (Appendix 1). Measurements and
interviews were administered by research assistants.

FIG. 1. Participant flow chart.

Table 1. Study Eligibility Criteria

Inclusion criteria Exclusion criteria

English-speaking
adults

Moderate to profound auditory
deficits

Age 18 or older Severe progressive medical or
neurological comorbidities

Chronic pain
for ‡3 months

Severe psychiatric disorder

Pain impact score
of ‡27 (moderate
impact)

a

Cognitive impairment
Current alcohol or drug problem
Currently receiving music therapy

services

a
Impact score items derived from Deyo et al.

35

VOCAL MUSIC THERAPY FOR CHRONIC PAIN 115

Data analysis

Quantitative data. For each of the outcome variables, we
compared the average difference between the VMT and WLC
conditions in improvements of the outcome from baseline to
week 12. T-scores were used for all PROMIS tools.

21
Raw

scores were used for the PGIC. Due to the small sample size,
mean difference of improvement from baseline to week 12
between the two conditions and the 95% confidence interval
(CI) was reported and used for inference. In addition, we
compared the improvement in the outcomes between the two
conditions controlling for baseline values. Partial eta squared
from ANCOVA was used to quantify the effect size and

was interpreted as small (0.01), moderate (0.06), and large
(0.14).

22,23
Given the limited sample size, we based our in-

ference on effect sizes.
24,25

Qualitative data. The transcripts of the interviews were
imported into MAXQDA 11

26
and analyzed by two coders

( M.Y.L. and C.L.) to ensure scientific rigor. We used the-
oretical thematic analysis procedures as outlined by Braun
and Clarke.

27
Coding was based on a semantic approach in

which codes are derived from ‘‘the explicit meaning of the
data and the analyst is not looking for anything beyond what
a participant has said’’

27
(p. 84). After codes were agreed

upon by both coders, they were organized into categories.
These were presented to J.B. for input and were compared
against the text excerpts associated with the codes for ver-
ification. The categories were then organized into broader
themes. After final categories and themes were agreed upon,
definitions for the categories and themes were developed.

Results

Feasibility

The consent rate was 56%. Of the 43 participants who
completed the baseline, 33 completed the postintervention
measures. This represents an attrition rate of 23% (Fig. 1).
Of the VMT participants, nine participants attended nine or
more sessions. Failure to attend a session was mainly due to
childcare issues, family emergencies, bad weather, health
issues, and traveling.

Preliminary efficacy

Table 3 details the mean change scores (baseline to week
12) and standard deviations (SDs) for each group as well as

Table 2. Sociodemographic and Clinical Characteristics of Study Participants at Baseline

Characteristic Music therapy (n = 22) Waitlist control (n = 21) p

Age, years, mean (SD) 48.76 (9.95) 51.38 (16.87) 0.12
Gender, female, n (%) 16 (72.73) 17 (80.95) 0.45
Race, n (%) 0.20

Black 18 (81.82) 16 (76.19)
Caucasian 3 (13.64) 0 (0)
Asian 1 (4.5) 0 (0)
American Indian or Alaska Native 0 (0) 1 (4.8)
Multiracial 0 (0) 4 (19.05)

Employment, n (%) 1.0
Employed 3 (13.63) 2 (9.52)
Unemployed 4 (18.18) 3 (14.29)
Retired 1 (4.5) 2 (9.52)
On disability 13 (59.1) 13 (61.9)

Duration of pain, years, mean (SD) 9.43 (7.02) 10.43 (11.13) 0.68
Pain diagnosis,

a
n (%) 0.71

Arthritis 8 (36.36) 10 (47.62)
Degenerative disc/spinal stenosis 2 (9.09) 3 (14.29)
Neuropathy 3 (13.63) 1 (4.76)
Fibromyalgia 2 (9.09) 2 (9.52)

Pain impact score 37.40 (6.64) 39.19 (6.39) 0.36
Prior music performance experience,

b
n (%) 0.75

Yes 13 (59.1) 11 (52.38)
No 8 (38.10) 10 (47.62)

a
Most commonly reported pain diagnoses.

b
Having played an instrument or sung in a choir.

SD, standard deviation.

Table 3. Session Topics

Session
number Session topic

1 Introduction and rapport building
2 Music making to enhance body awareness
3 Music-based techniques to promote self-care

and acceptance
4 Music-based self-management of pain and stress
5 Music as motivator for physical activity
6 Review session: Review skills learned/insights

gained to date
7 Music as a source of strength and inspiration
8 Emotional expressivity through music
9 Enhancing social support through music

10 Music as source of empowerment
11 Develop plan for maintenance of music-based

skills
12 Closure session

116 LOW ET AL.

the effect sizes. There was a large treatment effect of VMT
for pain-related self-efficacy, depression, and ability to par-
ticipate in social activities. The 95% CIs associated with
these large effect sizes suggest that these findings were sta-
tistically significant. Medium treatment effects were found
for pain intensity, anxiety, and positive affect and well-
being, and small effect sizes for pain interference and sat-
isfaction with social roles. The 95% CIs of these medium
and small effect sizes suggest that these were not statisti-
cally significant. On average, PGIC scores (M = 4.93, SD =
1.98) suggest that participants felt moderately better after
completion of the VMT program (Table 4).

Qualitative results

A total of 25 participants took part in the semistructured
interviews. All participants reported that the VMT sessions
were beneficial in helping them manage their pain inside
and outside of sessions (Theme 1, Pain Management). One
participant remarked, ‘‘Every time I play the instruments, it
helped me with my pain [.] That drum playing changed
my pain in some kinda way. ‘Cuz I didn’t have it [pain] once
I stopped doing the drums.’’ Participants shared that they
used VMT strategies to assist them with their daily activities
and chores or for motivation in the morning: ‘‘I wasn’t
feeling too good this morning. I turned on some music and it
took my mind off of that feeling. I was able to get dressed on
time and I made it here on time.’’

Some participants reported using music-based skills as al-
ternatives to their pain medication as the music helped to soothe
the pain and refocus their attention. Other participants stated
that the music made their pain ‘‘go away’’: ‘‘That day I was
having a lot of pain. We started singing and [.] it just went
away.’’ One person commented how purposefully music lis-
tening helped them with daily activities: ‘‘There are certain
songs I like, I can get into the rhythm of them. I just focus on the
music part, and it gave me a rhythm. As long as I was listening
to the music when I was working, I was able to keep going.’’

Many participants reported enhanced psychological well-
being in response to the VMT experiences and the psy-
choeducation about how music can address different factors
that influence their pain (Theme 2, Improved Psychological
Well-being). Participants shared that the VMT program led

to (1) better understanding of the contribution of stress and
other emotions to their pain, (2) greater awareness of the
presence of stress and uncomfortable emotions, and (3)
learning new music-based skills to help deal with mental
states that exacerbated their pain. One participant shared the
following: ‘‘I have step-children that I take care of. It can
become overwhelming. [Music] helps me just take that
moment to woosh (sic) and [.] release that negativity so
they don’t see that and feel that.’’

Some participants told us that they are now more inten-
tional with their use of music and that they create playlists
for specific purposes. Participants also emphasized that
learning to be kinder to oneself, achieving mindfulness, and
understanding who they are were important skills gained from
the program. One person shared that ‘‘keeps you away from
that self-blame—because that [self-blame] adds to the pain.’’
A large number of comments referred to feeling empowered to
prioritize one’s mental health and physical needs over de-
mands by others and seeking out things in life that bring joy.
Participants also appreciated that attending the program was a
form of self-care as expressed by one participant: ‘‘It made me
feel like I’m doing something for myself.’’

The third and final theme (Developing Meaningful Con-
nections) relates to music aiding in facilitating deeper
connections with one’s spirituality and stronger bonds with
others. One participant commented, ‘‘The spiritual aspect of
music and the emotional feelings that I got from just beating on
the drum, or playing the tambourine, or that ocean drum!’’

Many participants reminisced fondly about the bonds
among the group members that were created through the
VMT program. One participant said, ‘‘It was wonderful
because the group started out with everybody was in their
little shell. [.] And on the recording [excerpts from ses-
sions] that we heard after the group, we just heard our story,
and like how amazing how everybody developed. And we
became united. We became a family.’’ Another participant
appreciated the accepting and nonjudgmental environment
the group provided, ‘‘With friends or family or romantic
partners or even doctors, sometimes struggling so much to
explain intermittent, invisible chronic pain to the point of
disability [.] Hearing and being understood and sharing
just felt really comfortable and in a way that I had not ex-
perienced.’’ Participants shared that these bonds continued
outside of the sessions (Table 5).

Table 4. Change in T-Scores, Mean Difference and Effect Size

Outcome

Change score (SD)
a

MD (95% CI)
b

Effect size (Zp
2
)VMT WLC

Pain-related self-efficacy 4.84 (5.14) -0.26 (4.76) 5.10 (1.52 to 8.68) 0.20
Pain interference -2.46 (5.06) -0.45 (3.52) -2.01 (-5.17 to 1.15) 0.03
Pain intensity -5.7 (7.24) -1.86 (4.47) -3.85 (-8.19 to 0.49) 0.10
Anxiety -2.42 (8.55) 0.39 (7.32) -2.82 (-8.56 to 2.94) 0.06
Depression -4.92 (4.83) 2.56 (7.99) -7.48 (-12.25 to -2.71) 0.26
Positive affect and well-being 0.14 (6.8) -2.22 (5.96) 2.36 (-2.27 to 6.98) 0.06
Ability to participate in social activities 2.26 (3.62) -2.55 (6.53) 4.81 (0.99 to 8.62) 0.24
Satisfaction with social roles 1.59 (5.82) -0.51 (6.86) 2.10 (-2.49 to 6.70) 0.03

a
change from baseline to week 12.

b
Ninety-five percent CI intervals that do not include the value zero suggest that the findings are statistically significant.
Zp

2
, partial eta squared based on ANCOVA.

CI, confidence interval; MD, mean difference; SD, standard deviation; VMT, vocal music therapy; WLC, waitlist control.

VOCAL MUSIC THERAPY FOR CHRONIC PAIN 117

Table 5. Qualitative Findings

Themes and definitions Categories and definitions Example quotes

Theme 1 Pain
management:
The VMT program
offers participants
strategies to manage
pain in their daily lives.

Enhanced physical
functioning:
Music engagement helps
to improve activity
levels and ability to do
chores

But I use the soft jazz just to help with. I just sit there and
listen to it and I close my eyes. And I just rub my knees
[.] and when I feel like the feeling is going to be okay
and I can get up and not have a limp or anything, I get
up. And then, I don’t have no limp. The knee don’t be
bothering me.

I use to could not even walk 2 or 3 blocks. I would have to
like really sit down and take a breather. But it just seemed
like once I came here [.] and we just got into the
mood.once everything was over, I’d go home and I’m
like ‘‘I’m not in no pain at all.’’ And I never realize it and
I’m like doing all this stuff (chores) in the house.

Reducing pain:
Music brings pain relief
through its soothing
qualities as well as
through refocusing of
attention

I would describe it [the music] as a de-stressor. A way to
rethink, recharge your mind in a different direction and
also to take your mind off the pain.I’m not going to say
it can totally go away but it’ll subside a little to a point
where you’re functional.

I liked the ocean drum. That is really soothing, and it just
relaxed my whole body. I just listened to the sound of it, and
it takes you to sitting on the beach (in your imagination) and
just watching the waves. It was really peaceful.

When the pain begins to come, I try to hum [.] just direct
my attention to something else.

Theme 2 Improved
psychological well-
being:
VMT strategies help
manage difficult
psychological and
emotional states that
contribute to pain.

Achieving mindfulness:
Music helps participants
be more present by
creating a relaxed and
clearer state of mind.

A lot of the music that we’ve used were meditative, so it
kind of allows me to broaden like, my mind and my
perception.with sounds.

I do music for de-stress. And to take my mind off the
pain.it’s like a rethinking process. mindfulness. So
when I’m mindful, first I do mindful exercises and
breathing. Recognizing my own breath. My own
heartbeat. And it tends to calm down.

Empowerment:
VMT empowers
participants to prioritize
self-care, helps to
restore hope, and
motivates to be active.

And there’s this sign of hope. That’s what I liked about the
songs.that they’re sign of hope, they’re sign of
welcoming.

It helps your day to keep going. [.] you look over at the
other person, and you see that their struggles might be a
little different than yours. But you see how they push
through it. So to me, it makes me push through it even
more because I’m like, ‘‘Okay, you know.I’m gonna
keep going.’’

Also, just learning patience with my pain and being kinder
to my body about it. In the sense of, you know, I feel like
for a long time it was mostly just being mad and having
that energy toward whatever part of my body was not
feeling good or what I couldn’t do, so I think a lot of what
I took from that was, you know, focusing on what I can do
now, what I can do to help myself, and something like
that. Yeah. I do have, I have a lot more now.

You were allowed to sing lousy or you were allowed to be
off key. [.] In the group it just didn’t matter. I watched
people’s volume—as their confidence level went up, their
volume increased. Their voices were being heard.

The songs that we would sing, it really was so motivating.
I felt like I was somewhere else.

Enhanced mind-body
connection:
VMT music experiences
and psychoeducation
help participants gain
greater awareness of the
impact of emotional and
cognitive state on their
pain management

And I think most of the benefit that I got directly from the
sessions themselves was probably for me more related to
emotional issues related with pain.

If you don’t understand your feelings, how do you expect
anyone else to? [.] this music program will help you
learn to get to know yourself. Then, other things will
follow.

When you sing, it release endorphins, so it helps to lift the
mood and better manage the pain.

