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ARTICLE TITLE: Clinical Practice Guidelines on the Evidence-Based Use of Integrative Therapies During and After Breast Cancer Treatment
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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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hi ne
se he
rb o lo
gy ,
an d
O ri
en ta
l m
ed ic
in e
ar e
re gu
la te
d vi
a st
at e
lic en
si ng
bo di
es .
Th e
N at
io na
l C
er ti
fi ca
ti o n
C o m
m is
si o n
fo r
A cu
pu nc
tu re
an d
O ri
en ta
l M
ed ic
in e
(N C
C A
O M
) re
po rt
s th
at 4
4 st
at es
pl us
th e
D is
tr ic
t o f
C o lu
m bi
a ha
ve ac
up un
ct ur
e pr
ac ti
ce ac
ts .
Fo rt
y- th
re e
st at
es cu
rr en
tl y
re qu
ir e
pa ss
ag e
o f
N C
C A
O M
na ti
o na
l ex
am in
at io
ns fo
r in
it ia
l lic
en su
re .
Th e
N C
C A
O M
ce rt
if ie
s ac
up un
ct ur
e, C
hi ne
se he
rb o lo
gy ,
an d
O ri
en ta
l m
ed ic
in e.
C ur
re nt
ly ,
C al
if o rn
ia re
qu ir
es pa
ss ag
e o f
it s
o w
n st
at e
ex am
in at
io ns
fo r
lic en
su re
an d
do es
no t
ac ce
pt th
e N
C C
A O
M ce
rt if ic
at io
n. A
su bs
et o f
st at
es re
gu la
te s
ac up
re ss
ur e
un de
r ac
up un
ct ur
e o r
m as
sa ge
re gu
la ti
o ns
.
C A
N A
D A
: A
cu pu
nc tu
re is
re gu
la te
d vi
a pr
o vi
nc ia
l lic
en si
ng bo
di es
in th
e pr
o vi
nc es
o f
B ri
ti sh
C o lu
m bi
a, A
lb er
ta ,
O nt
ar io
, Q
ue be
c, an
d N
ew fo
un dl
an d.
C hi
ne se
m ed
ic in
e is
cu rr
en t-
ly o nl
y re
gu la
te d
in B
ri ti
sh C
o lu
m bi
a an
d O
nt ar
io .
A C
A O
M ,
ac ao
m .o
rg ;
N C
C A
O M
, m
x. nc
ca o m
.o rg
C ol
le ge
of Tr
ad iti
on al
C hi
ne se
M ed
ic in
e Pr
ac tit
io ne
rs an
d A
cu -
pu nc
tu ris
ts of
B rit
is h
C ol
um bi
a (C
TC M
A ),
ct cm
a. bc
.c a;
C ol
le ge
of Tr
ad it io
na l
C hi
ne se
M ed
ic in
e Pr
ac tit
io ne
rs an
d A
cu pu
nc tu
ri st
s of
O nt
ar io
(C TC
M PA
O ),
ct cm
pa o.
on .c
a/ ;
C ol
le ge
an d
A ss
oc ia
ti on
of A
cu pu
nc tu
ris ts
of A
lb er
ta (C
A A
A ),
ac up
un ct
ur ea
lb er
ta .c
a/ ;
A ss
oc ia
tio n
of A
cu pu
nc tu
ris ts
of Q
ue be
c (A
A Q
), ac
up un
ct ur
e- qu
eb ec
. co
m /e
n/ ho
m e.
ht m
l; N
ew fo
un dl
an d
an d
La br
ad or
C ou
nc il
of H
ea lth
Pr of
es si
on al
s (N
LC H
P) ,
nl ch
p. ca
/
H yp
no si
s M
en ta
l he
al th
an d
m ed
ic al
pr o fe
ss io
na ls
ty pi
ca lly
pr ac
ti ce
hy pn
o si
s as
a sp
ec ia
lt y
o r
su bs
pe ci
al ty
. C
er ti
fi ed
hy pn
o -
th er
ap is
ts ,
in ge
ne ra
l, ho
ld a
gr ad
ua te
-l ev
el o r
ba ch
el o r’
s- le
ve l
de gr
ee in
a br
o ad
ra ng
e o f
sp ec
ia lt
ie s,
in cl
ud in
g M
D ,
re gi
st er
ed nu
rs e,
de nt
is t,
so ci
al w
o rk
er ,
lic en
se d
co un
se lo
r o r
ps yc
ho lo
gi st
. pa
st o ra
l co
un se
lo r,
o rd
ai ne
d m
in is
te r,
an d
ch ir
o pr
ac to
r, am
o ng
m an
y o th
er s,
pr io
r to
o bt
ai ni
ng tr
ai ni
ng in
hy pn
o si
s.
C ur
re nt
ly ,
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
A ss
o ci
at io
n fo
r M
us ic
Th er
ap y
(C A
M T)
, m
us ic
th er
ap y.
ca /
R el
ax at
io n
an d
st re
ss m
an ag
em en
t R
el ax
at io
n an
d st
re ss
m an
ag em
en t
ar e
us ua
lly pr
o vi
de d
by tr
ai ne
d m
en ta
l he
al th
pr o fe
ss io
na ls
, su
ch as
re gi
st er
ed /c
ha rt
er ed
/ co
un se
lin g
ps yc
ho lo
gi st
s, ps
yc hi
at ri
st s,
m ar
it al
an d
fa m
ily co
un se
lo rs
, cl
in ic
al so
ci al
w o rk
er s,
an d
nu rs
es .
A ny
o f
th es
e pr
o fe
ss io
ns co
ul d
ha ve
sp ec
if ic
tr ai
ni ng
in th
es e
2 m
o da
lit ie
s.
Ty pi
ca lly
, th
e af
o re
m en
ti o ne
d pr
o fe
ss io
na ls
w o ul
d ta
ke co
ur se
s in
re la
xa ti
o n
tr ai
ni ng
o r
st re
ss m
an ag
em en
t as
pa rt
o f
th ei
r tr
ai ni
ng .
Ev er
y ju
ri sd
ic ti
o n
ha s
a co
lle ge
o f
ps yc
ho lo
gi st
s an
d so
ci al
w o rk
er s.
A m
er ic
an Ps
yc ho
lo gi
ca l
A ss
o ci
at io
n (A
PA ),
ap a.
o rg
/; C
an ad
ia n
Ps yc
ho lo
gi ca
l A
ss o ci
at io
n (C
PA ),
cp a.
ca
Y o ga
Th er
e ar
e ve
ry st
ri ng
en t
cr it
er ia
to be
a yo
ga in
st ru
ct o r,
an d
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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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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 201
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
the recommendation that meditation can be beneficial for
the management of depressive symptoms in women with
breast cancer.
Risk/benefit assessment of meditation interventions.
The risk/benefit assessment of the effects of meditation
intervention on depression and mood disturbance outcomes
is similar to the assessment of anxiety outcomes. Despite
these limitations, the evidence suggests that meditation and
MBSR could be added to treatment plans or in the post-
treatment period, provided that these interventions are facil-
itated by appropriately trained instructors and can be
adapted and modified if needed for individuals with cancer.
Future research in meditation interventions for depres-
sion/mood. Future research on meditation interventions to
improve mood disturbances/depression should focus on
understanding the type, duration, and lasting effects of spe-
cific meditation techniques on specific mental health
outcomes.
Relaxation (A grade)
Overview of relaxation interventions for depression/
mood disturbances. Relaxation therapy is recommended
for improving mood disturbances and depressive symptoms
when added to standard care (grade A). The recommenda-
tion put forth in the guidelines is based on results from 6
RCTs, completed between 1999 and 2007, which imple-
mented a relaxation program with or without guided imag-
ery as an intervention to improve mood disturbances and
treat depression (see Supporting Information Table
3).56,59,60,69,77,78 Five of the 6 trials measured depression as
the primary outcome. In all 6 trials, a relaxation therapy
intervention group was compared with a standard care
group. The interventions comprised some form of relaxation
therapy that included PMR and guided imagery or visuali-
zation techniques. One trial 56
assessed autogenic training,
which provided training in relaxation meant to induce
heaviness and warmth of limbs, calming of the heart and
breathing, abdominal warmth, and cooling of the forehead.
