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170
K. Borsky and F. Tsang-Wright
lated to HRQOL in breast cancer patients were
excluded. No exclusion was made based on geographic region, interventions, patient or cancer
characteristics.
Outcomes ofInterest
Outcomes of interest were factors inuencing the
quality of life in breast cancer patients and interventions impacting the QOL.In a rst step, the
full text of papers researching the generic question of what factors inuence the HRQOL in
breast cancer patients were reviewed to create a
pool of factors. These factors were then assigned
to 4 categories, identied by the authors upon
reviewing recurring topics in literature. In a second step, the literature researching specic interventions targeting factors identied in step 1 was
reviewed to identify areas that can be targeted in
clinical practice but also to analyse potential mismatches in clinical practice and available evidence to improve the HRQOL of breast cancer
survivors.
Results
Selected Studies
The literature research yielded 65 results, out of
which 17 were excluded according to the above
criteria, and the remaining 48 were included.
Factors Inuencing HRQOL inBreast
Cancer Patients
A total of 6 systematic reviews in the past 10
years searched the literature for factors inuencing the HRQOL in breast cancer patients. 5 studies were restricted by the geographic region they
included, only one analysed the global literature
on this topic. The factors found to inuence
HRQOL in breast cancer patients were grouped
into 4 main themes and are summarized in
Table11.1.
Patient andLesion Characteristics
In the patient and lesion characteristic category,
there was a negative correlation between QOL
and advanced staged cancer (especially metastatic cancer), presence of comorbidities/higher
Charlson comorbidity index, longer time between
diagnosis and treatment, and certain ethnicities
(black worse than white, Malaysians worse than
Chinese or Indians, middle eastern worse than
European/Asian counterpart) [2–9]. Longer time
since diagnosis positively inuences QOL [2, 3].
Across the studies, there is a mixed inuence of
age on quality of life. While some studies report
improved QOL with older age [6], others report
unclear association [2, 3] or no correlation [4].
Treatment
In the treatment category, there are only three
factors with a clear association with QOL.Both
chemotherapy (independent of the used regime)
and active cancer treatment (compared to completed treatment) have a negative impact on
HRQOL [3, 5, 10, 11]. One study identied a
positive inuence of traditional Chinese medication as adjuvant treatment on QOL [2]. Receiving
endocrine therapy was found to have a positive
effect in one study [3] and to have no clear effect
on QOL in another study [2]. All studies evaluating different surgical approaches, radiotherapy or
targeted therapy found no clear association for
either of the three treatment modalities and
HRQOL [2, 3, 12].
Social andPsychological Factors
The social and psychological category have by
far the most factors inuencing the HRQOL, and
most of them have a clear correlation. Low social
support (i.e. living alone), lower educational
level, poorer perceived overall medical care, previous mental health issues (especially anxiety
and depression), and lower self-efcacy in symptom management all have a negative impact on
QOL [2, 3, 6]. Being employed, having children,
support groups (including online), cancer care
programs, self-management programs, problemsolving/coping skills, optimism, spiritual and
religious wellbeing all lead to a higher HRQOL
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Previous mental health struggles Lymphoedema
Low self-efcacy Obesity
Having children
Support groups
Cancer care programs
Optimism
Spiritual wellbeing
Problem-solving skills
171
Endocrine therapy Low income
Targeted therapy Being married
Radiotherapy
Traditional Chinese medication Being employed Exercise
Patient and lesion characteristics Treatment Social and psychological factors Physical factors
Ethnicity Chemotherapy Low social support Pain
Comorbidities Active treatment Low education level Fever
More advanced stage Poor health system Fatigue
↑ Time between diagnosis and treatment
Table 11.1 Factors inuencing HRQOL of breast cancer patients
Age Surgery Unmet needs
↑ Time since diagnosis
Red stands for factors with a negative and green with a positive effect on HRQOL.There are contradictory reports in the literature on the inuence of the orange factors
172
K. Borsky and F. Tsang-Wright
[2–4, 6, 10]. Three factors show contradictory
evidence. One review found unmet needs to have
a negative impact on QOL [3], while another
review agreed with these ndings for all needs
except for unmet sexual needs that showed a positive correlation in some of their included studies
and a negative correlation in the others [2]. The
same holds true for lower-income/nancial difculties that were found to have a negative impact
in two studies [7] and showed contradictory evidence in another review [2]. Lastly, being married had contradictory impacts on QOL in all
studies analysing this factor [2, 6].