(continued)

118

Integration of quantitative and qualitative findings

Participants’ reports of using music-based pain manage-
ment strategies at home aligned with the large treatment
effect for self-efficacy as the self-efficacy questionnaire
measured participants’ beliefs that they are able to control
their pain and use methods other than medication for pain
relief. Given this finding, the small improvement in pain
interference was surprising, especially since the 8-week VMT
program resulted in a moderate effect size for this outcome.

8

As for psychosocial outcomes, participants shared that they
had learned to use music to address emotions that worsen
their pain and that the VMT program had helped to develop
stronger connections with others. This was supported by the
large treatment effects for depression and participation in
social activities (i.e., ability to do things with others).

The lack of improvement in satisfaction with social roles
and activities (i.e., being able to do things for family and
friends) is explained by the qualitative findings: participants
stated that the VMT program had empowered them to set

boundaries with friends and family and prioritize self-care,
thus suggesting that ‘‘being able to do things for others’’
may not have been a desirable outcome for study partici-
pants. This makes sense given that this study included many
low-income residents with complex family situations and
high caregiver burden. Participants shared in the interviews
that self-care involves being selective with their effort in
taking care of other people.

Discussion

The purpose of this study was to determine the feasibility
and preliminary effects of a 12-week VMT program on
chronic pain management. Despite suggestions from par-
ticipants in a prior study of an 8-week version of the VMT
protocol to increase program length to 12 weeks,

8
the con-

sent rate for this study (56%) was much lower than that
obtained in the 8-week VMT study (77%). The fact that the
attrition rate in this study (23%) was lower compared with

Table 5. (Continued)

Themes and definitions Categories and definitions Example quotes

Managing emotions:
Participants learned
music-based strategies
to decrease, work
through, and tolerate
stressful and emotional
situations.

But it really showed me how if you really take the time,
music can really help with certain areas of pain. It didn’t
take away the pain completely, but I do have issues with
PTSD and anxiety and things, and I get frustrated a lot,
especially with the pain. So it taught me how to just take
that time and take a moment.

When the therapist had us doing the humming and the
singing, it made you feel at peace.

Theme 3 Developing
meaningful connections:
The VMT program
promotes social,
cultural, and spiritual
connections

Universal connection:
music experiences
promote deeper
connections with
spiritual and
metaphysical entities.

Well, it (music) is a gift from God. And God shows you
some of things that they’re (peers) going through even
though you might have been through it all ready, but that
showed them how you can come out you strong. So it was
a touching.it (music) was like a ministry thing to
me.you know, within myself.

The spiritual because I go to church. And we express
ourselves through word and dance. I kept hearing his
name. He’s the minister of music at my church. And I just
kept hearin’ him.every time she (the music therapist)
would wave that water drum or whatever that thing is
called.or somebody would hit the.whatever instrument
they would have and I’m hearing him.

Social connections:
Group music
engagement and sharing
of experiences create a
group bond, developing
deep and meaningful
relationships based on
mutual support and
learning.

Just being in a room with people and hearing their
experiences and hearing their active listening affirmations
of my experiences. We all probably have different kinds
of pain, but chronic pain is still chronic pain. Hearing and
being understood and sharing just felt real comfortable
and in a way that I had not experienced.

Being with other people that were going through similar
situations and some that had worse.[.] to know that you
weren’t the only one. ‘Cuz sometimes you can feel like
you’re alone. Especially if someone else has not
experienced what you’re feeling are. Understand where
you’re coming from.

Meeting other people, that was really good—just sit around a
bunch of people where there is no arguing, no bitterness. Just
singing and being happy at that moment and I liked that.

We’d sing like we were on the choir together. We’d
harmonize. I was like, wow! It was good. It was a joy.

PTSD, posttraumatic stress disorder.

VOCAL MUSIC THERAPY FOR CHRONIC PAIN 119

the 8-week study (27%) suggests that the length of program
negatively impacted enrollment rates, but not participants’
ability to complete the program.

Even though a higher percentage of people remained in
the study in the 12-week program, treatment adherence (i.e.,
number of sessions attended) was better in the 8-week
program (86% of the participants attended seven to eight
sessions). Yet, the interview data suggest that the VMT
program was meaningful, beneficial, and highly enjoyable
for participants in this study. Taken together, these findings
suggest that people may be more hesitant to commit to a
study or treatment program of longer duration and that
regular, weekly attendance in a 3-month program may be
more challenging due to accumulation of life- or health-
related events in a longer period of time. Indeed, childcare
issues, family emergencies, and health issues were frequently
given as reasons for missing a session.

VMT had a large treatment effect on self-efficacy. Self-
efficacy is considered a core outcome in chronic pain man-
agement as greater levels of self-efficacy have been associated
with greater physical functioning, participation in physical
activities, and performance satisfaction; enhanced health and
work status; and decreased pain intensity in people with
chronic pain.

28
Large treatment effects were also found for

depression and ability to participate in social activities. This
was supported by the interview data that indicate participants
derived a lot of joy and support from group music-making with
their peers. The experience of having chronic pain may neg-
atively impact relationships, thereby limiting social resources
for pain management. Therefore, being connected to a com-
munity or support system has been identified as an important
need of people with chronic pain.

29,30

The treatment effects between the 8- and 12-week program
were very similar, except for pain interference (Table 6). It is
unclear at this time if the difference in pain interference is a
function of treatment length or selection of outcome measure,
as a different outcome measure was used in the 12-week study.

The qualitative findings, namely enhanced pain manage-
ment, improved psychological well-being, and development
of meaningful connections, align with the biopsychosocial
framework that underlies the treatment protocol. Impor-
tantly, participants reported how active engagement in VMT
experiences facilitated these benefits inside and outside of
the session. Furthermore, creative engagement in music-
making helps people tap into their inner playfulness and
creative selves. These are important resources that, when
strengthened, may facilitate resilience in the face of life’s
challenges.

31

Creative participation also empowers people to actively take
part in their pain management, rather than feeling victimized
by pain and relying on passive pain management strategies
such as taking medicine.

8
Research increasingly finds that

active engagement in pain management enhances self-efficacy,
which can lead to improved health outcomes.

32,33
Participants

reported that learning about how their stress and emotions are
intricately linked to their physical pain, and being able to use
music-based strategies outside of the sessions to holistically
address these mind-body connections was an important treat-
ment benefit. Self-management strategies that can be easily
learned and used anywhere can lessen dependency on health
care systems and reduce health care cost.

34

This study has several limitations. The study was limited
to one urban setting that serves mostly low-income African
Americans. Furthermore, this study did not use an active
control condition. Finally, all outcome measures were self-
report and subject to bias. Based on the promising prelim-
inary treatment effects obtained in this as well as the prior
study, future research on the VMT protocol should expand
to statistically powered multisite trials that use active con-
trol conditions. Given the qualitative findings, future studies
should consider including measures of spirituality, self-care,
and empowerment. In addition, accurate measurement of
pain interference may need to be explored further, given that
participants spontaneously reported in the interviews im-
proved ability to do chores and increased physical activity,
yet, quantitatively, only a small effect size was found.

Conclusions

Both quantitative and qualitative data suggest important
benefits of VMT for chronic pain management, particularly in
the areas of self-efficacy, depression, and ability to participate
in social activities. However, feasibility data indicate that
recruitment into a 12-week VMT program for chronic pain
may be challenging. Based on the feasibility comparison of
the 8-week versus 12-week VMT protocol studies and the
fact that both programs resulted in similar treatment estimates
for core outcomes in chronic pain management, future re-
search efforts should focus on efficacy and effectiveness
testing of the 8-week version of the VMT program.

Acknowledgments

We like to express heartfelt thanks to all the people who
participated in this study. We also would like to thank the
staff and providers at Stephen and Sandra Sheller 11th Street
Family Health Services for their enthusiasm for this study

Table 6. Comparison of Treatment Effects Between 8- and 12-Week Vocal Music Therapy Program

Outcome

8-week program 12-week program

Effect size (Cohen’s d) Interpretation Effect size (Zp
2
) Interpretation

Pain-related self-efficacy 1.09 Large 0.20 Large
Pain interference 0.6 Large 0.03 Small
Pain intensity 0.46 Moderate 0.10 Moderate
Anxiety 0.39 Moderate 0.06 Moderate
Depression 0.6 Large 0.26 Large

Zp
2
, partial eta squared based on ANCOVA.

VMT, vocal music therapy.

120 LOW ET AL.

and their help with referrals. Special gratitude is extended to
Lindsay Edwards, Director of Creative Arts Therapies, for
her unwavering support for this research.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This work was supported through a cooperative agree-
ment with the National Endowment for the Arts Research
Labs program.

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Address correspondence to:
Ming Yuan Low, MA, MT-BC

Department of Creative Arts Therapies
Drexel University

1601 Cherry Street
Philadelphia, PA 19102

E-mail: [email protected]

(Appendix follows /)

VOCAL MUSIC THERAPY FOR CHRONIC PAIN 121

Appendix 1. Interview Questions

Semistructured Interview Guide

1. Can you describe your overall experience of participating in the 12-week music therapy program?
2. Did the music therapy sessions help you in any way?

In case of affirmative response:
– Can you tell me how it helped you?
In case of negative response:
– Can you give some specific reasons why the sessions were not helpful to you?
– Could you make some recommendations for changes to the music therapy program that would make it more useful

for you?
3. For patients with affirmative response continue with the following:

What about the sessions was the most helpful to you?
If patient shares a rather general response, follow-up with the following:
– Are there any specific parts of the sessions that helped you?

4. If patient did not talk about any benefits related to his/her chronic pain thus far, ask the following:
Did the music therapy sessions help you with your pain in any way?

5. Have you been using the music-based skills you learned in the sessions at home for your pain or stress management?
– In case of negative response, ask the following: What has prevented you from using these at home?

6. Were there any aspects of the sessions that did not work well for you?
In case of affirmative response, possible follow-up questions are as follows:
– Can you explain why?
– Were there any other challenges you want to share?

7. You were given materials (e.g., lyrics of songs) during the music therapy program. Did you find these materials
useful?

8. Would you recommend this program to others?
In case of affirmative response, possible follow-up question is as follows:
– How would you describe the program to them?

122 LOW ET AL.

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SPONSORED BY THE AMERICAN CANCER SOCIETY, INC.194 VOLUME 67 | NUMBER 3 | MAY/JUNE 2017

1. Highlight current practice guidelines on the use of integrative therapies during and after breast cancer treatment.
2. Apply evidence-based gradings of the efficacy of integrative treatment modalities that balance potential benefits and harms in formulating treatment decisions
and referrals for addressing the symptoms and side effects of breast cancer therapy.
3. Acknowledge the strengths and limitations of integrative therapies for treating breast cancer-related symptoms and side effects and future research needs in this area.

Clinical Practice Guidelines on the Evidence-Based Use of
Integrative Therapies During and After Breast Cancer

Treatment

Heather Greenlee, ND, PhD, MPH
1,2

; Melissa J. DuPont-Reyes, MPH, MPhil
3
; Lynda G. Balneaves, RN, PhD

4
;

Linda E. Carlson, PhD
5
; Misha R. Cohen, OMD, LAc

6,7
; Gary Deng, MD, PhD

8
; Jillian A. Johnson, PhD

9
; Matthew Mumber, MD

10
;

Dugald Seely, ND, MSc
11,12

; Suzanna M. Zick, ND, MPH
13,14

; Lindsay M. Boyce, MLIS
15

; Debu Tripathy, MD
16

Abstract: Patients with breast cancer commonly use complementary and integrative thera-
pies as supportive care during cancer treatment and to manage treatment-related side
effects. However, evidence supporting the use of such therapies in the oncology setting is
limited. This report provides updated clinical practice guidelines from the Society for Integra-
tive Oncology on the use of integrative therapies for specific clinical indications during and
after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue,
quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphede-
ma, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical prac-
tice guidelines are based on a systematic literature review from 1990 through 2015. Music
therapy, meditation, stress management, and yoga are recommended for anxiety/stress
reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for
depression/mood disorders. Meditation and yoga are recommended to improve quality of
life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced
nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-
induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the
use of ingested dietary supplements to manage breast cancer treatment-related side effects.
In summary, there is a growing body of evidence supporting the use of integrative therapies,
especially mind-body therapies, as effective supportive care strategies during breast cancer
treatment. Many integrative practices, however, remain understudied, with insufficient evi-
dence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232.
VC 2017 American Cancer Society.

Keywords: acupressure, acupuncture, breast cancer, complementary therapies, integrative
medicine, integrative oncology, massage, meditation, music therapy, stress management, yoga

Practical Implications for Continuing Education

> To make informed decisions on the use of integrative therapies in the oncology
setting, clinicians and patients should understand the level of evidence of
associated benefits and harms for each therapy.

> Based on a systematic review of the literature, the Society for Integrative
Oncology makes the following recommendations:

– Use of music therapy, meditation, stress management and yoga for anxiety/
stress reduction.

– Use of meditation, relaxation, yoga, massage and music therapy for
depression/mood disorders.

– Use of meditation and yoga to improve quality of life.

– Use of acupressure and acupuncture for reducing CINV.

– There is a lack of strong evidence supporting the use of ingested dietary
supplements or botanical agents as supportive care and/or to manage breast
cancer treatment-related side effects.

> Implementing integrative therapies in a clinical setting requires a coordinated
team approach with well-trained providers. Training and credentialing for many
integrative providers varies by jurisdictions. Best practices suggest that
providers be trained to the highest standard of their profession and educated in
other relevant disciplines.