Limitations of all of these trials included the potential for
expectation bias attributable to the inability to blind partici-
pants and a lack of attention control groups, although one
study used a health education attention control.78 Partici-
pants in these studies included patients with breast cancer
who had undergone or were currently undergoing surgery,
chemotherapy, or radiation therapy. The study sample sizes
ranged from 31 to 183 participants.
The majority of pertinent systematic reviews combine
relaxation techniques with stress-management, psychosocial,
and psychological interventions for patients with breast can-
cer. Thus, a review specific to relaxation interventions that
includes PMR and guided imagery for depression/mood or
other psychological outcomes in patients with breast cancer
and survivors is warranted. A review of studies of guided
imagery as adjuvant cancer therapy broadly assessed 6 RCTs
and found the methodological quality inconsistent.337
Across trials, the results provided few details, and the stud-
ies were implemented with heterogeneous cancer popula-
tions, interventions, and outcome measures, which
ultimately precluded statistical pooling of the results.
Despite these limitations, the results indicated that guided
imagery as a sole adjuvant cancer therapy was supportive
and increased comfort in patients and had few risks.
Beyond decreasing depression, relaxation therapy may
also have a beneficial impact on other symptoms important
to women with breast cancer. For instance, PMR was effec-
tive in ameliorating sleep problems and fatigue in women
undergoing chemotherapy for breast cancer. 338
Other likely
benefits attributable to this therapy in breast cancer popula-
tions include reduced nausea and anxiety.339-342
Risk/benefit assessment of relaxation interventions.
Relaxation therapy is noninvasive and positively engages the
patient with very little potential for harm. The goal of this
treatment approach is to use principles of psychoneuroim-
munology to better regulate the hypothalamic-pituitary-
adrenal axis, modulate cortisol production, and decrease
stress, which may have other health benefits, including psy-
chological outcomes that may be affected by stress and dis-
tress (such as anxiety and depression/mood disturbances).
Some of the appeal of relaxation therapy includes its low
cost, safety, and portability. With adequate training,
patients themselves can apply this therapy when and where
they want without the need for supervision. However, the
durability of relaxation therapy and the frequency required
to sustain a long-term positive effect on depression remain
unclear. It seems that relaxation therapy is not only applica-
ble for those with breast cancer and depression but also has
been shown to be beneficial in other contexts, including the
ability to decrease depression in adults343,344 and depression
associated with cardiac disease.345 The minimal cost and
low potential for harm with relaxation therapy, in conjunc-
tion with its evidence of benefit, support an A grade recom-
mendation for depression.
Future research in relaxation interventions for depres-
sion/mood. In addition to the gaps in the literature
described above, future research on the use of relaxation
interventions to improve mood disturbances should focus
on how to use novel electronic communication strategies to
deliver low-cost relaxation techniques to diverse patient
populations.
Yoga (B grade)
Overview of yoga interventions for depression/mood dis-
turbances. Yoga is recommended for improving mood dis-
turbances and depressive symptoms in women with breast
CA CANCER J CLIN 2017;67:194–232
VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 211
cancer (grade B). This recommendation is based on the
results from 15 RCTs, completed between 2006 and 2015,
that used a yoga intervention to reduce physical symptoms
and psychological distress, including depression (see Sup-
porting Information Table 3). 40-43,45-48,79-85
Depression or
depressive symptoms were the primary or secondary out-
come for all studies included in this review. Study partici-
pants included women recently diagnosed with or having a
recurrence of breast cancer; women who were receiving radi-
ation therapy, chemotherapy, or a combination of both; an
ethnically diverse and underserved sample of female
patients; and women who had completed breast cancer
treatment. Five different yoga interventions were tested in
study samples ranging in size from 23 to 200 participants.
Five trials assessed an intensive, integrated yoga program
that was customized for patients with breast cancer, includ-
ing asanas, pranayama, and yoga nidra. 41-43,81,85
Five trials
implemented Iyengar yoga, a traditional form of Hatha
yoga, and passive backbends.45,80,82-84 Two trials assessed
Patanjali’s yoga sutras, which included warm-up movements
synchronized with breathing, selected postures, deep relaxa-
tion techniques, meditation, and alternate-nostril breathing
(pranayama) 48,79
; while 2 trials evaluated only the pra-
nayama practices.46,47 Finally, a yoga exercise intervention
implemented meditation and breathing exercises that
focused attention on internal body sensations as well as yoga
exercises (modified asanas) composed of gentle stretching
and strengthening exercises. 40
It has been shown that yoga is beneficial for reducing
depression in a wide variety of clinical populations, 332,346-348
and specifically among individuals with cancer.325-328 One
meta-analysis investigating the impact of yoga interventions
on psychological health outcomes 329
analyzed 8 trials of
yoga interventions for depression and showed improvement
in depressive symptoms in the yoga groups compared with
the control groups (P 5 .002) among a heterogeneous sam-
ple of patients. Specifically in patients with breast cancer
and in breast cancer survivors, a meta-analysis330 of 12
RCTs, representing a total of 742 participants, revealed
short-term effects of yoga interventions on improved psy-
chological health, including depression (P < .01). A caveat
was that the observed efficacy was only applicable for yoga
practiced during active cancer treatment and not necessarily
in the post-treatment period. Overall, the authors stated
that, based on these positive preliminary results, yoga thera-
py should be used in this population.
Risk/benefit assessment of yoga interventions. The risk/
benefit assessment of the effects of yoga on depression and
mood disturbance outcomes is similar to the assessment
for anxiety outcomes. Studies assessing yoga for psychologi-
cal outcomes in individuals with cancer are typically
small, not well controlled, and preliminary in nature.
Furthermore, comparability across studies is difficult,
because findings differ between populations from
India41-43,85 and North America.45,46,48,82-84 Despite these
limitations, the evidence suggests that yoga interventions could
be added to treatment plans or in the post-treatment period,
provided these interventions are facilitated by appropriately
trained yoga instructors and can be adapted and modified for
people with medical conditions or limited mobility. 333
Future research in yoga interventions for depression/
mood. Future trials of yoga interventions to improve mood
disturbances/depression should test the effects of different
types, doses, and durations of yoga on patient populations
with various degrees and types of mood disturbances and
depression in addition to including larger sample sizes and
testing across active controls.
Massage (B grade)
Overview of massage therapy interventions for depres-
sion/mood disturbances. Massage therapy is recom-
mended to improve mood disturbance in breast cancer
survivors after active treatment (ie, surgery, chemotherapy,
radiation; grade B). This recommendation is based on
results from 6 trials completed between 2004 and
2012.53-55,86-88 In the trial reported by Listing et al,87 the
primary outcomes focused on physical discomfort and
fatigue, with mood disturbance as a secondary outcome.
The other 5 trials assessed depression as the primary out-
come and had other secondary outcomes, including per-
ceived stress, QOL, pain, heart rate variability, and emesis.
In the 5 trials, the effect of massage therapy was compared
with the effect of standard care. The studies, which took
place in the United States,53 Germany,54,86,87 England,55
and Spain, 88
all included breast cancer survivors who had
completed active cancer treatment at least 3 months before
study enrollment. The study sample sizes ranged from 20 to
288 participants. In 3 of the 6 trials, the massage therapy
intervention was a variation of classic massage involving
rhythmic stroking, kneading, and acupressure at select areas
on the body. 54,86,87
The study by Fernandez-Lao used an
experienced and trained physical therapist to administer
manual massage therapy. 88
Wilkinson et al 55
included aro-
matherapy as part of the massage therapy, which was indi-
vidualized across study participants. Hernandez-Reif et al53
combined massage with acupressure and Trager, which uses
hundreds of small, rocking, and elongating movements that
release muscle tension. The number and frequency of mas-
sage therapy sessions varied across the studies.
All of the trials assessing classic massage therapy used the
same protocol of biweekly, 30-minute massages for 5
weeks, 54,86,87
with the exception of the trial by Fernandez-
Lao et al, in which a one-time, 40-minute massage session
was assessed. 88
Across these studies, compared with control
Integrative Therapies During and After Breast Cancer Treatment
212 CA: A Cancer Journal for Clinicians
groups, women in the intervention groups reported signifi-
cant improvement in mental health outcomes, including
reduced depression and mood disturbance scores particularly
in relation to anxious depression, anger, and tiredness.