Physical Factors
Regarding physical factors inuencing HRQOL
in breast cancer patients, two studies found regular exercise to have a positive impact [2, 3].
Disease or treatment-related physical symptoms,
namely pain, fevers, fatigue, dyspnoea, or lymphoedema, are all associated with lower QOL, and
so is obesity [3].
Intervention Specic Evidence
ofHRQOL
As summarized above, several studies identied
different factors inuencing the HRQOL of
breast cancer patients. However, out of the 48
included systematic reviews, 42 analysed and
compared specic treatments or interventions
and are summarized below. Naturally, none of
them concern the patient or lesions specic
factors.
Treatment
It is unclear if endocrine therapy in general inuences QOL. However, if a patient experiences
symptoms from endocrine therapy, one study
showed that both pharmacological and nonpharmacological interventions to address the
symptoms improve the QOL [13]. Furthermore,
there is no difference in QOL when using
Tamoxifen compared to an aromatase inhibitor
[14], and the addition of targeted therapy to endocrine therapy does not deteriorate HRQOL [15].
A total of 7 studies compared specic types of
surgeries in regard to HRQOL outcomes. One
showed no difference in HRQOL for breast
reconstruction and breast-conserving surgery but
superiority of both methods over mastectomy
[16]. There is also no clear evidence found
between oncoplastic breast-conserving surgery
and breast-conserving surgery alone [17], when
comparing immediate to delayed autologous
abdominal ap reconstruction [18] or when
assessing the effects of additional autologous fat
transfer after implant reconstruction [19]. One
review described superior QOL outcomes of
autologous breast reconstruction compared to
alloplastic reconstruction after mastectomies
[20].
Only one review looked into scalp cooling in
chemotherapy patients to improve QOL and
found no signicant effect in most of the reviewed
studies [21].
There was one review suggesting a positive
inuence of alternative medicine on HRQOL.
4 reviews analysed the effects of specic complementary and alternative medicines (CAM). 3
studies that analysed orally administered CAM
such as herbs and capsules or dietary interventions in the form of a Mediterranean diet found
the results to be inconclusive or to have no effect
[22–24]. 1 study that analysed arts therapy found
no effect on QOL [25].
Social andPsychological Interventions
Support of breast cancer patients, both social and
psychological, was found to have a signicant
impact on HRQOL. This can be challenging in
many ways. Not all patients have an extensive
social support system surrounding them or live in
countries with less developed support networks.
Two reviews researched the inuence of mobile
phone apps and eHealth programs designed to
support cancer management on QOL and found
these interventions to positively affect QOL [26,
27]. 7 studies evaluated specic psychological
interventions to improve QOL.There is good evidence that cognitive behavioural therapy
improves the quality of life in breast cancer
patients [28–31]. Evidence for mindfulnessbased therapy, psychoeducational and psychoso-
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cial support, although less strong, shows similar
trends [30, 32, 33]. Furthermore, specic psycho-
logical interventions targeted at fatigue (which,
as described above, has a negative association
with QOL) showed improved QOL [34].
Physical Interventions
Out of the physical factors that proved to improve
QOL, the literature only provides evidence for
interventions targeting two of them, namely
physical exercise and lymphoedema.
A common side effect of axillary node clearances is lymphoedema of the ipsilateral arm, and
two reviews looked into options to improve
HRQOL in patients suffering from this. Both
complex decongestive therapy and vascularized
lymph node transfers have favourable impacts on
QOL [35, 36].
13 studies research different physical exercises and their outcomes on QOL. 6 out of these
13 specically research the effects of yoga. All 6
studies found a signicant improvement in QOL
of breast cancer patients who practice yoga and
suggest that it is as effective as other forms of
exercise, but none of the studies could show
superiority for yoga over other physical activities
[37–42]. One review analysed the available literature on the effects of Thai Chi on the QOL but
lacked sufcient evidence to come to a conclusion on its effectiveness [43]. The remaining 6
studies looked at non-specic physical activity
interventions. 5 reviews found at least a trend in
improvement in QOL from exercise [44–48] but
the estimated effect size varied greatly amongst
the studies from minimal to clearly signicant.