1
Assistant Professor, Department of

Epidemiology, Mailman School of Public
Health, Columbia University, New York, NY;
2
Member, Herbert Irving Comprehensive

Cancer Center, Columbia University, New
York, NY;

3
Doctoral Fellow, Department of

Epidemiology, Mailman School of Public
Health, Columbia University, New York, NY;
4
Associate Professor, College of Nursing,

Rady Faculty of Health Sciences, Winnipeg,
MB, Canada;

5
Professor, Department of

Oncology, University of Calgary, Calgary, AB,
Canada;

6
Adjunct Professor, American

College of Traditional Chinese Medicine at
California Institute of Integral Studies, San
Francisco, CA;

7
Clinic Director, Chicken Soup

Chinese Medicine, San Francisco, CA;
8
Medical Director, Integrative Oncology,

Memorial Sloan Kettering Cancer Center,
New York, NY;

9
Post-Doctoral Scholar,

Department of Biobehavioral Health, The
Pennsylvania State University, University
Park, PA;

10
Radiation Oncologist, Harbin

Clinic, Rome, GA;
11

Executive Director,
Ottawa Integrative Cancer Center, Ottawa,
ON, Canada;

12
Executive Director of

Research, Canadian College of Naturopathic
Medicine, Toronto, ON, Canada;

13
Research

Associate Professor, Department of Family
Medicine, Michigan Medicine, University of
Michigan, Ann Arbor, MI;

14
Research

Associate Professor, Department of
Nutritional Sciences, School of Public Health,
University of Michigan, Ann Arbor, MI;
15

Research Informationist, Memorial Sloan
Kettering Library, Memorial Sloan Kettering
Cancer Center, New York, NY;

16
Professor,

Department of Breast Medical Oncology, The
University of Texas MD Anderson Cancer
Center, Houston, TX.

Additional supporting information may be
found in the online version of this article.

Corresponding author: Heather Greenlee, ND,
PhD, MPH, Department of Epidemiology, Mailman
School of Public Health, Columbia University, 722
West 168th St, Seventh Fl, New York, NY 10032;
[email protected]

DISCLOSURES: Linda E. Carlson reports book
royalties from New Harbinger and the American
Psychological Association. Misha R. Cohen
reports royalties from Health Concerns Inc.,
outside the submitted work. Matthew Mumber
owns stock in I Thrive. All remaining authors
report no conflicts of interest.

doi: 10.3322/caac.21397. Available online
at cacancerjournal.com

VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 195

CA CANCER J CLIN 2017;67:194–232

Introduction

Patients with breast cancer and breast cancer survivors are

frequent users of complementary and integrative therapies,

and there are growing numbers of formal, integrative oncol-

ogy programs within cancer centers.
1-6

Various terms are

used to describe such therapies, and it is helpful at the outset

to define terms. Complementary and alternative therapies are

generally defined as any medical system, practice, or product

that is not part of conventional medical care.7,8 Other rele-

vant terminology includes complementary medicine, which

comprises therapies used as a complement alongside

conventional medicine; alternative medicine, which com-

prises therapies used in place of conventional medicine; and

integrative medicine, which is the coordinated use of

evidence-based complementary practices and conventional

care. Integrative oncology refers to the use of complementary

and integrative therapies in collaboration with conventional

oncology care. In oncology, individuals use complementary

and integrative therapies with the intent of enhancing

wellness, improving quality of life (QOL), and relieving

symptoms of disease and side effects of conventional treat-

ments. However, the evidence supporting the use of

complementary and integrative therapies in the oncology

setting is limited.

In November 2014, the Society for Integrative Oncology

(SIO) published clinical practice guidelines to inform both

clinicians and patients on the use of integrative therapies

during breast cancer treatment and to treat breast cancer

treatment-related symptoms.9 The SIO adapted methods

established by the US Preventive Services Task Force10 to

develop graded recommendations on the use of specific inte-

grative therapies for defined clinical indications based on

the strength of available evidence concerning associated

benefits and harms. The 2014 clinical practice guidelines

were derived from a systematic review of randomized clini-

cal trials published between 1990 and 2013 and organized

by specific clinical conditions (eg, anxiety/stress, fatigue).

This review provides an updated set of clinical practice

guidelines based on a current, systematic literature review of

randomized controlled trials (RCTs) published through

December 2015 along with detailed definitions of integra-

tive therapies and clinical outcomes of interest, a detailed

summary of the literature upon which the clinical practice

guidelines are based, and suggestions for how appropriate

therapies may be integrated into clinical practice.

Of note, it is important to define the use of the term rec-

ommendation in these clinical practice guidelines. In many

settings, a clinical guideline recommendation suggests that it

should be used as the standard of care and is favorable or

equal compared with all other options based on best clinical

evidence for benefit/risk ratio. Here, in the setting of inte-

grative oncology, we use the term recommendation to

conclude that the therapy should be considered as a viable

but not singular option for the management of a specific

symptom or side effect. Few studies have conducted a head-

to-head comparison of a given integrative therapy against a

conventional treatment, and most integrative therapies are

used in conjunction with standard therapy and have been

studied in this manner. Moreover, combination-based

approaches and the interactions of the numerous permuta-

tions of integrative and conventional treatments have not

been formally investigated, such that recommendations must

account for this limitation of our knowledge. Despite these

limitations to evaluating the use of integrative therapies in

the oncology setting, there is a body of well conducted trials

of specific therapies for specific conditions that provides suf-

ficient evidence to warrant recommendations on the thera-

pies as viable options for treating specific conditions.

In this review, we provide clinicians and patients with

updated SIO clinical practice guidelines on the use of inte-

grative therapies to manage symptoms and side effects during

and after breast cancer treatment. The clinical practice guide-

lines do not address breast cancer recurrence or survival end-

points, because very few adequately powered RCTs have

examined the effect of integrative therapies on these out-

comes. We also provide a definition for each integrative ther-

apy that had a sufficiently large body of evidence to formulate

a specific recommendation. Information is also provided on

how to implement the recommendations into the clinical set-

ting, with caveats for specific clinical situations. In addition,

this review summarizes pertinent meta-analyses and identifies

promising areas for future investigation. The information

that arose from other published reviews and meta-analyses

did not change the interpretation of the findings or the quali-

ty of specific trials, but the information was used to influence

the establishment of specific recommendation grades based

on consistency, reproducibility, and assessment of potential

harms and benefits. The goal of this current review is to pro-

vide clinicians and patients with practical information and

tools to evaluate whether there is an evidence base to support

the use of a defined integrative therapy for a specific clinical

application in the context of breast cancer.

Methods

Systematic Review Methodology

To update the previously published clinical practice guide-

lines, which were based on a systematic review of the litera-

ture from January 1, 1990 through December 31, 2013,
9

we

conducted a systematic review of published RCTs from Jan-

uary 1, 2014 through December 31, 2015, using the same

search criteria and process. The process followed the meth-

ods set forth by the Institute of Medicine on clinical guide-

line development.
11

The following databases were searched:

Embase, MEDLINE, PsychINFO, and CINAHL.

Integrative Therapies During and After Breast Cancer Treatment

196 CA: A Cancer Journal for Clinicians

As previously reported,9 trials were selected for inclusion in

the systematic review if they met the following criteria:

1) peer-reviewed, published RCT; 2) available in English;

3) included �50% patients with breast cancer and/or
reported results separately for patients with breast cancer;

4) used an integrative therapy as an intervention during stan-

dard treatment with surgery, chemotherapy, radiation thera-

py, and/or hormonal therapy or addressed symptoms and

side effects resulting from diagnosis and/or treatment; and

5) addressed an endpoint of clinical relevance to patients

with breast cancer and breast cancer survivors (see Support-

ing Information Table 1).9 Several lifestyle and psychological

interventions were excluded from current as well as previous

guidelines, because they have already been well summarized

by other groups (eg, diet
12,13

and physical activity
12-14

rec-

ommendations for cancer survivors) and/or because they

have a strong evidence base and are often considered to be

mainstream rather than integrative or complementary (eg,

cognitive-behavioral therapy,
15

psychoeducation,
16

counsel-

ing,
17

and support groups
16

). Other interventions that were

excluded were in early or pilot stages of research (eg,

attention-restoration therapy) or were not considered to be

an integrative oncology therapy for the purposes of the SIO

guidelines (eg, prayer, spirituality). Each article was scored

according to the quality of design and reporting based on the

Jadad scoring scale and a modified scale adapted from the

Delphi scoring system.18,19 Finally, grades of evidence were

determined for each therapy as applied to a specific clinical

outcome using a modified version of the US Preventive Serv-

ices Task Force grading system.
10

Grades were based on

strength of evidence, determined by the number of trials,

quality of trials, magnitude of effect, statistical significance,

sample size, consistency of results across studies, and whether

the outcomes were primary or secondary. The highest grades

(A and B) indicate that a specific therapy is recommended for

a particular clinical indication. Grade A indicates there is

high certainty that the net benefit is substantial, while grade

B indicates there is high certainty that the net benefit is mod-

erate or there is moderate certainty that the net benefit is

moderate to substantial. Grade C indicates that the evidence

is equivocal or that there is at least moderate certainty that

the net benefit is small. The lowest grades (D, H, and I) indi-

cate no demonstrated effect, suggest harm, or indicate that

the current evidence is inconclusive, respectively.

According to the clinical guideline development process

outlined by the Institute of Medicine,11 drafts prepared by

the SIO Guideline Working Group were distributed to an

interdisciplinary group of SIO internal and external reviewers.

Reviewer comments, suggestions, and critiques were incorpo-

rated into the final version of these guidelines.

It is important to note that, as we reviewed the literature,

we recognized the difference between statistical and

clinical significance. The graded recommendations reflect

our assessment of the clinical significance based on our

assessment of the body of literature, including the impor-

tance of statistical significance with respect to the primary

endpoint. We did not report on specific magnitudes of

effect because of the range of outcome measures and statisti-

cal methods used across the trials, which made it difficult to

describe detailed data on effect sizes across all trials.

Although some of the trials with small sample sizes (n <

100) may have been methodologically sound, we down-

played their contribution to the graded recommendation,

because larger trials provided more information on general-

izability of results to larger populations. Because of space

limitations, P values are reported and citations are provided

to reference the primary reports for additional details.

Definitions of Complementary and Integrative
Therapies

Below are definitions listed alphabetically for each of the

complementary and integrative therapies that received

a grade of A, B, C, D, or H in the updated clinical

practice guidelines.20,21 Table 1 displays the graded rec-

ommendations.
10,22-151

Table 2 provides background

information on the specific training, licensure, and profes-

sional organizations associated with each therapy.152 If a

therapy is known to have a specific contraindication or

caution, it is noted in the description. The descriptions

include statements on how the therapies are often used by

patients with cancer and by survivors but do not indicate

the level of evidence supporting such use. The guideline

recommendations provide a summary of the evidence on

the use for specific conditions. In addition to the informa-

tion provided below, there are continuously updated, well

referenced websites that can provide additional details on

the range of therapies, including Natural Medicines (nat-

uralmedicines.therapeuticresearch.com), Memorial Sloan

Kettering Cancer Center’s About Herbs website (mskcc.org/

cancer-care/treatments/symptom-management/integrative-

medicine/herbs), and the National Cancer Institute (NCI)

Office of Cancer Complementary and Alternative Medicine

Therapies: A-Z website (cam.cancer.gov/health_informa-

tion/cam_therapies_a-z.htm).

Acetyl-L-carnitine

Acetyl-L-carnitine is a dietary supplement that some

patients use to treat cancer-related fatigue by enhancing

energy and lowering inflammation in the body.
153

It has

demonstrated effectiveness in preventing and treating dia-

betic neuropathy and thus was of interest to examine in the

context of chemotherapy-induced peripheral neuropathy

(CIPN). It is a substance made in muscle and liver tissue

and is found in foods, including meats, poultry, fish, and

some dairy products.

CA CANCER J CLIN 2017;67:194–232

VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 197

TABLE 1. Graded Integrative Therapies for Use in Patients With Breast Cancer According to Clinical Outcomes
a

CLINICAL
OUTCOMES RECOMMENDED THERAPY

STRENGTH OF
EVIDENCE GRADEb

Acute radiation
skin reaction

Aloe vera22,23 and hyaluronic acid cream24,25 should not be recommended for improving acute
radiation skin reaction.

D

Anxiety/stress reduction Meditation is recommended for reducing anxiety.26-30 A

Music therapy is recommended for reducing anxiety.31-35 B

Stress management is recommended for reducing anxiety during treatment, but longer group
programs are likely better than self-administered home programs or shorter programs.36-39

B

Yoga is recommended for reducing anxiety.40-48 B

Acupuncture,49-51 massage,52-55 and relaxation56-60 can be considered for reducing anxiety. C

Chemotherapy-induced
nausea and vomiting

Acupressure can be considered as an addition to antiemetics drugs to control nausea and
vomiting during chemotherapy.61-63

B

Electroacupuncture can be considered as an addition to antiemetics drugs to control vomiting
during chemotherapy.64,65

B

Ginger66-68 and relaxation59,69 can be considered as additions to antiemetic drugs to control
nausea and vomiting during chemotherapy.

C

Glutamine70,71 should not be recommended for improving nausea and vomiting during
chemotherapy.

D

Depression/mood
disturbance

Meditation, particularly MBSR, is recommended for treating mood disturbance and depressive
symptoms.26-30,72-76

A

Relaxation is recommended for improving mood disturbance and depressive
symptoms.56,59,60,69,77,78

A

Yoga is recommended for improving mood and depressive symptoms.40-43,45-48,79-85 B

Massage is recommended for improving mood disturbance.53-55,86-88 B

Music therapy is recommended for improving mood.33,35,89,90 B

Acupuncture,49-51,91,92 healing touch,93,94 and stress management36-38,95,96 can be considered
for improving mood disturbance and depressive symptoms.