These differences between groups, however, were not con-
sistently sustained across all studies. For example, in the
study by Fernandez-Lao et al, the improvements in depres-
sion outcomes with a single-session massage intervention
depended on the participant’s individual level of enthusiasm
for that intervention. The classic massage studies54,86,87 and
one trial that combined massage with aromatherapy 55
found
that the massage interventions significantly decreased
depression only immediately after the intervention but not
long term. The remaining study that combined massage
therapy with acupressure and Trager53 demonstrated a posi-
tive effect of the interventions on anxiety and depression,
with these effects sustained at long-term follow-up.
A systematic review and meta-analysis examined the role
of massage interventions in the management of treatment-
related side effects associated with breast cancer in terms of
improvement in overall QOL, including measures of
depression. 349
In total, 18 RCTs were included in this
review. Overall regular massage therapy was shown to have
positive effects on other outcomes, such as anger and fatigue
symptoms, but the meta-analysis of 8 trials, 3 of which are
summarized in this section,53,54,87 did not find significant
beneficial effects of massage therapy for depression. Howev-
er, that meta-analysis was limited by significant heterogene-
ity across the studies that assessed depression as the
outcome (P 5 .002) as well as by small and possibly under-
powered sample sizes, which may have accounted for the
nonsignificant results. An earlier systematic review of mas-
sage therapy in breast cancer populations that found no pos-
itive effect of massage on depression also concluded that few
rigorous trials have been conducted and that the risk of bias
in such trials is high. 350
Risk/benefit assessment of massage therapy interven-
tions. Classic massage is a noninvasive therapy that has lim-
ited adverse effects. For patients with cancer, massage
therapy by a trained massage professional appears to have
few risks and may reduce pain, promote relaxation, and
boost mood, at least in the short term.351 Since trained,
licensed therapists delivered the interventions tested in these
studies, the recommendation of massage for depression
applies specifically to massage by trained therapists.352,353
Some caution is needed, however, for individuals receiving
anticoagulation therapy because of their risk of bruising.
Women with breast cancer who have undergone radiation
therapy or surgery or have implanted medical devices also
may need to be cautious in having massage to the affected
regions. In addition, some women may be reluctant to dis-
robe because of altered body image, modesty, or
ethnocultural issues. Thus, important considerations include
appropriate draping of the individual and ensuring that the
massage therapist is sensitive to the treatment experiences of
women with breast cancer and develops a therapeutic rela-
tionship with the individual. Ensuring that the massage
therapist is the same gender as the patient is considered best
practice in the massage profession and may also increase an
individual’s comfort with receiving massage therapy. How-
ever, this practice was not tested in the studies included in
this review.
Future research in massage interventions for depres-
sion/mood. A 2008 systematic review of massage therapy
for depression in the general public concluded that evidence
to support massage as an effective treatment for this indica-
tion and population was lacking.354 However, a more recent
(2010) meta-analysis of 17 RCTs concluded that massage
therapy had a positive effect on individuals suffering from
depression. 355
That meta-analysis also highlighted the het-
erogeneity across massage therapy trials in terms of therapy
protocols, outcomes measurement, and populations and
underscored the need for standardization across future mas-
sage therapy trials. These issues are also true for the trials
assessing massage interventions for depression/mood in
patients with breast cancer. Future research on massage
therapy interventions to improve depression/mood distur-
bances should focus on understanding how best to dissemi-
nate cost-effective massage interventions in routine clinical
settings.
Music therapy (B grade)
Overview of music therapy interventions for depression/
mood disturbances. Passive music therapy is recommended
to improve depression/mood disturbances in patients with
newly diagnosed breast cancer (grade B). This recommenda-
tion is based on 4 RCTs, completed between 2000 and
2011, that tested a music therapy intervention to improve
mood/depression (see Supporting Information Table
3). 33,35,89,90
Depression/mood disturbances were assessed
either as the primary outcome or as a secondary outcome to
anxiety. In all 4 trials, a music therapy intervention group
was compared with either a waitlist or a standard care con-
trol group. Study participants included women with a breast
cancer diagnosis who had completed mastectomy, chemo-
therapy, or radiation therapy or who had metastatic disease.
The study sample sizes ranged from 8 to 170 participants.
Three trials examined the effect of passive music therapy,
which was found to decrease depression scores compared
with controls,35,89,90 and the fourth trial examining active
music therapy 33
yielded no clinically meaningful, long-term
effects between groups or over time. Active music therapy
resulted in immediate effects on happiness within the
intervention group that were not sustained over time.
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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 213
Therefore, the guideline recommendation is specific to pas-
sive music therapy.
Of the 5 studies combined in the meta-analysis described
above that assessed multiple types of art therapies for
improving anxiety, depression, and QOL among patients
with breast cancer322 (4 music therapy interventions, includ-
ing 2 trials identified in our review,33,204 and an art therapy
trial), a clinically and statistically significant mean difference
(P 5 .05) was observed across all depression scores in the
music therapy intervention groups compared with control
groups. Furthermore, a systematic review of music therapy
specifically for depression in the Cochrane Database of Sys-
tematic Reviews found that, although only 5 RCTs have
tested music therapy interventions for depression and have
met the review study inclusion criteria, this therapy is widely
accepted and beneficial to a broad range of individuals with
depression and is associated with improvements in mood
disturbances.356 Taken together, this literature supports our
recommendation of passive music therapy for reducing
depression and improving mood.
Risk/benefit assessment of music therapy interventions.
The risk/benefit assessment of passive and active music
therapy interventions for depression/mood among patients
with breast cancer is the same as that for anxiety depression
(see above).
Future research in music therapy interventions for
depression/mood. Future research in this area should
assess long-term effects of passive music therapy on mood
disturbances/depression, because the reviewed trials were
limited to assessing short-term improvement of mood/
depression after breast cancer treatments or during meta-
static cancer diagnosis. In addition, studies should attempt
to replicate the null findings of active music therapy inter-
ventions to formulate a comprehensive risk assessment
regarding active music therapy. Suggestions for future
research in music therapy for improving depression/mood
are similar to those for anxiety, as stated above (see Use of
Integrative Therapies for Anxiety/Stress Reduction).
C-graded therapies for depression/mood
Acupuncture,49-51,91,92 healing touch,93,94 and stress man-
agement36-38,95,96 can be considered for improving mood
and depressive symptoms (grade C). Five trials assessed acu-
puncture as a treatment for depression/mood (but as a sec-
ondary outcome), and only one trial was large, 51
with mixed
findings in terms of effect. Two studies assessed the effect
of healing touch on depression as a primary outcome, with
one small study showing no effect94 and a larger study
showing a positive effect.93 Although 5 large studies were
reviewed for the effect of stress management on depression/
mood, the findings were inconclusive because of inconsis-
tent results across trials. Future research directions should
include conducting trials with larger samples sizes and repli-
cating trials with these modalities to examine their impact
on depression symptoms and improving mood as the prima-
ry outcome.
Use of Integrative Therapies for Fatigue
Description of fatigue
Among patients with cancer, fatigue is commonly referred
to as cancer-related fatigue. Fatigue is a multifactorial con-
dition marked by extreme tiredness and an inability to func-
tion because of lack of energy.357 According to National
Comprehensive Cancer Network guidelines, ratings of
fatigue of 4 or higher on a scale from 0 to 10 (where 10 is
very severe fatigue) are further evaluated for known contrib-
uting factors, such as pain, emotional distress, anemia, sleep,
nutrition, and level of activity. These comorbidities are then
treated. The CTCAE measures fatigue from grade 1
(relieved by rest) to grade 3 (not relieved by rest, limiting
activities of daily living). Fatigue is the most frequent and
distressing side effect of common antineoplastic therapies,
including chemotherapy, radiation therapy, surgery, and
selected biologic response modifiers. 196
Although cancer-
related fatigue typically improves upon the conclusion of
treatment, it can last for months or years in up to one-third
of patients and may become a chronic condition that leads
to a variety of physical and psychological effects long into
survivorship. Symptoms of fatigue include feeling tired,
weak, worn-out, heavy, slow, or having “no energy or get-
up-and-go.” Cancer-related fatigue is different from com-
mon tiredness in both its magnitude and quality. Cancer-
related fatigue is not typically relieved by rest and is much
more profound than simply feeling tired. About 33% of
patients with breast cancer experience moderate to severe
fatigue. 358-360
Fatigue has disruptive consequences and can
have a negative impact on a patient’s QOL, mood, and self-
esteem. 192
Cancer-related fatigue can prevent patients from
taking part in daily activities, relationships, social events,
community activities, as well as work or school, which can
have financial consequences, such as loss of employment
and health insurance.
C-graded and D-graded therapies for fatigue
There are no A-graded or B-graded therapies to report for
fatigue. Trials evaluating hypnosis, 97,98
ginseng, 99,100
acetyl-
L-carnitine, 107
and guarana 108,109
have examined their
effects on fatigue during treatment. Two trials from a single
research group reported beneficial effects of hypnosis on
fatigue during treatment; therefore, hypnosis can be consid-
ered for fatigue during treatment (grade C). Neither acetyl-
L-carnitine nor guarana is recommended for improving
fatigue during treatment because of a lack of effect in clini-
cal trials among patients with cancer (grade D for both).
Ginseng received a grade C for fatigue during treatment
Integrative Therapies During and After Breast Cancer Treatment
214 CA: A Cancer Journal for Clinicians
based on a single, high-quality trial with a large sample
size.99 A previous large, high-quality, dose-finding study by
the same group indicated that a higher dose was more effec-
tive.100 In subset analyses in the subsequent trial, which
tested the receipt of ginseng by patients who reported
fatigue either during or after treatment, the results showed
that ginseng was more effective in patients undergoing
active treatment. Trials testing the effects of acupunc-
ture51,101-103 and yoga45,80,84,104-106 for post-treatment
fatigue yielded modest results (grade C). Four high-quality
acupuncture trials assessed fatigue as the primary outcome;
3 of those 4 trials included a large sample size.51,101-103 Acu-
puncture for post-treatment fatigue received a grade of C
mainly because of inconsistent comparison groups across the
trials, including sham acupuncture,101,103 standard of
care,51,102 self-administered acupuncture,102 and wait-list
control.103 Three trials evaluated yoga for post-treatment
fatigue as a primary outcome45,80,106; only one study had a
large sample size80 and the other 2 reported contrasting
results.45,106
Use of Integrative Therapies for QOL
Description of QOL
QOL is a multidimensional construct that typically mea-
sures the functioning of emotional, physical, role, and social
domains using validated questionnaires. 361
The majority of
patients with breast cancer report some level of diminished
QOL during cancer treatment and/or survivorship. 362
The
physical domain includes common physical side effects of
cancer and cancer treatment, including constipation and
diarrhea, fatigue, hair loss, fever, hot flashes and night
sweats, lymphedema, nausea and vomiting, poor nutrition,
oral complications, pain, and skin changes, as well as the
ability to function physically in everyday life. The emotional
domain includes psychological functioning with indicators
of anxiety, depression, distress, confusion, and memory
problems. The sexual functioning domain refers to patients’
perception of sexuality and sexual functioning, attractive-
ness, and fertility. Finally, the social domain refers to the
patients’ social functioning, their social role, and level of
social support. Each of the domains, either individually or
in combination, influences a patient’s QOL. 302,363-365
Dec-
rements in QOL may persist upon the conclusion of treat-
ment, during chronic/long-term hormonal and biotherapies,
and into survivorship.366
Meditation (A grade)
Overview of meditation interventions for QOL. Medita-
tion is recommended for improving QOL in patients with
breast cancer (grade A). This recommendation is based on 7
RCTs, completed between 2009 and 2013, which used
meditation for this indication (see Supporting Information
Table 4). 27-29,73-75,127
QOL was the primary outcome in 4
of those 7 trials.73-75,127 In 4 trials,27-29,74 a meditation inter-
vention group was compared with a usual care or waitlist con-
trol condition group, and 3 other trials73,75,127 used a 3-arm
design. Study participants included women undergoing radia-
tion therapy for breast cancer, patients with newly diagnosed
stage 0 through IV breast cancer, breast cancer survivors who
had completed treatment, and older adult breast cancer survi-
vors aged 55 years and older. The study sample sizes ranged
from 47 to 180 participants. These trials overlap with the trials
described under meditation interventions for anxiety/stress
reduction and depression outcomes (see above).
Previous research has supported the role of MBSR inter-
ventions for improved QOL in heterogeneous samples of
patients with cancer and survivors, with effect sizes ranging
from small to large on QOL scales.319,367,368 One review in
particular assessed the impact of MBSR on QOL in
patients with breast cancer.175 In that review, the authors
identified only 3 studies that met their criteria and also mea-
sured QOL as an outcome. 29,127,292
Of the 3 studies that
measured QOL, only one (also included in our review)
reported significant improvements after MBSR interven-
tion 29
relative to results in control or comparator groups.
The other 2 trials reported no significant improvements in
QOL after MBSR intervention or at follow-up. A second
systematic review and meta-analysis was conducted to inves-
tigate the effect of MBSR in the cancer care setting on sev-
eral psychological outcomes, including QOL. 316
The
analyses specific to the QOL outcome included 248 patients
in 6 studies and reported a small effect size (P < .01). The
authors suggest that, although these findings support the
use of MBSR for improving QOL, more well conducted
RCTs are required that implement adequate controls, lon-
ger follow-up periods, larger sample sizes, and obtainment
of patients’ psychological profiles.
Risk/benefit assessment of meditation interventions
There is very little risk to participants who use meditation
therapies to improve QOL and/or physical functioning.
Few adverse events have been reported in any trials involv-
ing meditation, with participants typically reporting positive
feedback about meditation, resulting in low dropout rates
from the programs. Group meditation formats and online
and home-based adaptations of MBIs321 are cost-effective
and beneficial therapies that can be used as adjuncts to tra-
ditional individual counseling or psychotherapy.
Future research in meditation interventions for QOL. To
improve specificity of the effective components of medita-
tion and to compare meditation interventions with other
MBIs, research assessing meditation as a treatment for
improved QOL and/or physical functioning should be
extended to directly compare meditation with other forms
of therapy, including individual counseling, cognitive
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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 215
behavioral therapy, and other MBIs, similar to the therapies
compared in the trial by Carlson et al.26
Yoga (B grade)
Overview of yoga interventions for QOL. Yoga is recom-
mended for improving QOL in patients with breast cancer
(grade B). This recommendation is based on 12 RCTs,
completed between 2006 and 2015, which tested a variety
of yoga programs (see Supporting Information Table
4).43,46-48,82-85,104-106,128 QOL was the primary outcome for 6
of those 12 trials.47,82,83,105,106,128 In 10 trials, a yoga interven-
tion group was compared with a usual care or waitlist control
condition group, and 2 other trials used brief supportive therapy
as a comparison group.43,85 Study participants included women
undergoing radiation therapy or chemotherapy for breast cancer,
patients with newly diagnosed breast cancer, and breast cancer
survivors who had completed treatment. The study sample sizes
ranged from 15 to 128 participants. Several of these trials over-
lap with those described under yoga interventions for anxiety
and depression outcomes (see above). In total, 4 different types
of yoga interventions were investigated, including: Iyengar or
Hatha yoga,82-84,104-106 an integrated yoga program,43,85,128 pra-
nayama or yoga breathing,46,47 and Patanjali’s yoga sutras.48
Another systematic review and meta-analysis assessed the
impact of yoga interventions on QOL and psychological
health specifically in patients with breast cancer and survi-
vors.330 Overall, 12 RCTs were included in that analysis
with a total of 742 participants. Analyses revealed short-
term effects on improved psychological health, including
anxiety (P < .01), perceived stress (P 5 .03), and psycholog-
ical distress (P < .01). However, it is notable that these
effects were only applicable to those who engaged in yoga
during active cancer treatment and not in the post-
treatment period. The authors state that, with these positive
preliminary results, yoga should be used in this population.