C

Fatigue Hypnosis97,98 and ginseng99,100 can be considered for improving fatigue during treatment. C

Acupuncture51,101-103 and yoga45,80,84,104-106 can be considered for improving post-treatment
fatigue.

C

Acetyl-L-carnitine107 and guarana108,109 should not be recommended for improving fatigue
during treatment.

D

Lymphedema Low-level laser therapy,110,111 manual lymphatic drainage,112-118 and compression bandag-
ing114-116 can be considered for improving lymphedema.

C

Neuropathy Acetyl-L-carnitine is not recommended for the prevention of chemotherapy-induced peripheral
neuropathy in patients with BC due to potential harm.107

H

Pain Acupuncture,119-124 healing touch,93 hypnosis,125,126 and music therapy31,34 can be considered
for the management of pain.

C

Quality of life Meditation is recommended for improving quality of life.27-29,73-75,127 A

Yoga is recommended for improving quality of life.43,46-48,82-85,104-106,128 B

Acupuncture,49,51,102,129,130 mistletoe,131-134 qigong,135,136 reflexology,137-139 and stress
management36-38,95,96,140,141 can be considered for improving quality of life.

C

Sleep disturbance Gentle yoga45,48,79,84,142 can be considered for improving sleep. C

Vasomotor/hot flashes Acupuncture49,91,92,143-148 can be considered for improving hot flashes. C

Soy149-151 is not recommended for hot flashes in patients with BC due to lack of effect. D

Abbreviations: BC, breast cancer; MBSR, mindfulness-based stress reduction.
a
The clinical population is patients with BC during treatment, including surgery,

chemotherapy, hormonal/biological therapy, and radiation therapy. The clinical question is “What integrative therapies can be used to prevent, treat and man-
age symptoms and side effects encountered during breast cancer treatment?”

b
Definitions of the grade of recommendations are as follows

10
: Grade A recom-

mends the modality (there is high certainty that the net benefit is substantial: offer/provide this modality). Grade B recommends the modality (there is high
certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial: offer/provide this modality). Grade C
recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences (there is at least mod-
erate certainty that the net benefit is small: offer/provide this modality for selected patients, depending on individual circumstances). Grade D recommends
against the service (there is moderate or high certainty that the modality has no net benefit: discourage the use of this modality). Grade H recommends
against the service (there is moderate or high certainty that the harms outweigh the benefits: discourage the use of this modality).

Integrative Therapies During and After Breast Cancer Treatment

198 CA: A Cancer Journal for Clinicians

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,

th
er

e
ar

e
no

ac
cr

ed
it

ed
sc

ho
o
ls

o
ff

er
in

g
st

an
da

rd
co

lle
ge

o
r

un
iv

er
si

ty
de

gr
ee

s
in

hy
pn

o
si

s;
th

er
ef

o
re

,
tr

ai
ni

ng
in

o
ne

o
f

th
e

ab
o
ve

pr
o
fe

ss
io

ns
is

ty
pi

ca
lly

re
qu

ir
ed

be
fo

re
ac

ce
pt

an
ce

in
to

o
ne

o
f

m
an

y
tr

ai
ni

ng
o
r

ce
rt

if
ic

at
io

n
pr

o
gr

am
s.

Th
es

e
pr

o
gr

am
s

ha
ve

a
w

id
e

ra
ng

e
o
f

tr
ai

ni
ng

re
qu

ir
em

en
ts

bu
t

in
ge

ne
ra

l
re

qu
ir

e
an

yw
he

re
fr

o
m

5
0

to
2

0
0

h
o
f

cl
as

sr
o
o
m

an
d

cl
in

ic
al

tr
ai

ni
ng

be
fo

re
ce

rt
if
ic

at
io

n.

U
N

IT
ED

ST
A

TE
S:

To
be

ce
rt

if
ie

d
as

a
cl

in
ic

al
hy

pn
o
th

er
ap

is
t,

ap
pl

ic
an

ts
ty

pi
ca

lly
re

qu
ir

e
an

yw
he

re
fr

o
m

5
0

to
2

0
0

h
o
f

tr
ai

ni
ng

an
d

o
ft

en
y

o
f

ex
pe

ri
en

ce
.

Th
er

e
ar

e
a

nu
m

be
r

o
f

ce
rt

if
ic

at
io

n
pr

o
gr

am
s

w
it

h
a

ra
ng

e
o
f

re
qu

ir
em

en
ts

(s
ee

lin
ks

).
R

eg
ul

at
io

ns
fo

r
th

e
pr

ac
ti

ce
o
f

hy
pn

o
si

s
va

ry
o
n

a
st

at
e-

by
-s

ta
te

ba
si

s
(a

ih
cp

.o
rg

/h
yp

no
si

s-
re

gu
la

ti
o
n.

ht
m

).
Ty

pi
ca

lly
,

cl
in

ic
al

hy
pn

o
th

er
ap

is
ts

m
us

t
re

ne
w

th
ei

r
ce

rt
if
ic

at
io

n
ev

er
y

2
to

4
y

an
d

m
us

t
ha

ve
co

m
pl

et
ed

2
0
1

h
o
f

ap
pr

o
ve

d
tr

ai
ni

ng
du

ri
ng

th
at

ti
m

e.

C
A

N
A

D
A

:
C

er
ti

fi
ca

ti
o
n

is
si

m
ila

r
to

th
e

U
ni

te
d

St
at

es
;

ho
w

ev
er

,
re

qu
ir

em
en

ts
ar

e
m

uc
h

hi
gh

er
,

be
tw

ee
n

2
2

5
an

d
1

1
0

0
h

(a
rc

hc
a-

na
da

.c
a/

).

Th
e

C
o
un

ci
l

o
f

Pr
o
fe

ss
io

na
l

H
yp

no
si

s
en

co
m

pa
ss

es
m

an
y

pr
o
fe

s-
si

o
na

l
so

ci
et

ie
s

an
d

o
rg

an
iz

at
io

ns
lis

te
d

(c
o
ph

o
.c

o
m

/o
rg

.h
tm

).

A
ss

o
ci

at
io

n
o
f

R
eg

is
te

re
d

C
lin

ic
al

H
yp

no
th

er
ap

is
ts

(A
R

C
H

),
ar

ch
–

ca
na

da
.c

a/
;

A
m

er
ic

an
C

o
lle

ge
o
f

H
yp

no
th

er
ap

y
at

th
e

A
m

er
ic

an
In

st
itu

te
of

H
ea

lth
C

ar
e

Pr
of

es
si

on
al

s,
ai

hc
p.

ne
t/

am
er

ic
an

-c
ol

le
ge

-o
f-

hy
pn

ot
he

ra
py

/;
A

m
er

ic
an

So
ci

et
y

of
C

lin
ic

al
H

yp
no

si
s

(A
SC

H
),

as
ch

.
ne

t/
;

H
yp

no
si

s
M

ot
iv

at
io

n
In

st
it
ut

e
(H

M
I),

hy
pn

os
is

.e
du

;
N

at
io

na
l

B
oa

rd
fo

r
C

er
tif

ie
d

C
lin

ic
al

H
yp

no
th

er
ap

is
ts

(N
B

C
C

H
),

na
tb

oa
rd

.
co

m
;

Th
e

In
te

rn
at

io
na

l
So

ci
et

y
of

H
yp

no
si

s
(IS

H
),

is
hh

yp
no

si
s.

or
g/

;
So

ci
et

y
fo

r
C

lin
ic

al
an

d
Ex

pe
rim

en
ta

l
H

yp
no

si
s

(S
C

EH
),

sc
eh

.u
s/

;
Th

e
M

ilt
on

H
.

Er
ic

ks
on

Fo
un

da
tio

n,
er

ic
ks

on
-f

ou
nd

at
io

n.
or

g/

M
as

sa
ge

A
ss

o
ci

at
ed

B
o
dy

w
o
rk

an
d

M
as

sa
ge

Pr
o
fe

ss
io

na
l

(A
B

M
P)

m
em

be
rs

at
th

e
ce

rt
if
ie

d
o
r

pr
o
fe

ss
io

na
l

le
ve

ls
m

us
t

po
ss

es
s

a
va

lid
m

as
–

sa
ge

lic
en

se
fr

o
m

a
re

gu
la

te
d

st
at

e/
pr

o
vi

nc
e/

te
rr

it
o
ry

,
m

us
t

ha
ve

co
m

pl
et

ed
5

0
0

ap
pr

o
ve

d
ed

uc
at

io
na

l
h

o
r

be
ce

rt
if
ie

d
th

ro
ug

h
th

e
N

at
io

na
l

C
er

ti
fi
ca

ti
o
n

B
o
ar

d
fo

r
Th

er
ap

eu
ti

c
M

as
sa

ge
an

d
B

o
dy

w
o
rk

(N
C

TM
B

).
Li

ce
ns

ed
nu

rs
e

an
d

ph
ys

ic
al

th
er

ap
is

ts
m

ay
qu

al
if
y

fo
r

m
em

be
rs

hi
p

at
ei

th
er

th
e

ce
rt

if
ie

d
o
r

pr
o
fe

ss
io

na
l

le
ve

l
w

it
h

a
m

in
im

um
o
f

5
0

h
o
f

ad
di

ti
o
na

l
m

as
sa

ge
th

er
ap

y
tr

ai
ni

ng
.

B
o
ar

d
ce

rt
if
ic

at
io

n
is

th
e

hi
gh

es
t

vo
lu

nt
ar

y
cr

ed
en

ti
al

at
ta

in
ab

le
to

m
as

sa
ge

th
er

ap
is

ts
an

d
bo

dy
w

or
ke

rs
in

th
e

pr
o
fe

ss
io

n
to

da
y

(f
o
r

th
e

re
qu

ir
em

en
ts

o
f

bo
ar

d
ce

rt
if
ic

at
io

n,
se

e
nc

bt
m

b.
o
rg

/
bo

ar
d-

ce
rt

if
ic

at
io

n)
.

U
N

IT
ED

ST
A

TE
S:

M
as

sa
ge

th
er

ap
y

is
re

gu
la

te
d

by
so

m
e

U
S

st
at

es
.

Se
e

lin
k

fo
r

st
at

e-
by

-s
ta

te
m

as
sa

ge
lic

en
su

re
in

fo
rm

at
io

n
(m

as
sa

ge
th

er
ap

y.
co

m
/c

ar
ee

rs
/s

ta
te

bo
ar

ds
.p

hp
).

C
A

N
A

D
A

:
M

as
sa

ge
th

er
ap

is
ts

ca
n

o
nl

y
be

re
gi

st
er

ed
,

no
t

lic
en

se
d,

in
C

an
ad

a.
C

ur
re

nt
ly

,
o
nl

y
4

pr
o
vi

nc
es

re
gu

la
te

m
as

sa
ge

th
er

ap
is

ts
:

O
nt

ar
io

,
B

ri
ti

sh
C

o
lu

m
bi

a,
N

ew
B

ru
ns

w
ic

k,
an

d
N

ew
fo

un
dl

an
d.

Th
e

W
eb

si
te

fo
r

th
e

O
nt

ar
io

M
as

sa
ge

Th
er

ap
is

ts
ha

s
lin

ks
to

th
e

4
pr

o
vi

nc
es

’
re

gi
st

ra
ti

o
n

pr
o
ce

du
re

s
an

d
lin

ks
to

o
th

er
pr

o
vi

nc
ia

l
m

as
sa

ge
o
rg

an
iz

at
io

ns
.

A
m

er
ic

an
M

as
sa

ge
Th

er
ap

y
A

ss
o
ci

at
io

n,
am

ta
m

as
sa

ge
.o

rg
;

A
B

M
P,

ab
m

p.
co

m
;

N
C

TM
B

,
nc

bt
m

b.
o
rg

/;
So

ci
et

y
fo

r
O

nc
o
lo

gy
M

as
sa

ge
,

s4
o
m

.o
rg

/

M
as

sa
ge

Th
er

ap
is

ts
’

A
ss

o
ci

at
io

n
o
f

O
nt

ar
io

,
se

cu
re

.r
m

ta
o
.c

o
m

/
m

as
sa

ge
_

th
er

ap
y/

re
gu

la
tio

n_
of

_
m

t/
m

as
sa

ge
_

th
er

ap
y_

in
_

ca
na

da
.

ht
m

CA CANCER J CLIN 2017;67:194–232

VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 199

T
A

B
L
E

2
.

C
o

n
ti

n
u

e
d

M
O

D
A

LI
T
Y

O
R

T
H

E
R

A
P
Y

T
R

A
IN

IN
G

LI
C

E
N

S
U

R
E

A
N

D
R

E
G

U
LA

T
IO

N
P
R

O
FE

S
S
IO

N
A

L
S
O

C
IE

T
IE

S
A

N
D

O
R

G
A

N
IZ

A
T
IO

N
S

M
ed

it
at

io
n

M
in

df
ul

ne
ss

-B
as

ed
St

re
ss

R
ed

uc
ti

o
n:

Th
e

C
en

te
r

fo
r

M
in

df
ul

ne
ss

in
M

as
sa

ch
us

et
ts

pr
o
vi

de
s

m
ed

it
at

io
n

sp
ec

ia
lis

t
tr

ai
ni

ng
(u

m
as

sm
ed

.e
du

/c
fm

/t
ra

in
in

g/
de

ta
ile

d-
tr

ai
ni

ng
-i

nf
o
rm

at
io

n/
te

ac
he

r-
ce

rt
if
ic

at
io

n-
re

vi
ew

/)
.