Risk/benefit assessment of yoga interventions. As stated
above regarding yoga for anxiety/stress and for depression/
mood disturbances, yoga can be adapted and modified for
use in this population with low risk to the patient. Overall,
yoga has shown preliminary efficacy in improving QOL and
is recommended for use in patients with breast cancer.
Future research in yoga interventions for QOL. As also
stated above, future trials of yoga to improve QOL/physical
functioning should examine the effects of different types,
doses, and durations of yoga on QOL outcomes. Higher
quality trials, including trials with larger and more diverse
samples, should be conducted.
C-graded and D-graded therapies for QOL
Trials in acupuncture,49,51,102,129,130 mistletoe,131-134
qigong,135,136 reflexology,137-139 and stress manage-
ment36-38,95,96,140,141 have assessed the effect of these
therapies on QOL and received a grade of C, indicating that
they can be considered for use. The 5 trials evaluating
acupuncture had mixed findings and small sample sizes; future
studies should replicate the trials of acupuncture that
compared real versus sham acupuncture, which were the study
designs that produced no effect.49,102 Two trials135,136 found
that qigong had beneficial effects on QOL; however,
those studies were fairly small and should be replicated in
larger and more diverse patient populations. Three large,
high-quality trials137-139 of reflexology for improving QOL
reported mixed findings. The trials of stress management had
conflicting results and used a broad range of control
groups.36-38,95,96,140,141
There is some evidence that mistletoe may improve QOL
in patients with breast cancer.131-134 However, although the
trials have study quality and sample sizes that could merit a
grade of B, the final decision to assign a grade of C is
because of 2 areas of uncertainty. First, while several differ-
ent preparations and formulations have been found to be
effective in trials of moderate size, the assessment does not
result in a higher grade because of the nonspecificity and
variability in formulations of the agents tested. Second,
mistletoe is an injected bioactive compound with a potential
for a differential risk/benefit ratio because of toxicities and
drug interaction with standard cancer therapies that may not
be detected in smaller studies; a similar stringency need not
to be applied to MBIs, because they have lower risk profiles.
The grade C recommendation is based on 4 RCTs, complet-
ed between 2004 and 2014, which tested the use of mistletoe
for improving QOL.131-134 QOL was the primary outcome
in all 4 trials in which a mistletoe product group was com-
pared with a placebo 131,132
or standard care 133,134
control
group. The mistletoe products tested, all of which injected
subcutaneously, included PS76A2,131,132 Helixor A,134 and
Iscador.133 Study participants included women who were
receiving chemotherapy for breast cancer, and sample sizes
ranged from 61 to 352 participants. To improve specificity
of the effectiveness of mistletoe as a treatment for improved
QOL in patients with breast cancer, double-blind trials need
to directly evaluate and compare the different products
available and also should assess long-term benefit and safety
from the use of mistletoe products. Trials of bioactive agents
carry the additional requirement of adequate size and
statistical power to exclude drug interactions and attenua-
tion of cancer outcome benefits of concurrently adminis-
tered, adjuvant treatments. Two systematic literature
reviews 178,369
of controlled clinical trials of mistletoe,
including a Cochrane database analysis, did find an
improvement in survival in the adjuvant setting. Although
this outcome was outside the scope of this current review,
the 2 reviews suggested a QOL benefit and called for
further confirmatory trials. 178,369
Integrative Therapies During and After Breast Cancer Treatment
216 CA: A Cancer Journal for Clinicians
Use of Integrative Therapies for CINV
Description of CINV
CINV is experienced by some patients with cancer after
they receive chemotherapy.197,370,371 Acute CINV is typi-
cally defined as occurring during the first 24-hour period
after chemotherapy administration. It is believed that
delayed or late CINV is mediated by different mechanisms
compared with acute CINV372 and occurs more than 24
hours after chemotherapy administration. In a large, pro-
spective study of patients with breast cancer who were
receiving chemotherapy, 37% reported any nausea, and 13%
reported any vomiting during the first 24-hour period. 373
In
the 2 to 5 days after chemotherapy administration, 70%
reported any nausea, and 15% reported any vomiting.195,373
The consequences of CINV include dehydration, serious
metabolic derangements, nutritional depletion and anorexia,
deterioration of physical and mental status, withdrawal from
potentially useful and curative antineoplastic treatment, and
decreases in self-care and functional ability. CINV is con-
sidered to be one of the most severe and feared adverse
effects of cancer treatment by patients and can have a signif-
icant impact on QOL. 370,374-376
Standard of care antiemet-
ics for managing CINV have changed considerably in the
last 5 years, thus many of the trials evaluating integrative
approaches are not tested with the newest and most effective
standard treatment regimen. 197,371
Most contemporary
studies use as the endpoint the proportion of patients
achieving a complete response, defined as no emesis or use
of rescue medication. In addition, antiemetics themselves
have side effects, such as headaches, constipation, and neu-
ropsychiatric effects, and thus merit study designs that
replace medications with integrative approaches and use
equivalence or nonsuperiority designs for the CINV and
medication side-effect endpoints.
Acupressure (B grade)
Overview of acupressure interventions for CINV. For
patients with breast cancer who are receiving chemotherapy,
acupressure can be considered as an addition to antiemetics
to help control nausea and vomiting (grade B). This recom-
mendation is based on results from 3 RCTs, reported
between 2000 and 2007, of an acupressure intervention used
in conjunction with antiemetics to treat CINV (see Sup-
porting Information Table 5).61-63 Acute and delayed nau-
sea and vomiting were the primary outcomes for all 3 trials.
In 2 trials, 61,63
the acupressure plus usual care intervention
group was compared with a usual care group. The third tri-
al62 was a 3-arm trial comparing: 1) true acupressure at the
P6 and SI3 points in addition to usual care; 2) sham acu-
pressure, or placebo acupressure on a different acupressure
point, in addition to usual care; and 3) usual care only. (Of
note, the use of sham controls in acupressure and
acupuncture studies is an attempt to control for the experi-
ence of receiving the treatment; if it is implemented well,
participants will not be able to discern between the true and
sham techniques.) Study participants included patients with
breast cancer undergoing the first, second, or third cycle of
chemotherapy. The study sample sizes in the trials ranged
from 17 to 160 participants. The acupressure interventions
included self-acupressure61,62 using a finger and wearing
acupressure wristbands.63 Across the 3 trials, acupressure
therapy produced significant decreases in nausea, retching,
and vomiting (P < .05 for multiple outcomes assessing
CINV) (for details, see Supporting Information Table 5).
A review assessing acupressure as a nonpharmacologic
adjunctive intervention for CINV control across all cancers
concluded that acupressure should be strongly recom-
mended as an effective intervention along with standard
care for CINV control.377 Other studies of acupressure to
reduce nausea and vomiting have shown efficacy in other
populations, including pregnant women and postoperative
patients, including after thyroidectomy.378 All of these stud-
ies were conducted with acupressure wristbands placed on
both the patient’s arms at the PC6 acupoint.379 A review of
acupuncture and acupressure for CINV control among
patients with breast cancer concluded that the therapies are
both safe and effective.380 A secondary data analysis of the
multicenter study by Dibble et al 62
concluded that patients
with breast cancer whose nausea intensity started higher
from the acute phase continued to experience higher symp-
tom intensity during the 11 days after chemotherapy admin-
istration and required more frequent acupressure on
acupressure point PC6 even after the peak of nausea. 381
However, a recent publication by Molassiotis, a lead author
of one of the included trials in our review, and colleagues382
suggests an overall placebo effect in the study of acupressure
for control of CINV, although this interpretation included a
mix of cancer populations and was not limited to patients
with breast cancer.
Risk/benefit assessment of acupressure interventions.
Self-administered acupressure is easy to perform, safe, cost
effective, noninvasive, does not interfere with a patient’s pri-
vacy, and has no deleterious effects on patients. Acupressure
can be performed anywhere with little or no equipment.
Future research in acupressure interventions for CINV.
Future research in this area could assess how to identify the
best patients who can be instructed to perform self-
administered acupressure, when acupressure can be per-
formed, and whether additional points can be administered
along with PC6 to increase the effectiveness of self-
administered acupressure to reduce nausea and vomiting.
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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 217
Electroacupuncture (B grade)
Overview of electroacupuncture interventions for CINV.
Electroacupuncture or acustimulation can be considered as
an addition to antiemetics to control CINV in patients with
breast cancer during chemotherapy (grade B). This recom-
mendation is based on 2 RCTs, published in 2000 and 2012
(see Supporting Information Table 5),64,65 as well as the
1997 National Institutes of Health Consensus Conference
on acupuncture.383 However, most of those trials predated
the use of newer agents, including, 5-hydroxytriptamine
type 3 (5-HT3) and neurokinin-1 (NK1) receptor antago-
nists, which have become standard antiemetic therapies for
patients who receive highly emetogenic chemotherapy. We
do not have a body of evidence to evaluate whether the
addition of acupuncture to contemporary antiemetics yields
added benefit. Participants in the trials in this analysis
included patients with breast cancer who had received mod-
erately high or highly emetogenic chemotherapy without a
5-HT3 or NK1 receptor antagonist.197 Both trials used
PC6 and ST36 acupoints and sham controls, and both trials
evaluated the effects of these acupoints on acute and delayed
CINV. One trial also used acupoint LI4 and found that
electroacupuncture was no better than sham electroacupunc-
ture and that a likely contributor to the lack of effect of elec-
troacupuncture in CINV was the that the study evaluated
only feasibility with a minimal electroacupuncture interven-
tion and without a no-acupuncture arm. 64
The second trial
indicated that the patients receiving electroacupuncture
experienced significantly fewer emesis episodes over the 5
days of the acupressure intervention than the patients
receiving mock therapy or antiemetics alone (P < .001). 65
Between-group differences in the number of emesis epi-
sodes were also significant for electroacupuncture versus
minimal needling (P < .001) and for minimal needling ver-
sus antiemetics alone (P 5 .01).
A multicenter study by Yang et al384 that compared ST36
electroacupuncture plus antiemetics with antiemetics alone
in 246 patients with heterogeneous cancers indicated an
additive effect with the use of electroacupuncture (P < .01),
with greater decreases in nausea and vomiting scores (P <
.001) compared with the use of antiemetics alone. Two early
studies by Dundee and colleagues385,386 reported signifi-
cantly less CINV with a PC6 electroacupuncture interven-
tion, although the investigators noted that the brevity of
emetic action was a major problem. In a recent review of
acupuncture studies, including those that evaluated CINV,
investigators concluded that only the electroacupuncture
study by Shen et al65 had a low risk of bias.160 In addition,
an earlier meta-analysis by Ezzo et al387 determined that
electroacupuncture, but not manual acupuncture, was bene-
ficial for first-day vomiting and that needle insertion as part
of manual and electroacupuncture provides greater intensity
of stimulation and produces more beneficial effects than sur-
face electrostimulation.
Risk/benefit assessment of electroacupuncture interven-
tions for CINV. With proper administration, electroacu-
puncture has been shown to be both safe and
effective. 119,388-392
In addition to possibly reducing CINV,
PC6 stimulation has been associated with other positive
benefits, including analgesic,119 sedative,393 and anxiolytic
effects.394 Furthermore, because CINV is drug-specific
rather than disease-specific, these benefits should extend to
CINV in other cancer patient populations, as suggested in
the study by Yang et al, 384
with participants who had a vari-
ety of cancers. Practical issues to consider are that electroa-
cupuncture should not be used in patients with a pacemaker
or implantable defibrillators and that special attention is
required when treating patients who are pregnant, have sei-
zure disorders, or are disoriented.160
Future research in electroacupuncture interventions for
CINV. Future trials on the use of electroacupuncture inter-
ventions for CINV in patients with breast cancer can focus
on testing the use of electroacupuncture with new standard-
of-care treatment regimens as well as the dissemination and
implementation of this technique in the clinical setting. In
addition, nausea that is unrelated to chemotherapy is also a
common problem in patients with cancer, and this modality
could be tested and compared with less potent antiemetics
or best supportive care when other therapies are ineffective.
C-graded and D-graded therapies for CINV
Three trials of ginger 66-68
and 2 trials of relaxation 59,69
have
examined their effects on CINV as a primary outcome.
Although the number of trials was limited, the results sug-
gested enough of an effect to result in a grade C recommen-
dation stating that ginger and relaxation can be considered as
an addition to antiemetics for the control of acute CINV.
Future directions in research should focus on replicating trials
of these modalities for CINV as the primary outcome. Gluta-
mine is not recommended for improving CINV because of a
lack of effect from 2 trials70,71 in which CINV was assessed
as a secondary outcome (grade D).
Use of Integrative Therapies for Acute Radiation Dermatitis
Because radiation is a localized, targeted therapy, side effects
are most often locoregional within the targeted area. How-
ever, damage to normal local tissues and adjacent organs at
risk can result in fatigue as the body expends energy in nor-
mal tissue repair. The most common side effect in patients
with breast cancer is acute skin irritation. Late changes to
normal tissue can occur years after therapy and can include
soft tissue fibrosis, lymphedema, lung, and heart and chest
wall damage.395 Not all patients experience one or all of the
Integrative Therapies During and After Breast Cancer Treatment
218 CA: A Cancer Journal for Clinicians
side effects of radiation, but patients who do experience
acute side effects of radiation typically see the effects go
away several weeks after treatment.395 Acute radiation der-
matitis can occur with radiation therapy and may result in
reactions ranging from faint erythema; to dry, itchy, and
peeling skin; and ultimately to moist desquamation and
ulceration. 396
The Cooperative Group Common Toxicity
Criteria (CGCTC) is the most common scale to measure
acute radiation skin toxicity that is used by cooperative
groups during cancer clinical trials and grades skin reactions
from 0 to 4 with, grade 1 indicating erythema and grade 4
indicating ulceration. Most patients with breast cancer
develop mild-to-moderate acute skin reactions of grade 1
through 3 during and shortly after a course of radiation
therapy. These reactions usually resolve quickly but can
cause significant symptoms, especially with higher grade
toxicity.396
D-graded therapies for acute radiation dermatitis
There are no therapies graded A, B, or C to report for acute
radiation dermatitis after treatment. Aloe vera gel and hya-
luronic cream are not recommended as a standard therapy
to prevent or treat acute radiation dermatitis simply because
of lack of effect (grade D). Our review consisted of 2 quality
studies for each product with large sample sizes for both the
aloe vera 22,23
and hyaluronic cream 24,25
trials. Each trial
assessed the acute skin reaction from radiation therapy as its
primary outcome.
Use of Integrative Therapies for Vasomotor Outcomes
Vasomotor symptoms are common in patients with breast
cancer and include hot flashes, intense sweating, and flush-
ing on the face and chest, and they may come with heart
palpitations and anxiety. 397
These symptoms occur episodi-
cally, including nocturnally, when night sweats can signifi-
cantly disrupt women’s sleep. According to the NCI, about
two-thirds of postmenopausal women with a history of
breast cancer experience hot flashes. These symptoms may
occur naturally or as a consequence of surgery, chemothera-
py, or endocrine therapy.398 While vasomotor symptoms
may resolve on their own, 20% of affected women suffer
from persistent hot flashes 4 years after their last menses.397
Together, vasomotor symptoms can significantly impact
women’s QOL.398
C-graded and D-graded therapies for vasomotor outcomes
There are no A-graded or B-graded therapies to recom-
mend for vasomotor outcomes. Acupuncture can be consid-
ered as a therapy for hot flashes based on 9 trials that
assessed acupuncture for hot flashes (grade C). 49,91,92,143-148
Seven of those trials assessed hot flashes as the primary out-
come,91,92,143-146,148 and only one trial148 had more than
100 participants. Overall, the literature showed mixed find-
ings; however, the single, large trial demonstrated signifi-
cant reductions in hot flashes in their electroacupuncture
group compared with sham and control groups. The use of
soy as a therapy for hot flashes is not recommended because
of lack of effect (grade D). Three large trials149-151 assessed
soy for the treatment of hot flashes as the primary outcome
and showed a lack of effect.
Use of Integrative Therapies for Lymphedema
Lymphedema
Lymphedema is a condition after treatment, such as sur-
gery or radiation therapy, in which parts of the lymph sys-
tem become damaged or blocked, leading to an
accumulation of lymph fluid that does not drain properly,
builds up in tissues, and causes swelling. 166
The CTCAE
grades edema of the limbs from grade 1 (5%-10% interlimb
discrepancy) up to grade 3 (>30% interlimb discrepancy).