In
bo

th
th

e
U

ni
te

d
St

at
es

an
d

C
an

ad
a,

bo
ar

d
ce

rt
if
ic

at
io

n
is

th
e

hi
gh

es
t

cr
ed

en
ti

al
at

ta
in

ab
le

fo
r

m
ed

it
at

io
n

te
ac

he
rs

in
th

e
he

al
th

ca
re

pr
o
fe

ss
io

n
to

da
y.

Th
er

e
is

no
re

gi
st

ra
ti

o
n

o
r

lic
en

su
re

cu
rr

en
tl

y
av

ai
la

bl
e.

A
m

er
ic

an
M

in
df

ul
ne

ss
R

es
ea

rc
h

A
ss

o
ci

at
io

n,
go

am
ra

.o
rg

/

Th
e

U
ni

ve
rs

it
y

o
f

C
al

if
o
rn

ia
at

Sa
n

D
ie

go
C

en
te

r
fo

r
M

in
df

ul
ne

ss
pr

o
vi

de
s

ex
te

ns
iv

e
tr

ai
ni

ng
(m

bp
ti

.o
rg

/)
.

Th
e

U
ni

ve
rs

it
y

o
f

B
an

go
r

in
W

al
es

aw
ar

ds
a

M
as

te
rs

in
M

in
df

ul
–

ne
ss

an
d

al
so

ha
s

a
ra

ng
e

o
f

te
ac

he
r

tr
ai

ni
ng

pr
o
gr

am
s

(b
an

go
r.

ac
.u

k/
m

in
df

ul
ne

ss
/c

o
ur

se
s.

ph
p.

en
)

Th
e

C
en

tr
e

fo
r

M
in

df
ul

ne
ss

St
ud

ie
s

in
To

ro
nt

o
,

O
nt

ar
io

,
C

an
ad

a,
o
ff

er
s

1
-d

w
o
rk

sh
o
ps

as
w

el
l

as
in

te
ns

iv
e

pr
o
fe

ss
io

na
l

tr
ai

ni
ng

in
M

in
df

ul
ne

ss
-B

as
ed

C
o
gn

it
iv

e
Th

er
ap

y
(m

in
df

ul
ne

ss
st

ud
ie

s.
co

m
/)

.

C
o
m

pl
et

in
g

m
in

df
ul

ne
ss

te
ac

he
r

tr
ai

ni
ng

co
ur

se
s

at
o
ne

o
f

th
e

re
co

gn
iz

ed
tr

ai
ni

ng
pr

o
gr

am
s,

in
ad

di
ti

o
n

to
pr

o
fe

ss
io

na
l

ce
rt

if
ic

at
io

n,
w

o
ul

d
be

th
e

o
pt

im
al

le
ve

l
o
f

tr
ai

ni
ng

fo
r

pr
o
vi

di
ng

th
es

e
in

te
rv

en
ti

o
ns

.

M
us

ic
th

er
ap

y
A

pr
o
fe

ss
io

na
l

m
us

ic
th

er
ap

is
t

ho
ld

s
a

ba
ch

el
o
r’

s
de

gr
ee

o
r

hi
gh

er
in

m
us

ic
th

er
ap

y
fr

o
m

o
ne

o
f

o
ve

r
7

0
A

m
er

ic
an

M
us

ic
Th

er
ap

y
A

ss
o
ci

at
io

n-
ap

pr
o
ve

d
co

lle
ge

an
d

un
iv

er
si

ty
pr

o
gr

am
s.

M
us

ic
th

er
ap

is
ts

w
ho

cu
rr

en
tl

y
ho

ld
pr

o
fe

ss
io

na
l

de
si

gn
at

io
n

ar
e

lis
te

d
o
n

th
e

N
at

io
na

l
M

us
ic

Th
er

ap
y

R
eg

is
tr

y
an

d
ar

e
qu

al
if
ie

d
to

pr
ac

ti
ce

m
us

ic
th

er
ap

y.

M
us

ic
th

er
ap

is
ts

ar
e

re
gu

la
te

d
by

so
m

e
U

S
st

at
es

(e
g,

N
o
rt

h
D

ak
o
ta

,
N

ev
ad

a;
fo

r
st

at
e-

by
-s

ta
te

m
as

sa
ge

lic
en

su
re

in
fo

rm
at

io
n,

se
e

cb
m

t.
o
rg

/e
xa

m
in

at
io

n/
st

at
e-

lic
en

su
re

/)
.

C
ur

re
nt

ly
no

C
an

ad
ia

n
pr

o
vi

nc
es

/t
er

ri
to

ri
es

lic
en

se
o
r

re
gu

la
te

m
us

ic
th

er
ap

is
ts

.

Th
e

C
er

ti
fi
ca

ti
o
n

B
o
ar

d
fo

r
M

us
ic

Th
er

ap
is

ts
(C

B
M

T)
,

cb
m

t.
o
rg

/;
C

an
ad

ia
n

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Integrative Therapies During and After Breast Cancer Treatment

200 CA: A Cancer Journal for Clinicians

Acupuncture

Acupuncture involves the stimulation of specific points, (ie,

acupoints) by penetrating the skin with thin, solid, metallic

needles.154,155 A variation of acupuncture includes electro-

acupuncture, in which a small electric current is passed

along acupuncture needles to provide a stronger stimulus

than acupuncture alone, with distinct effects suggested by

functional magnetic resonance imaging.156,157 Acupuncture

has been practiced in Asia for thousands of years as a com-

ponent of traditional medicine systems (eg, traditional forms

of Chinese, Japanese, and Korean medicine) and is thought

to stimulate the flow of a form of energy called qi (chee)

throughout the body. Traditional Chinese acupuncture,

which is commonly used in North America, requires needle

manipulation to produce a de qi sensation (a soreness, full-

ness, heaviness, or local area distension157,158), along with a

period of rest with the needles in place.
159

It is posited that

this removes energetic blockages, thus reestablishing

homeostasis. The mechanisms for acupuncture’s effects are

not well understood but are thought to function in part

through modulation of specific neuronal/cortical path-

ways.
160

Acupuncture practice typically requires formal edu-

cation through schools, training programs, and certifications

(Table 2). Acupuncture is often used in the oncology setting

for chemotherapy-induced nausea/vomiting (CINV), pain

management, musculoskeletal complaints, hot flashes,

fatigue, stress, anxiety, and sleep disorders. The practice of

acupuncture in North America is regulated by some US

states and Canadian provinces and territories (Table 2).

Acupressure

Acupressure draws on the same knowledge and philosophi-

cal system as acupuncture. A trained therapist or the patient

uses his/her hands and fingers, or possibly a device, to apply

pressure to specific points on the body (acupoints), in con-

trast to metallic needles.161 Practices can range from stimu-

lating a single point or a combination of points to achieve

the intended outcome. In the oncology setting, acupressure

is often used for CINV pain, stress management, and

fatigue.

Aloe vera

Aloe vera gel is derived from the leaves of the perennial suc-

culent plant, Aloe vera (Liliaceae). Typically, it is applied

topically or ingested in the form of a clear, thick gel.153

Aloe vera gel is found in multiple skin products, such as

lotions, creams, and sunblock, and is used as a topical oint-

ment to heal wounds, sunburn, insect bites, and skin condi-

tions, including psoriasis and frostbite.162 In oncology, it is

typically used with the goal of healing surgical wounds or

preventing or treating radiation-induced dermatitis.

Ginger

Ginger (Zingiber officianale) comes from the rhizome or

root of a tropical plant with green-purple flowers and an

aromatic stem.153,163 Ginger can be used as a food in cook-

ing and for medicinal purposes. In Asian medicine, ginger is

used to treat stomach aches, nausea, and diarrhea. For

patients with cancer, it has been studied for the treatment

of CINV. Ginger is available in capsule form, fresh as a

root, as a tea, as a candy, or at highly diluted quantities in

ginger ale. Ginger supplementation should not be used in

perioperative settings or in patients with bleeding disorders

due to a potential risk of increased bleeding.
162

Ginseng

Ginseng is derived from a plant root and has been used to

treat certain medical problems.
153

Two common types of

ginseng are used: Asian ginseng (Panax ginseng) and Ameri-

can ginseng (Panax quinquefolius). Another herb called

Siberian ginseng or eleuthero is not a true ginseng.162 Asian

and American ginsengs are used to boost the immune sys-

tem and promote well being and stamina. Ginseng comes in

capsule form made of ground ginseng, extracts, and teas and

in creams and other products for topical use. Taken as an

herbal supplement, ginseng is often used to treat cancer-

related fatigue.162 Side effects of taking ginseng may include

headaches, breast tenderness and menstrual irregularities,

sleep problems, restlessness, rapid heart rate, low blood sug-

ar, allergic reactions, and gastrointestinal problems.162

Glutamine

Glutamine is a nonessential amino acid used in the biosyn-

thesis of proteins and is primarily synthesized in skeletal

muscle.162 Most of the glutamine synthesized in the body is

used by the intestinal tract. Glutamine has numerous bio-

logic functions, including protein and lipid synthesis and

the regulation of acid-base balance in the kidney, and it is

an important mitochondrial cellular energy source. Normal-

ly, the body can synthesize its own glutamine; however, dur-

ing a critical illness like cancer, not enough glutamine is

made, leading to problems such as fatigue and muscle wast-

ing. Glutamine has been used as an oral supplement in

patients with cancer to reverse cachexia in those who have

advanced disease. It has also been used for CINV in patients

with cancer. Glutamine can be obtained from food or sup-

plements, and important food sources include beef, pork,

chicken, fish, eggs, milk, dairy products, wheat, cabbage,

beets, beans, spinach, and parsley.
162

Guarana

Guarana is an herbal supplement from the guarana plant

(Paullinia cupana), which is native to the Amazon basin.162

Guarana supplements contain various phytochemicals,

including caffeine, theobromine, theophylline, tannins, sap-

onins, catechins, epicatechins, proanthocyanidols, and other

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compounds, in minor concentrations. Guarana has been

used as a stimulant since pre-Columbian times.
162

In the

oncology setting, guarana is often used to decrease fatigue.

Healing touch

Healing touch (also known as therapeutic touch) is based on

the belief that vital energy flows through and around the

human body and may be transferred or modified.
93,94

A

healing touch practitioner (often a nurse trained in the prac-

tice) passes his/her hands over, or gently touches, a patient’s

body to balance or increase their energy. Healing touch is

often used in patients with cancer to improve QOL, pain,

fatigue, and depression.

Hyaluronic acid cream

Hyaluronic acid cream is a topical cream containing hyalur-

onic acid that is used to heal wounds through repair-

promoting, skin-moisturizing, and potential radioprotective

properties.153 When the cream is applied, the hyaluronic

acid adheres to injured tissue, provides hydration to the

skin, and protects against dehydration and chemical and

mechanical irritation. Hyaluronic acid cream is often used

by patients with cancer to prevent and treat radiation-

induced dermatitis.

Hypnosis

Hypnosis is facilitated by a specially trained therapist or is

practiced on one’s own (self-hypnosis). It is characterized by

a trance-like state, which allows a patient to be more aware,

focused, and open to suggestion. A person in a hypnotic

state can concentrate more clearly on specific feelings,

thoughts, images, sensations, or behaviors without distrac-

tion.164 The hypnotic state is obtained by first relaxing the

body and then shifting attention toward a narrow range of

objects or ideas given by the hypnotist or hypnotherapist. A

person under hypnosis may feel more calm and relaxed. In

patients with cancer, hypnosis is often used to help relieve

stress, anxiety, and pain.

Laser therapy

Low-level laser therapy has been cleared by the FDA to

treat lymphedema after breast cancer surgery
165

and should

be administered by trained users. It is believed that low-level

laser therapy stimulates macrophages and the immune sys-

tem and breaks down scar tissue, thus improving lymphatic

flow.166

Manual lymphatic drainage and compression bandaging

Manual lymphatic drainage and compression bandaging are

used individually and in combination for the treatment of

lymphedema after breast cancer surgery.166 Manual lymph

drainage is a specific type of therapeutic massage that ideally

is delivered by a health professional who is certified in the

technique. Manual lymph drainage can decrease lymphede-

ma when administered early, before symptoms advance.
166

Compression bandages or garments, including sleeves,

stockings, bras, compression shorts, gloves, bandages, or

neck compression wraps, are also used to treat lymphedema

and can be worn during the day or night, depending on the

garment and the individual.166

Massage

There are many different forms of this type of physical ther-

apy, which involves a therapist stroking, kneading, applying

friction, and stretching specific muscles and other connec-

tive tissues at an even tempo with various levels of pres-

sure.
167

In patients with cancer, the goal of massage is to

promote relaxation, address muscle stiffness and pain, and

resolve musculoskeletal complaints. There are multiple

forms of massage, including, but not limited to, Swedish,

Shiatsu, and deep-tissue massage. Massage therapists should

take precautions with all patients who have cancer and to

avoid massaging specific vulnerable areas of the body,

including open wounds, bruises, skin breakdown, a blood

clot in a vein, a tumor site, areas near a medical device (eg,

drain), or sensitive skin after radiation therapy.
168

In addi-

tion, certain patients with multiple bone metastases may be

at risk for fracture during deep massage. The practice of

massage therapy in North America is regulated by some US

states and Canadian provinces and territories (Table 2).