Lymphedema commonly affects the arm or leg but can also
impact other parts of the body. For patients with breast
cancer and survivors, lymphedema is most common in the
upper extremities and sometimes in the breast and/or chest
wall, and it can occur up to 30 years after treatment.
Because of differences in diagnosis, characteristics of the
patients studied, and inadequate follow-up, the overall
incidence of arm lymphedema after breast cancer reported-
ly ranges from 8% to 56%.399 Breast cancer survivors with
arm lymphedema in particular have been found to have
decreased QOL and increased psychological distress and
disability compared with survivors without
lymphedema. 399-401
C-graded therapies for lymphedema
There are no A-graded or B-graded therapies to report for
lymphedema. Two trials assessed low-level laser thera-
py,110,111 and 7 trials assessed manual lymphatic drain-
age112-118 for the treatment of lymphedema as a primary
outcome. The 2 trials that evaluated low-level laser therapy
were small in sample size and showed mixed findings. Only
2 of the 7 trials that assessed manual lymphatic drainage
had a sample size greater than 100 participants.113,118 Over-
all, the literature suggests that manual lymphatic drainage
and compression bandaging are equivalent. 114-116
Thus,
either therapy can be considered as treatment options for
lymphedema, with manual lymphatic drainage being con-
sidered for those who have sensitivity to bandaging (grade
C).
Use of Integrative Therapies for CIPN
CIPN
Cancer treatments, including chemotherapy, may cause
damage to the peripheral nerves, resulting
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VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 219
in neuropathy.402 The CGCTC categorizes neuropathy
under neurologic-sensory and grades it from 0 to 3, with 3
indicating severe objective sensory loss or paresthesias that
interfere with function. Sensory neuropathy can include
symptoms of pain, tingling, numbness, or a pins-and-
needles feeling, the inability to feel a hot or cold sensation,
or the inability to feel pain. Motor neuropathy can include
problems with balance, weak or achy muscles, twitching,
cramping or wasting muscles, and swallowing or breathing
difficulties. Autonomic nerve damage can cause dizziness
or faintness and digestive, sexual, sweating, and urination
problems.402
H-graded therapies for CIPN
There are no A-graded or B-graded therapies to report for
the prevention or treatment of CIPN. Acetyl-L-carnitine is
not recommended as a standard therapy to prevent or treat
CIPN because of harm (grade H). A single, large, high-
quality study107 assessing the use of acetyl-L-carnitine cap-
sules to prevent CIPN after taxane therapy as a primary out-
come found that acetyl-L-carnitine administered during
taxane chemotherapy was associated with worse CIPN
symptoms.
Use of Integrative Therapies for Pain
Pain
According to the International Association for the Study of
Pain, pain can be defined as “an unpleasant sensory and
emotional experience associated with actual or potential tis-
sue damage.”403 The CTCAE grades pain from 1 (mild) to
3 (severe, limiting self-care). Pain can be caused by cancer
therapies, including surgery, radiation therapy, chemothera-
py, targeted therapy, supportive care therapies, and/or diag-
nostic procedures. 404
Pain is commonly experienced by
patients who have breast cancer with a prevalence ranging
from 40% to 89%. 403
Pain management requires proper
assessment, including measurement of intensity. 404
It is also
important to evaluate the impact of pain on the patient’s
physical, mental, and social health, because pain can nega-
tively impact their functional status and QOL. Pain man-
agement can include both pharmacologic and
nonpharmacologic modalities. Proper education about treat-
ment and longitudinal follow-up are essential.
C-graded therapies for pain
There are no A-graded or B-graded therapies to report for
pain. Healing touch93 for pain after chemotherapy; music
therapy,31,34 hypnosis,125,126 and acupuncture119 for pain
after surgery; and acupuncture 120-124
for pain related to aro-
matase inhibitor-associated musculoskeletal symptoms were
examined, and each received a grade of C, indicating that
they can be considered as a therapy for pain. A single, large
trial assessed healing touch93 for pain after chemotherapy as
a secondary outcome and demonstrated small positive
effects favoring the therapy. Similarly, trials that assessed
music therapy,31,34 hypnosis,125,126 and acupuncture119 for
pain after surgery as a primary outcome demonstrated small
positive effects favoring the therapy. However, there is a
lack of multiple, large trials to support each therapy. Finally,
5 trials evaluated acupuncture for pain related to aromatase
inhibitor-associated musculoskeletal symptoms as the pri-
mary outcome. 120-124
All of those trials had small sample
sizes and reported mixed findings.
Use of Integrative Therapies for Sleep Disturbance
Sleep disturbances
Studies have shown that nearly one-half of all patients with
breast cancer have sleep-related problems from a range of
causes, including side effects of antineoplastic medications,
long hospital stays, or stress.405,406 In addition, growing
numbers of patients with breast cancer are obese,407 which
increases the incidence of sleep apnea, a major cause for
insomnia. Insomnia, a specific sleep disorder of initiating
and maintaining sleep, is most common in patients with
cancer and often occurs along with anxiety and depres-
sion. 408
The CTCAE measures insomnia under psychiatric
disorders from grade 1 through grade 3, with grade 3 indi-
cating severe difficulty falling asleep, staying asleep, or wak-
ing up early.
C-graded therapies for sleep disturbance
There are no A-graded or B-graded therapies to report for
sleep disturbance. Yoga can be considered for sleep distur-
bance (grade C). Five trials assessed yoga for sleep distur-
bance45,48,79,84,172; and, in 4 of those trials, sleep was a
secondary outcome. Two trials were of high quality, with
more than 100 participants.79,142 Overall, the body of litera-
ture showed no greater effect on sleep quality for health
education classes, stretching groups, and wait-list controls.
Conclusion
In this review, we closely examined and described the RCTs
that provide support for the highest graded therapy recom-
mendations for the use of integrative therapies during the
patient experience of breast cancer and for side effects relat-
ed to breast cancer treatment. High levels of evidence sup-
port the routine use of mind-body practices, such as yoga,
meditation, relaxation techniques, and passive music thera-
py, to address common mental health concerns among
patients with breast cancer, including anxiety, stress, depres-
sion, and mood disturbances. In addition, it has been dem-
onstrated that meditation improves QOL and physical
functioning; yoga improves QOL and fatigue; massage
improves mood; and acupressure and electroacupuncture
decrease CINV. Given the high level of evidence of benefit
Integrative Therapies During and After Breast Cancer Treatment
220 CA: A Cancer Journal for Clinicians
coupled with the relatively low level of risk, these therapies
can be incorporated as an option into patient care, especially
when there is poor symptom control. As is the case with
many standard therapies, the impact of integrative
approaches on symptom management is highly individual-
ized. Therefore, a patient-centered trial and evaluation
approach may be needed and can be guided by the grade of
recommendations and altered as needed along with the
incorporation of patient preferences. In addition to the
modalities discussed in this review that were given a lower
grade (C or D), patients are using many other forms of inte-
grative therapies with little or no supporting evidence; this
serves as a compelling call for further research to support
patients and health care providers in making more informed
decisions that avoid harm. In the meantime, while further
clinical evaluation is underway, clinicians and patients need
to be cautious about the use of therapies that received a
grade of C or D and need to fully understand the potential
risks and benefits of use, including the risk associated with
not using a conventional therapy that may effectively pre-
vent or treat the condition. For example, in a patient with
incurable disease who has marked symptoms not adequately
managed with conventional therapies, carefully monitored
use of a grade-C therapy could be medically reasonable,
although more research clearly would be needed to apply
this broadly across a patient population. This review and
others support referral or provision of clinical services to
include both evidence-based conventional and integrative
therapy options.
The limited numbers of integrative modalities with
grades of A or B emphasize the need for all cancer care pro-
viders to initiate a dialogue early in their relationship with
patients to develop a framework for how evidence forms the
basis for all clinical decisions. Patients and clinicians should
engage in shared decision making based on the best avail-
able evidence on the benefits and harms while reflecting
patient values and preferences. A careful appraisal of the evi-
dence base for integrative therapies can help allay a patient’s
concern that their care team is informed and is not over-
looking options that may be of interest to them. In addition,
such an appraisal of the evidence will offer those modalities
that do merit consideration and allow for better personaliza-
tion of care and shared decision making.
This systematic review with grades of evidence adds to a
growing literature base that includes reviews of integrative
therapy for patients with breast cancer and other cancer
populations. For example, numerous reviews support the
use of integrative therapies, including passive music thera-
py,322 stress-management programs,324 various yoga practi-
ces,329 meditation and MBSR,315 massage,349 and
relaxation techniques, 337
as adjunctive therapies for psycho-
logical outcomes, specifically the anxiety/stress and
depression/mood outcomes assessed in this review. Acupres-
sure for CINV is also well supported in the review literature
across all populations of patients with cancer. 377
There are
mixed findings in the areas of meditation and MBSR for
QOL 175,316
and electroacupuncture for CINV, 160
which
suggests overall low quality or too few studies. Thus, future
research on the impact of these integrative therapies on the
relevant clinical outcomes is warranted. A limitation to the
generalizability of our findings is that the majority of partic-
ipants in the clinical trials we evaluated were non-Hispanic
white women with high socioeconomic status relative to the
general population. In addition, none of the trials examined
age-related responses and or differential responses in pre-
menopausal versus postmenopausal women. There is a clear
need to design well powered, controlled trials using the best
standard treatment control or an appropriate placebo.
Challenges of Implementing Integrative Therapies in Breast Oncology
Patients with cancer face several psychological and physical
challenges as they move through cancer diagnosis, treat-
ment, and survivorship. According to National Comprehen-
sive Cancer Network guidelines, comprehensive clinical
programs should systematically screen for cancer-related
symptoms and side effects in the process of mandated screening
for distress. This review and others support subsequent referral
or provision of clinical services to include both evidence-based
conventional and integrative therapy options. 194,409
On the basis of recent estimates from the US National
Health Interview Survey, 75% of individuals with a history
of cancer use one or more complementary and integrative
therapies. 410
Many North American cancer centers now
operate formal integrative oncology programs. Because most
of these services are not reimbursable by insurance, the
methods and models of funding and implementing these
programs vary; some programs and services are fully funded
and are provided free of charge to patients, some are entirely
paid for out-of-pocket by patients, and some are a combina-
tion of both. Often, mind-body therapies already are avail-
able from trained clinical staff at cancer centers, such as
oncology nurses or social workers, and hence are more read-
ily accessible at low or no cost. Others, such as massage
therapy and acupuncture, may be covered by some forms of
insurance, varying by country, province/territory, and state.
Implementing complementary and integrative therapies
in a clinical setting requires not only funding and infrastruc-
ture but also well trained, knowledgeable providers. Many
of the integrative therapies do not have a one-size-fits-all
approach and need to be provided and administered by
appropriately trained practitioners who can evaluate which
are the best forms and techniques to use with a specific
patient. Although training and credentialing for many
CA CANCER J CLIN 2017;67:194–232
VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 221
integrative providers varies by jurisdictions, best practices
suggest that providers be trained to the highest standard of
their profession, even if that exceeds the state-based or
province-based standards, such as a requirement for institu-
tional credentialing that may include proctoring. As the
fields of integrative therapies are expanding, there are now
new professional associations that specialize in oncology, for
example, the Society for Oncology Massage and the Oncol-
ogy Association of Naturopathic Physicians.411,412
Future Research
Rigorous clinical research that appropriately reflects integra-
tive care as it is used in the community and at integrative
cancer centers is needed to responsibly move this field for-
ward. Integrative modalities can be tested in addition to
standard supportive treatments, or even in place of them, if
the standard therapy is associated with side effects or signifi-
cant costs and the trial design allows for early discontinua-
tion in the event of futility. Clinical trials designed to test
efficacy in tightly controlled, academic research settings are
often testing protocols that are not realistically implement-
able in the community setting. Implementation and dissem-
ination research designs to consider include pragmatic trials
that involve multimodal therapies applied in the manner in
which they are typically offered in clinical settings. This
approach, while unable to pinpoint clear causal relationships
between specific interventions and outcomes, allows an
exploration and evaluation of clinical impact that is more
truly generalizable. Head-to-head comparisons of different
integrative therapies and conventional symptom-
management therapies would help provide some specificity
and direction for health care providers making recommen-
dations to patients. Comparative-effectiveness research test-
ing integrative modalities in relationship to pharmacological
and other approaches would also be informative in provid-
ing options as well as comparisons of toxicities and cost
effectiveness. Studies that examine mechanism of action are
also needed; however, the emphasis here is on trials of
agents that are actively in use, unlike novel pharmacological
therapies. Importantly, interventions need to be tested in
economically and culturally diverse patient populations to
understand the applicability of an intervention to the grow-
ing population of cancer survivors.
Future studies need to include systematic assessments of
treatment toxicities, including toxicities from both the inte-
grative and the conventional therapies. In this review, when
possible, the NCI CTCAE are used to describe cancer treat-
ment side effects. However, many of the trials did not report
toxicities or adverse events; and, among the trials that did,
the majority did not assess toxicities and adverse events sys-
tematically. The CTCAE are a set of criteria for the standard
grading and classifications of adverse effects of drugs used in
cancer therapy and the US Food and Drug Administration is
increasingly using CTCAE patient-reported outcomes
(CTCAE-PROs) to monitor treatment side effects. 413,414
Ideally, trials will include systematic evaluation of both pro-
vider (ie, CTCAE) and patient (ie, CTCAE-PROs) assess-
ments of adverse events. If future trials do not use these
methods, at minimum, validated measurement tools need to
be used to allow for ongoing quantitative assessments of
adverse events using robust statistical analyses.
Ongoing challenges include the inability to blind partici-
pants to most of the integrative modalities studied, because
most measures are subjective and thus are susceptible to sug-
gestive biases in which patients perceive benefit to an inter-
vention simply because they are receiving it. By using a
mixed-methods model of research, including both qualita-
tive inquiry that explores the patient’s experience of their
treatments and quantitative data, will be helpful to validate
and better justify the use of integrative therapies. In addi-
tion, the use of both subjective and objective patient-
reported outcomes should be used within a mixed-methods
model. This approach can be used in both clinical trials and
in prospective observational studies. To better enable real
clinical uptake and change, knowledge translation experts,
patients with cancer, policy makers, and decision makers
should be involved in both study design and interpretation
to better enable integration of these therapies into clinical
practice.
In conclusion, awareness of the base of evidence for com-
plementary and integrative therapies based on the recently
published SIO guidelines and the emerging literature
should be a core competence for the cancer care provider
and should be applied in decision making for patients with
breast cancer who require supportive care. Billions of dollars
are spent each year on complementary and integrative health
therapies with unknown benefits and on those that have
thus far been shown to be ineffective.410 Research in this
area could save large amounts of health care dollars and
resources and, more importantly, can redirect patients to
treatments with known benefits and better safety profiles.
This article provides greater depth of discussion of these
interventions, such that clinicians and patients can begin the
process of integration based on patient needs in their spe-
cific setting and context. �
Acknowledgements: We thank the following internal and external reviewers for their insightful comments and critiques: Internal reviewers: Executive Com- mittee of the Society for Integrative Oncology; Board of Trustees of the Society for Integrative Oncology; Donald Abrams, MD (University of California at San Francisco), Ting Bao, MD (Memorial Sloan Kettering Cancer Center), Gustav Dobos, MD (Duisberg-Essen University), Petra Klose, MD (Duis- berg-Essen University), Omer Kucuk, MD (Emory University), Jodi MacLeod (University of Pennsylvania), Gregory Plotnikoff, MD (Minnesota Personal- ized Medicine), and Santosh Rao, MD (Banner MD Anderson Cancer Cen- ter). External Society for Integrative Oncology reviewers included Gabriel Hortobagyi, MD (The University of Texas MD Anderson Cancer Center), Shelley Hwang, MD (Duke University), and Anna Wu, PhD (University of Southern California).
Integrative Therapies During and After Breast Cancer Treatment
222 CA: A Cancer Journal for Clinicians
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