Meditation

Meditation is a group of self-regulation practices focused on

training attention and awareness to bring mental processes

under greater voluntary control.169 In patients with cancer,

these practices are intended to foster general mental well

being, calmness, clarity, and concentration. The ultimate

goal of meditation varies, depending on the type of practice,

its history, and its application. Most meditation practices

have 4 elements in common: a quiet location with few dis-

tractions; a specific, comfortable posture achieved by sitting

or lying down; a focus of attention; and an open attitude of

letting thoughts come and go naturally without judg-

ment.170 The focus of attention may be on a specific target,

such as the breath or a repeated sound or mantra (known as

concentration meditation); on all experiences that enter the

field of awareness (called open awareness or mindfulness medi-

tation); or a combination of both. There has been growing

interest in cancer care on the practice of a secular form of

mindfulness meditation called mindfulness-based stress reduc-

tion (MBSR), which is based on the work of Jon Kabat-

Zinn.
171

MBSR is typically delivered in an 8-week, struc-

tured group program consisting of a range of meditation

practices, including a sensate focus body scan, sitting medi-

tation, walking meditation, loving-kindness practice, and

gentle Hatha yoga postures. All formal practices are

designed to cultivate increasing levels of mindfulness in

day-to-day life. Participants engage in home practice daily

Integrative Therapies During and After Breast Cancer Treatment

202 CA: A Cancer Journal for Clinicians

throughout the program, and each session involves teaching

relevant concepts, discussions of progress and barriers to

practice, and introduction and practice of new meditation

modalities. Several recent articles and meta-analyses have

reviewed the literature on the use of MBSR in the oncology

setting, and some are specific to breast cancer.172-175

Mistletoe

The use of mistletoe in cancer care is based on the premise

that injections of specially prepared extracts of the plant

during chemotherapy and radiation therapy can create a

host response that is immune-stimulatory, preferentially

cytotoxic to cancer cells, and protective of host cells.
176

Mis-

tletoe is a parasitic plant from the Santalacea family that

attaches to and penetrates the branches of a tree or shrub to

absorb water and nutrients from the host plant. The use of

mistletoe as a medicine extends back centuries, whereas its

modern use for cancer care was promoted in Europe, and

particularly in Germany, in the early part of the 20th centu-

ry.
177

There are 3 main types of mistletoe: European mistle-

toe (Viscum album), Korean mistletoe (Viscum album var.

coloratum), and American mistletoe (Phoradendron leucar-

pum), but multiple methods of preparation and formulation

exist. Preparations from European mistletoe are some of the

most common internationally prescribed substances in out-

patient clinics for cancer, where they are delivered most

often as a subcutaneous injection or occasionally as an intra-

venous infusion.
178

While this therapy is often used clinical-

ly for its antineoplastic potential, clinical trial evidence on

the use of mistletoe is based on trials in which it is coadmi-

nistered with conventional treatments to improve QOL.
178

Music therapy

Music therapy is the clinical use of music to accomplish

individualized goals within a therapeutic relationship by a

credentialed professional.179 In cancer care, music therapy is

used to address various physical, emotional, cognitive, and

social needs. Qualified music therapists assess patients’

strengths and needs and provide indicated treatment, such

as creating, singing, moving to, and listening to music.

Music therapy interventions can be described as either pas-

sive (eg, listening to music before a medical intervention) or

active (eg, a therapist instructing a patient to engage in the

creation of live music), depending on the level of engage-

ment required. Although the exact mechanisms by which

music therapy works are not well understood, the most

commonly accepted theories are through neurologic, psy-

chological, behavioral, and physiologic pathways.180,181 The

practice of music therapy in North American is regulated by

some US states (Table 2).

Reflexology

In reflexology, a trained practitioner applies pressure to the

feet, hands, ears, and face using specific thumb, finger, and

hand techniques with the goal of stimulating the reflex areas

to promote physiologic changes in the body. The theory

behind reflexology states that specific areas on the feet and

hands correspond to specific glands, organs, and other parts

of the body, which are stimulated to help numerous health

problems.182 Reflexology is used to cause relaxation and

healing in those specific stimulated parts of the body. In

oncology, reflexology is often used to promote relaxation

and improve QOL.

Relaxation techniques

Various techniques are used to promote relaxation in

patients with cancer. The NCI defines relaxation techniques

as including progressive muscle relaxation (PMR), guided

imagery, autogenic training, biofeedback, self-hypnosis, and

deep breathing exercises.
183

PMR focuses on the tightening

and relaxation of specific, successive muscle groups and is

usually combined with breathing and imagery exercises.
183

Guided imagery can be self-directed or led by a practitioner

or a recording and often involves focusing on pleasant imag-

ery to replace negative or stressful feelings.
183

Autogenic

training involves concentrating on physical sensations of

warmth, heaviness, and relaxation in different parts of the

body.
183

Biofeedback uses electronic devices to monitor and

teach control of certain bodily functions, such as breathing

or heart rate, to facilitate relaxation.
183

Self-hypnosis refers

to training patients to induce a hypnotic state, which is a

natural state of aroused, attentive, focal concentration along

with a relative suspension of peripheral awareness, either on

their own or when prompted by a phrase or a cue.
183

Deep

breathing exercises involve the use of slow, deep, and even

breaths, sometimes called diaphragmatic or belly breathing.
183

Qigong

The word qigong consists of 2 Chinese words: qi (chee),

meaning life force or vital energy that flows through all

things in the universe, and gong (gung), meaning accom-

plishment or skill that is cultivated through steady prac-

tice.184 Qigong is a form of ancient and traditional Chinese

medicine that integrates movement (physical postures),

meditation (focused attention), and controlled breathing.

Qigong aims to enhance vital energy or life force that balan-

ces a patient’s spiritual, emotional, mental, and physical

health. Qigong practices are used to increase the qi, circulate

it, use it to cleanse and heal the body, store it, or emit qi to

help heal others. Practices range in intensity from the gentle

movements of tai chi to the more vigorous practice of kung

fu.184 In patients with cancer, qigong is often used to reduce

anxiety, fatigue, and pain; to support the immune system;

and to improve physical and emotional balance.

Stress management

Acute stress is a normal physical and emotional reaction

that people experience as they encounter changes in life,185

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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 203

including after a cancer diagnosis, during cancer treatment,

and throughout cancer survivorship. Long-term chronic stress

may contribute to or worsen a range of health problems,

including digestive disorders, headaches, sleep disorders,

depression, anxiety, and other mental health problems.185 To

address stress and induce the relaxation response, stress-

management programs teach techniques like PMR, guided

imagery, and breathing exercises. Stress management also

typically incorporates elements of cognitive-behavioral thera-

py, such as understanding the effects of appraisal and percep-

tion on the experience of subjective stress.186,187 Participants

are taught coping skills and practice various techniques for

cognitive reappraisal. One common structured group stress-

reduction program studied in oncology is called cognitive-

behavioral stress management.140,188 There are overlaps in

some techniques used in stress management, relaxation, and

meditation therapies. For example, meditation, guided imag-

ery, and yoga may be practiced as techniques in isolation or

combined. In this review, we distinguish between stress-

management, relaxation, and meditation interventions.

Stress-management interventions include psychoeducation on

stress and coping and emphasize cognitive-behavioral therapy

and coping skills training; relaxation interventions typically

consist of PMR and guided imagery; and meditation inter-

ventions use some form of meditation practice as the focal

point of the training.

Soy

Soy is a plant in the pea family that has been common in

Asian diets for thousands of year and more recently in the

American diet.
162

Soybeans are the seeds of the soy plant

and contain isoflavones and soy protein. Soy is available as a

dietary supplement in tablet or capsule form and contains

isoflavones and/or soy protein. Soybeans can be cooked or

eaten or may be used to make tofu, soy milk, and other food

products. Soy is also used as an additive to other processed

foods, such as baked goods. Soy is used to treat menopausal

symptoms, osteoporosis, memory problems, high blood

pressure, and high cholesterol levels.162 In patients with

cancer, soy is often used to treat hot flashes.

Yoga

Yoga is a mind-body practice with origins in ancient South

Asian philosophy and practice.
189

The term yoga is derived

from the Sanskrit word yug, meaning “yoke” or “union.”190

This, according to traditional yoga philosophy, is the ulti-

mate intent of a yoga practice—to unite the individual with

the totality of the universe. The techniques of yoga include

ethical daily living (yamas and niyamas), physical postures

(asanas), breathing techniques (pranayama), and meditation

training (dhyana). There is a wide range of yoga forms and

styles. The most commonly practiced form of yoga in the

United States and Canada is Hatha yoga, which emphasizes

postures (asanas) and often breathing exercises (pranayama).

In patients with cancer, yoga is used for a variety of condi-

tions, including stress, anxiety, depression, and fatigue, and

as a method to increase physical activity.

Literature Review on the Use of
Complementary and Integrative Therapies for
Clinical Outcomes in Patients With Breast
Cancer

The clinical outcomes addressed here are common symp-

toms and side effects experienced by patients with breast

cancer during treatment or as sequelae of treatment. The

outcomes of interest include: anxiety/stress, pain, depres-

sion/mood, fatigue, sleep disturbances, QOL and physical

functioning, CINV, radiation dermatitis, vasomotor out-

comes, lymphedema, CIPN, pain, and sleep disturbance.

Guidelines outlining conventional approaches to managing

these symptoms and outcomes have been issued by national

organizations like the National Comprehensive Cancer

Network and the American Society of Clinical Oncology,

but many of the prior guidelines and reviews did not include

thorough reviews of complementary and integrative medi-

cine approaches.191-197 This review fills that gap for patients

with breast cancer.

Below, for each therapy and clinical outcome of interest

that received a grade of A or B, we summarize the trials that

contributed to the graded recommendation to give the reader

an understanding of the specific interventions that were test-

ed. To provide additional context, there is a brief review of

the literature on the use of each integrative therapy for condi-

tions other than breast cancer. We also provide a risk/benefit

assessment of each therapy as well as suggestions for future

research. For therapies and clinical outcomes of interest that

received grades of C, D, or H, we provide a brief overview of

the rationale for the graded recommendation. The supporting

tables provide detailed information on each trial that informed

an A-graded or B-graded recommendation (see Supporting

Information Table 2,
26-48

Supporting Information Table

3,
26-30,33,35,40-43,45-48,53-56,59,60,69,72-90

Supporting Information

Table 4,27-29,43,46-48,73-75,82-85,104-106,127,128 and Supporting

Information Table 561-65). Table 3 lists the clinical outcomes

and integrative therapy combinations that had insufficient

evidence to make a grade A, B, C, D, or H recommen-

dation.26,33,36,37,40,43,45-50,52,69,72,73,76,77,79,83,84,87-89,94,97,104,108,111,

113,129,130,133-135,138,139,149,198-301

Updated Recommendations

Although the majority of graded recommendations remain

the same as those in the previously published guidelines,
9

there are 5 noteworthy changes. For the outcome of anxiety

and stress reduction, the use of meditation moved from

grade B to grade A because of results from a fifth trial,26 in

Integrative Therapies During and After Breast Cancer Treatment

204 CA: A Cancer Journal for Clinicians

addition to the previously published 4 trials,27-30 showing

beneficial effects. The use of yoga for depression and mood

disturbance was downgraded from grade A to grade B

because of 4 new published studies demonstrating conflict-

ing results.
40,79-81

The use of yoga for improving QOL

changed from grade C to grade B, because 2 additional trials

demonstrated beneficial effects.
104,128

Finally, new trials

on the use of yoga40,80,104 and hypnosis97,98 for fatigue

upgraded previous recommendations from grade I to grade C.

Use of Integrative Therapies for Anxiety/Stress
Reduction

Description of anxiety/stress

Patients with cancer may experience stress related to the life

changes associated with a cancer diagnosis, both during and

after treatment. Under the NCI’s Common Terminology

Criteria for Adverse Event (CTCAE) psychiatric disorders,

anxiety is categorized from grade 1 (mild symptoms and no

intervention required) to grade 4 (life-threatening). Stress is

often the result of life challenges that exceed the individual’s

perceived ability to cope and is a common and normal reac-

tion during cancer diagnosis and treatment. This stress is

associated with symptoms of anxiety and somatic complaints

that can significantly diminish QOL.302 Patients with anxi-

ety may worry more frequently, have difficulty relaxing, or

feel tense. Patients with cancer-related anxiety also may

have elevated heart rate, myalgias, headaches, sleep distur-

bances, changes in appetite, nausea, diarrhea, and difficulty

concentrating. The percentage of patients with breast cancer

who report anxiety ranges from 12% to 47%, and approxi-

mately 11% to 16% of patients experience combined symp-

toms of anxiety and depression.303-305 Evidence suggests

that effective anxiety management is associated with

improvements in QOL, psychological adjustment, under-

standing of the disease, decision making, and adherence to

treatment.306-308

Meditation (A grade)

Overview of meditation interventions for anxiety/stress

reduction. Meditation is recommended for reducing anxiety

in patients with breast cancer, including during radiation

therapy (grade A). Many uncontrolled trials have been pub-

lished, but this recommendation is based on 5 RCTs com-

pleted between 2009 and 2013 that used meditation to

reduce anxiety symptoms (see Supporting Information

Table 2).26-30 Anxiety was the primary outcome for 4 of

those trials. In all 5 studies, a meditation intervention was

compared with a usual-care control condition. Study partici-

pants included women undergoing radiation or chemothera-

py, breast cancer survivors who had completed treatment,

and older adult breast cancer survivors ages 50 years and

older. The study sample sizes ranged from 49 to 336 partici-

pants. Among these trials, 3 types of meditation

interventions were tested. Three trials implemented an

intensive, integrated MBSR program customized for

patients with breast cancer in which participants were

trained in mindfulness meditation and gentle yoga for body

awareness.
26,29,30

A fourth intervention was called the

Mindful Movement Program and was also an intensive,

integrated program customized for patients with breast can-

cer that included mindful walking/moving, group discus-

sion, exploration of body parts, specific and deliberate

movements, moving with intentional effort, active energetic

movement, and partner work.27 The fifth trial assessed a

brain wave vibration meditation28 or a mind/body training

technique that combined simple, rhythmic movements with

music, action, and positive messages.
26

A systematic review and meta-analysis examined medita-

tion in terms of its ability to reduce general psychological

distress and stress-related health problems in adult clinical

populations with a variety of health conditions; that analysis

included 47 trials with 3515 participants.309 Overall, mind-

fulness meditation programs demonstrated moderate evi-

dence of improved anxiety at 8 weeks and at 3 to 6 months

and showed low evidence of improved stress/distress and

mental health-related QOL. The findings of these reviews

across other patient populations and disease types support

our recommendations.

The earliest work in MBSR interventions specifically

demonstrated sustained benefits for individuals with anxiety

disorders, and more recent research has continued to show a

benefit for generalized anxiety.
310-312

The first study con-

ducted in patients with cancer, an RCT of 89 patients with

a variety of cancer types, found substantial decreases in anxi-

ety for the group that received MBSR compared with

results for a usual-care control group; results for the MBSR

interventions were maintained at 6-month follow-up.313,314

The reduction in anxiety observed in the above-described

trials, specifically those that used more traditional forms of

MBSR, provide support for the recommendation that medi-

tation can be beneficial for the management of anxiety in

women with breast cancer.

A recent systematic review and meta-analysis of 22 stud-

ies examined the effect of mindfulness-based therapy specif-

ically on symptoms of anxiety and depression in adult

patients with cancer and cancer survivors; of those 22 stud-

ies, 21 included either a substantial percentage of patients

with breast cancer or only patients with breast cancer.315

Overall, that review included 12 nonrandomized studies and

RCTs. In the nonrandomized studies, mindfulness-based

therapy was associated with significantly reduced symptoms

of anxiety postintervention with a moderate effect size,

while the pooled effects sizes of RCTs, including that dis-

cussed above,
29

resulted in a larger effect size (P < .001).

Although the review reported that overall study quality

CA CANCER J CLIN 2017;67:194–232

VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 205

varied among the studies included, there appears to be sound

evidence from carefully conducted RCTs (n 5 9) supporting

the use of mindfulness-based therapies for the management of

anxiety in patients with breast cancer and in breast cancer sur-

vivors. Another review of 9 studies (including 2 RCTs, a

quasi-experimental case-control study, and 6 single-group pre/

post-intervention studies) investigated the efficacy of MBSR

on mental health specifically in patients with breast cancer and

found an overall decrease in anxiety scores after MBSR (P <

.01).
174

That review provides further support for the use of

MBSR to manage anxiety, specifically in women with breast

cancer. Many other reviews reached similar conclusions,

reporting positive, moderate effect sizes of mind-body inter-

ventions (MBIs) on anxiety and distress in cancer.174,175,316

TABLE 3. Clinical Outcomes and Integrative Therapies With Insufficient Evidence to Form a Clinical Recommendation
(I-Statement)

a

OUTCOME INTEGRATIVE THERAPIES

Adherence Acupressure,198 multimodal199

Anemia LCS101 combination botanical,200 RG-CMH combination botanical,201 shenqi fuzheng injection202

Anxiety/stress reduction Art therapy,203,204 comprehensive coping strategy,205 electrical nerve stimulation,206 healing touch,94,207

hypnosis,208 myofascial release,209 multimodal,210,211 reflexology,138,139,212 reiki,213 tai chi214

Cardiomyopathy N-acetylcysteine215

Chemotherapy-induced
nausea and vomiting

Acupressure,216 aromatherapy,217 Agaricus sylvaticus,218 Cocculine (complex homeopathic Rx),219

comprehensive coping strategy,205 massage,52 Nevasic audio program,220 yoga43

Cognition Natural environment,221 Ginkgo biloba,222 meditation,72 yoga223

Constipation Self-management program224

Depression/mood Art therapy,203 Biofield Healing,225 comprehensive coping strategy,205 CoQ10,226 electrical nerve
stimulation,206 Gandoderma lucidium,227 guarana,108 hypnosis,228 multimodal,199,210,229,230 myofascial
release,209 qigong,135 reflexology,138,139 tai chi214

Fatigue Acupressure,198 acupuncture,50,231,232 Biofield Healing,225 comprehensive coping strategy,205 CoQ10,226

Gandoderma lucidium,227 light treatment,233 massage,87 meditation,72,76 mind-body cognitive therapy,234

movement,235 multimodal,230,236,237 multivitamin,238 polarity therapy,239,240 stress management,241 qigong,135

reflexology,139 relaxation,242,243 stress management,36 yoga40,46-48,79,83

Lymphedema CYCLO 3 FORT,244 electrotherapy,245 ginkgo forte,246 pentoxifyline and vitamin E,247,248 yoga249

Neuropathy Omega 3 fatty acids,250 vitamin E,251,252 acupuncture130

Neutropenia/leukopenia Cat’s claw,253 LCS101 combination botanical,200 RG-CMH combination botanical,201 mistletoe,133,134 shenqi
fuzheng injection202

Pain Comprehensive coping strategy,205 stress management,36 vitamin D2,254 electrical nerve stimulation,206 cognitive
and behavioral therapy,255 hypnosis,256 massage,88 myofascial release,209 reflexology139,212

Quality of life Acupressure,216 Biofield Healing225 calendula cream,257 cannabis,258 chlorella extract,259 CoQ10,226

curcuminoids,260 electrical nerve stimulation,206 electrotherapy,245 flaxseed,261 Ganoderma lucidum,227

gingko forte,246 guided imagery,262 healing touch,94 homeopathy,263-265 hypnosis,97 laser therapy,111 manual
lymphatic draining,113 massage,87 meditation,26,72 movement,235,264 music therapy,89

multimodal,199,210,230,236,237,267 multivitamin,238 polarity therapy,239,240 relaxation,69,77 shenqi fuzheng,202 shark
cartilage,268 soy,149 supportive-expressive group therapy,269 tai chi214,270-272

Physical functioning Mind-body cognitive therapy,234 music therapy,33 multimodal,199 myofascial release,209 reflexology,139 stress
management,37 tai chi,270,272 yoga45,79,84,273

Radiation therapy-induced
toxicity outcomes

Adlay bran extract,274 alpha ointment with henna,275 Aquaphor-Biafine-Radiacare,276b boswellia cream,277

calendula cream,257,278 chamomile,279 curcumin,280 glutamine,281 homeopathic pills,282 honey,283,284

hydration,285 massage,286 oil-in-water emulsion,287, glutathione and anthocyanin gel,288c wheat grass extract,289

pentoxifylline and vitamin E290,291

Sleep disturbance Acupuncture,49,50,129 calendula cream,257 meditation,72,292-294 qigong,135 stress-management techniques36

Vasomotor outcomes Black cohosh,295,296 flaxseed,261 homeopathy,264,265 hypnosis,297 magnetic therapy,298 meditation,73

peppermint,299 vitamin E,300 yoga104,301

Abbreviations: CoQ10, coenzyme 10Q; CYCLO 3 FORT, fluid extract of Ruscus aculeatus, hesperidin methyl chalcone, and vitamin C; LCS101, a botanical com-
pound mixture; RG-CMH, a Chinese medicinal herb complex.

a
Definition of the I Statement: Concludes that the current evidence is insufficient to assess the bal-

ance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read
the Clinical Considerations section of the US Preventive Services Task Force Recommendation Statement. If the service is offered, then patients should under-
stand the uncertainty about the balance of benefits and harms.

b
Suppliers for these topicals are as follows: Aquaphor (Beiersdorf AG, Hamburg, Germany), Biafine

(Laboratoire Medix, Houdan, France), and RadiaCare (Medline Industries, Inc., Northfield, IL).
c
RayGel is a proprietary glutathione and anthocyanin gel.

Integrative Therapies During and After Breast Cancer Treatment

206 CA: A Cancer Journal for Clinicians

Risk/benefit assessment of meditation interventions.

Meditation therapies pose very little risk to participants in

this type of intervention. Few adverse events have been

reported in any trials, but there has been recent interest

within the meditation research community in exploring

adverse reactions to intensive meditation practice, particu-

larly in vulnerable individuals.317,318 Typically, potential

participants are screened through individual orientation

interviews before joining meditation group programs, and

participants who have serious mental health issues are often

redirected to individual counseling or psychiatric interven-

tion before or concomitant with MBI participation. Group

facilitators are typically mental health care professionals

trained to identify and manage psychological symptoms and

reactions that may occur during the training.

Participants in these meditation therapy groups typically

report that the sessions are enjoyable, and dropout rates are

often low and are comparable to the rates in other psychoso-

cial group programs. Because they are offered in group set-

tings, meditation interventions are more cost effective than

traditional individual counseling or psychotherapy and can

often achieve similar results. However, the literature on

meditation therapy is lacking in head-to-head comparisons

with other forms of therapy, including individual counsel-

ing, cognitive-behavioral therapy, or other MBIs. Hence,

the specificity of meditation therapy is not yet known. With

the exception of the trial reported by Carlson et al,
26

studies

have not compared MBIs with other effective interventions.

Other research suggests that the benefit is related to the

degree of the participant’s engagement in and commitment

to the practice,313,319 in that participants who practice more

at home often benefit more, but this area is still being inves-

tigated.
320

Drawbacks of these types of group interventions

are the requirement for highly trained facilitators and the

need for and ability of participants to attend in person, usu-

ally in large cities with tertiary cancer centers. In response to

these issues, online and home-based adaptations of MBIs

are being developed. For example, Zernicke et al
321

demon-

strated that an online, live MBI group in which rural

and remotely located patients who had cancer participated

weekly over 8 weeks had similar benefit to the on-site, in-

person version; and patients were highly satisfied with the

remote MBI adaptations.

Future research in meditation interventions for anxiety

reduction. Future research on the use of meditation inter-

ventions for anxiety can similarly test novel interventions in

populations that may not have ready access to in-person

meditation programs.

Music therapy (B grade)

Overview of music therapy interventions for anxiety/

stress reduction. Passive music therapy is recommended to

reduce anxiety during radiation therapy, chemotherapy ses-

sions, and postsurgery (grade B) based on results from

5 RCTs comparing music therapy interventions with stan-

dard care (see Supporting Information Table 2).31-35 Study

participants included patients with breast cancer who were

undergoing mastectomy, chemotherapy, and/or radiation

therapy. The sample sizes of these studies ranged from 30 to

170 participants. The music therapy interventions were

described as either passive or active music therapy, depend-

ing on the level of engagement required by the individual.

Four trials examined the effect of passive music therapy,

which was found to decrease anxiety scores in the interven-

tion group,31,32,34,35 including reducing sedation require-

ments during radiation therapy (measured as a secondary

outcome).
31,32,34

The fifth trial, which was conducted by

Hanser et al,33 examined active music therapy (which

required active engagement of the participant) and yielded

substantially different results from the 4 trials of passive

music therapy. In that study, active music therapy did not

result in decreases in anxiety. The discrepancy in trial results

between passive and active music therapy might have

occurred because the participant engagement required for

active therapy does not include the potential relaxing com-

ponents of passive music therapy (eg, listening to music).

A recent systematic review and meta-analysis by Boehm

et al
322

assessed the effect of different expressive therapies,

including passive and active music therapy, on improving

anxiety, depression, and QOL in patients with breast can-

cer. The review included 3 of the RCTs that formed the

basis for our recommendation of passive music therapy for

anxiety/stress reduction, of which 2 trials tested passive

music therapy,31,34 and the other tested active music thera-

py.33 Another recent meta-analysis included an additional

RCT evaluating art therapy.
204

Boehm et al found a clini-

cally and statistically significant mean difference (P < .01)

in the anxiety scores of patients who received music therapy

compared with the control group,322 thus further supporting

our recommendation of passive music therapy for reducing

anxiety. Passive music therapy has also been shown to

reduce anxiety among patients undergoing mammographic

screening, indicating that the recommendation may apply

broadly to adult women in a clinical cancer setting.323

Risk/benefit assessment of music therapy. Passive music

therapy is noninvasive, does not interfere with a patient’s

privacy, and has no reported deleterious effects. Further-

more, it does not require costly, technologically advanced

equipment and can be implemented in a variety of locations.

As such, passive music therapy can be safely and effectively

implemented in clinical settings for patients with breast can-

cer to help reduce short-term anxiety associated with receiv-

ing medical care for their cancer.

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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 207

Future research in music therapy for anxiety reduction.

Future research should assess the long-term effects of pas-

sive music therapy on anxiety, because the trials reviewed

here only assessed short-term reductions in anxiety.

Although active music therapy may also have benefit, more

than one existing trial will be needed for a comprehensive

risk/benefit assessment. Trials that directly compare the

effect of passive versus active music therapy on anxiety are

needed to clarify whether the benefit is because of listening

to music in a relaxed state or participating in the creation of

music.

Stress management (B grade)

Overview of stress-management interventions for anxi-

ety/stress reduction. Stress management is recommended

to reduce anxiety in patients during breast cancer treatment

(grade B), but long-term stress-management group pro-

grams appear to be better than self-administered home pro-

grams. This recommendation is based on 4 RCTs, which

were completed between 2008 and 2013 among patients

with breast cancer, testing a stress-management intervention

compared with usual care using an improvement in anxiety

as the primary outcome.36-39 Study participants included

only patients who had breast cancer in 2 of the 4 trials
36,39

and a mixed group of patients with cancer that included a

significant proportion of women who had breast cancer in

the other 2 trials.
37,38

In all 4 trials, patients with breast can-

cer were included from defined periods along the continuum

of care, including before surgery, during chemotherapy, and

after cancer treatment. Patients thus were either undergoing

or had undergone surgery, chemotherapy, or radiation ther-

apy, either alone or in combination. The study sample sizes

for these trials ranged from 85 to 286 participants. Of the 4

trials, 2 indicated that the improvement was statistically sig-

nificantly different compared with the control group.
37,39

One trial found a similar improvement in both the interven-

tion and control groups with no statistically significant dif-

ferences across groups,36 and the fourth trial found no

improvement38 (see Supporting Information Table 2, Stress

Management).

Stress-management interventions varied among the stud-

ies (see Supporting Information Table 2).
36-39

One trial
38

implemented a self-administered stress-management inter-

vention before patients received chemotherapy. The inter-

vention included video and booklet information specific to

stress management and exercise and was delivered by a

doctoral-level psychologist.
38

A second trial
36

offered stress-

management modalities that included guided imagery tech-

niques, relaxation, meditative exercises, and counseling that

aimed to promote active coping, alert relaxation, and a posi-

tive attitude toward change. Instruction was given in person

and was complemented by audio CDs for use at home.

Face-to-face sessions lasted from 45 to 60 minutes each and

took place in the hospital.36 The stress-management portion

included information, demonstrations and instructions for

paced breathing, PMR with guided imagery, and the use of

coping strategies to manage stress. A third trial,37 which

took place at a multicenter community clinical oncology

program involving 20 clinical sites, was designed to deter-

mine whether a self-administered stress-management inter-

vention that was previously identified as beneficial for

patients with cancer would improve QOL and decrease psy-

chological distress (including anxiety and depression) in

patients receiving chemotherapy at community clinical cen-

ters. The study used a factorial design to test stress-

management training, exercise training, combined stress-

management and exercise training, and usual care. Patients

assigned to stress-management training were provided writ-

ten materials and videos on 3 techniques, including PMR

and guided imagery, abdominal breathing, and coping skills

training.37 A fourth trial39 examined the effects of a

cognitive-behavioral stress-management intervention (com-

prised of relaxation training, including meditation, guided

imagery, PMR and breathing techniques, cognitive restruc-

turing, and coping skills training) on late-afternoon serum

cortisol and relaxation indicators in women undergoing

treatment for nonmetastatic breast cancer.

A systematic review by Trijsburg et al evaluated the

effects of stress-management techniques on mental health

outcomes, including anxiety, across 22 studies using samples

from heterogeneous cancer populations that included 6

studies of breast cancer-only samples.
324

The interventions

assessed were all structured and included counseling and

coping components in addition to some interventions,

including PMR, guided imagery, self-hypnosis, and deep

breathing. Overall, the review found positive effects for

mental health outcomes, including anxiety scores.

Risk/benefit assessment of stress-management interven-

tions. Stress-management therapy is noninvasive, nontoxic,

and has no appreciable risk to patients. Stress management

does not require specialized equipment and can be imple-

mented in a variety of locations. Resources for providing

instruction on self-management practices are broadly avail-

able. Because the majority of trials discussed above tested

long-term interventions, the guideline recommendation is

specific to long-term stress-management programs. Howev-

er, this may be complicated by other factors, including a

potential increase in the cost of delivery for providers/facili-

tators as a result of the implementation of longer term pro-

grams, and it also could present a barrier to patients who

have access-to-care and other health care disparity issues.

Overall, it is recommended that stress-management therapy

can be safely and effectively implemented in clinical settings

for patients with breast cancer.

Integrative Therapies During and After Breast Cancer Treatment

208 CA: A Cancer Journal for Clinicians

Future research in stress-management interventions for

anxiety reduction. Future research in this area should com-

pare in-person, professionally led stress-management group

programs versus home-based, self-study, and internet-based

stress-management intervention options, which are less

costly and more broadly accessible. Research should also

examine long-term outcomes for each type of delivery

modality.

Yoga (B grade)

Overview of yoga interventions for anxiety/stress reduc-

tion. Yoga is recommended for reducing anxiety in

patients with breast cancer (grade B). This recommenda-

tion is based on 9 RCTs, completed between 2007 and

2014, in which a yoga intervention was implemented to

reduce physical symptoms and psychological distress,

including anxiety, which was assessed as the primary out-

come in 4 of the studies (see Supporting Information

Table 2).
40-48

Those 9 trials tested 5 different yoga inter-

ventions. The first intervention was an intensive, integrat-

ed yoga program customized for patients with breast

cancer, in which participants were led through slow

stretching and loosening exercises, various postures (asa-

nas), guided imagery specific to cancer, positive thought

provocation, chanting exercises, various breathing exer-

cises (pranayama), and soothing sound vibrations and

guided imagery (yoga nidra).
41-44

A second intervention

implemented Iyengar yoga, a traditional form of Hatha

yoga emphasizing postures and breathing techniques that

target symptom-specific concerns using passive inversions

(upside-down postures with the head lower than the heart)

and passive backbends (supported spinal extensions).
45

A

third intervention used Patanjali’s yoga sutras, which

included warm-up movements synchronized with breath-

ing, selected postures, deep relaxation techniques,

alternate-nostril breathing (pranayama), and meditation.48

The fourth intervention implemented meditation and

breathing exercises that focused attention on internal body

sensations as well as yoga exercises (modified asanas) com-

posed of gentle stretching and strengthening exercises.
40

Pranayama or yoga breathing practices were tested in the

remaining trials.
46,47

Study participants included women

who had been recently diagnosed with breast cancer, those

who were currently receiving radiation or chemotherapy or

a combination of both, and those who were experiencing

significant fatigue post-treatment. The study sample sizes

ranged from 23 to 98 participants.

Several recent reviews of yoga interventions for individu-

als with cancer have been published.325-328 The first meta-

analysis investigating the impact of yoga interventions on

psychological health outcomes329 identified 10 articles that

examined outcomes in patients with breast cancer (n 5 7

articles), patients with lymphoma (n 5 1), and mixed cancer

populations (n 5 2). Analyses involving 8 trials that assessed

anxiety found that lower anxiety was associated with the

yoga groups relative to controls (P 5 .009); and similar

results with yoga interventions were observed for distress

(P 5 .003) and stress (P 5 .006). However, because this

was a heterogeneous sample of patients, it was unclear

whether the results could be generalized specifically to

patients with breast cancer. More recently, a systematic

review and meta-analysis assessing the impact of yoga inter-

ventions on QOL and psychological health specifically in

patients with breast cancer and survivors was conducted.
330

Overall, 12 RCTs were included in the analysis with a total

of 742 participants. Analyses revealed short-term positive

effects of yoga interventions on improved psychological

health, including anxiety (P < .01), perceived stress (P 5

.03), and psychological distress (P < .01). However, it is

notable that these effects were applicable only to those who

engaged in yoga during active cancer treatment and not in

the post-treatment period. The authors stated that, based

on these positive preliminary results, a wide variety of yoga

practices could be recommended for this population.330

Finally, although the methodological quality across the trials

varied, it has been demonstrated that yoga is beneficial for

reducing psychological distress in a wide variety of non-

cancer clinical populations, including adult patients with

anxiety and depression.331,332

Risk/benefit assessment of yoga interventions. Yoga

interventions are noninvasive and, with proper instruction,

can be adapted to people who have functional and other

impairments without harm. Yoga interventions are low cost

and can be practiced at home with instructional videos;

however, in the context of breast cancer, they are best

undertaken under the guidance of certified yoga instructors

who have specific training in teaching patients with cancer

and cancer survivors. Such programs also have the ability to

be adapted and modified for people with medical conditions

or limited mobility.333 Older adults, individuals with limited

mobility, and those with chronic medical conditions should

proceed with yoga therapy only under the guidance of a cer-

tified instructor to minimize the potential risk of harms

such as strained muscles and dizziness if yoga postures are

attempted incorrectly or prematurely.

Future research in yoga interventions for anxiety reduc-

tion. Many of the studies investigating the impact of yoga

on psychological outcomes in individuals with cancer

should be interpreted with caution, because many of these

studies are small and preliminary. Furthermore, the studies

summarized above have some inconsistency of results; the

trials from India41-44 reported consistently positive results,

while the trials from North America40,45-48 reported less

consistent positive results. Nevertheless, many of the

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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 209

studies and reviews that examined yoga interventions

reported overall positive outcomes in several physical, psy-

chological, and QOL measures. Future trials of yoga inter-

ventions for anxiety/stress reduction should focus on

testing forms of yoga that can be more easily applied and,

to improve the generalizability of the results, should test

the interventions in larger sample size and in minority and

underserved populations that may not have easy access to

yoga programs.

C-graded therapies for anxiety and stress reduction

Acupuncture,49-51 massage,52-55 and relaxation56-60 can be

considered for reducing anxiety and stress (grade C). Three

high-quality trials assessed acupuncture for anxiety and

stress reduction, which were secondary outcomes; 2 of the 3

positive trials were small,
49,50

and the other demonstrated

no effect.51 However, of 4 studies that examined massage

for anxiety, 3 with positive findings included fewer than 40

participants,52-54 and the other demonstrated no effect.55

Results were inconclusive regarding relaxation for anxiety

and stress reduction because of inconsistencies and small

sample sizes. Future directions in research can focus on eval-

uating these modalities in a large, high-quality trial assess-

ing anxiety as the primary outcome.

Use of Integrative Therapies for Depression/Mood
Disturbances

Description of depression/mood disturbances

Both during and after cancer therapy, patients may experi-

ence symptoms of depression, as they often feel a sense of

loss of health and the life they had before their cancer diag-

nosis.302 The CTCAE categorizes depression as a psychiat-

ric disorder on a scale from 1 (mild) to 5 (death). Symptoms

of depression in patients with cancer may include persistent

feelings of sadness, numbness, nervousness, guilt, worthless-

ness, helplessness or hopelessness, difficulty concentrating

or behavior that includes being short-tempered or moody,

crying for long periods of time or many times each day,

lacking interest or pleasure in performing activities, and

having suicidal thoughts. Other symptoms may include

weight change, sleep disturbances, tachycardia, dry mouth,

increased perspiration, gastrointestinal symptoms, diarrhea,

changes in energy level, persistent fatigue, headaches, or

myalgias. The percentage of patients with breast cancer

reporting depression ranges from 3% to 34%, and 11% to

16% of patients experience combined depression and anxiety

symptoms, depending on the population studied.303-305

Effectively managing depression may improve QOL, psy-

chological adjustment, understanding of the disease, deci-

sion making, adherence with cancer treatment, and response

to cancer treatment.
306-308

Meditation (A grade)

Overview of meditation interventions for depression/

mood disturbances. Meditation, particularly MBSR, is

recommended for treating mood disturbance and depressive

symptoms in patients with breast cancer (grade A). This

recommendation is based on 10 RCTs, completed between

2009 and 2015, that used meditation to help reduce depres-

sive symptoms (see Supporting Information Table

3).26-30,72-76 Depression was the primary or secondary out-

come for all of these trials. In 8 of the 10 trials,27-30,72-74,76

a meditation intervention was compared with a usual care

group, a waitlist control group, or another active interven-

tion; 2 other trials used a 3-arm trial design.26,75 Study par-

ticipants included women undergoing current radiation

therapy or chemotherapy for breast cancer, breast cancer

survivors who had completed treatment, and adult breast

cancer survivors ages 55 years and older. The study sample

sizes ranged from 33 to 336 participants and tested 6 differ-

ent types of meditation interventions, including an inten-

sive, integrated MBSR program customized for patients

with breast cancer26,29,30,73,75; the Mindful Movement Pro-

gram73; brain wave vibration meditation28; Tibetan sound

meditation72; cognitively based compassion training76; and

Transcendental Meditation.74

In the meta-analysis examining the effect of mindfulness-

based therapy on psychological outcomes in adult cancer

populations,
315

compared with results in controls,

mindfulness-based therapy was associated with significantly

reduced depression postintervention, with a moderate effect

size in the nonrandomized studies and RCTs, including one

trial listed above29 (P < .001). By using evidence from 9

well conducted studies, the review and meta-analysis by

Zainal et al confirmed the use of mindfulness-based thera-

pies for the management of depression in patients with

breast cancer and survivors despite the heterogeneity in the

reviewed studies; the results of the meta-analysis identified a

significant pooled effect size for MBSR on depression scores

(effect size, 0.575; 95% confidence interval, 0.429-0.722

[P < .01]).174 In their study, Teasdale et al334 modified

traditional MBSR by combining it with principles of cogni-

tive behavioral therapy to create mindfulness-based cogni-

tive therapy, which was designed specifically to prevent

recurrence of depressive symptoms in individuals with

relapsed major depression.335 The intervention proved

effective for preventing depression relapse334 and has since

been widely applied and adapted to treat depression symp-

toms in a range of clinical samples.336 In patients with can-

cer, other RCTs of meditative interventions resulted in

decreased depressive symptoms,313 with results maintained

after 6 months of follow-up.314 The reduction in depressive

symptoms observed in the above-described trials comprising

these reviews and meta-analyses provide further support for

Integrative Therapies During and After Breast Cancer Treatment

210 CA: A Cancer Journal for Clinicians