One review emphasized that the crucial element
to improve QOL is the length of the session [44].
While longer sessions did improve QOL, shorter
did not [44]. 1 review found no effect of exercise
on QOL [49].
Discussion
Patient andLesion Characteristics
The negative association of advanced breast
cancer with HRQOL highlights the importance
of prevention and early detection. Screening
programs, education of the public on selfexamination and prevention, as well as swift
access to primary care providers and specialist
clinics are paramount. Furthermore, there is a
clear need for a holistic approach with the aim
of optimising all existing comorbidities. If these
are neglected due to the focus on the cancer
treatment, this will negatively inuence the
QOL.
Age was the one factor in the patient and
lesion characteristics that had no clear correlation
with QOL.Some studies suggested that younger
age meant more worries regarding childcare
responsibilities, employment, and fear of death
which all negatively inuence QOL.Others argue
that physical symptoms such as pain or the presence of comorbidities in older patients lead to
worse QOL.While this is an interesting discussion, it is of limited clinical relevance as age is a
non-modiable factor and cannot be targeted for
improvement.
Treatment
The one common treatment modality consistently associated with signicantly lower
HRQOL is chemotherapy. While there are apparent survival benets from chemotherapy, this
highlights the need to carefully evaluate the riskbenet prole prior to committing any patient to
chemotherapy. The impacts on QOL should be
discussed with the patients, and they need to be
actively involved in the decision-making
process.
Interestingly, although chemotherapy is the
only treatment that across all studies showed a
clear association of QOL and treatment, only one
review analysed interventions to improve the
QOL of patients undergoing chemo. In contrast,
15 other studies looked into specic surgeries,
endocrine treatment, radiotherapy or CAM, all of
which have no proven inuence on QOL.With a
proportion of close to a third of breast cancer
patients undergoing chemotherapy, this identies
a clear need for further research with a considerable potential to improve patient’s QOL [50].
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K. Borsky and F. Tsang-Wright
Avoiding delays in treatment and minimising
the time patients receive active cancer treatment
is another possibility to improve QOL.Clear targets for treatment completion should be in place
with regular audits to check if these targets are
met and to implement pathway optimisations if
this is not the case.
While there is a lot of debate going on mainly
amongst the surgeons on the ideal surgical treatment modality, there is currently no evidence in
literature favouring one technique over the other
in regard to improving the patient’s quality of
life. Numerous studies have shown that there is
no survival advantage or disadvantage between
the different techniques, and clinicians can therefore be guided by the suitability of the lesion to a
specic technique, the patient’s preferences, and
of course, their personal skill set without compromising the patients future QOL outcome.
Endocrine, radiotherapy and targeted therapy
again show no clear impact on QOL.The addition of these treatments does not seem to directly
translate into a reduction in quality of life, and
these adjuvant treatments can therefore be used
when deemed suitable and safe. If a patient, however, does experience side effects from endocrine
therapy, the literature shows that it is essential to
address them promptly as both nonpharmacological, as well as pharmacological
interventions, improve QOL. Regarding endocrine therapy, there is no difference in QOL
between Tamoxifen and aromatase inhibitors,
and the decision can be based on other criteria. It
is also valuable to note that the combination of
endocrine and targeted therapy does not deteriorate QOL and can therefore be used together
when deemed appropriate. One study identied
traditional Chinese medication to have a positive
impact on QOL. This study was based on an
Asian population and, therefore, susceptible to
population bias. There is no literature researching
this on a non-Asian population, and therefore, no
recommendations can be made for clinicians
practicing outside of Asia. This is further highlighted by the fact that all reviews analysing other
CAM interventions could not show any signicant effect on QOL.
Social andPsychological Factors
The factors identied in this category are of great
interest for two reasons. Firstly, out of all the
available literature, they are the largest group to
inuence HRQOL, with most of them having
clear negative or positive correlations. Secondly,
the vast majority are highly modiable and therefore ideal to be targeted to optimise QOL in
breast cancer patients. Technical advances and
global connectivity through the internet allow for
signicant improvements in the social support of
breast cancer patients. This is further emphasized
by the literature backing the effectiveness of
mobile apps and eHealth portals aimed to
improve patient’s cancer management and, therefore, their quality of life. App-based support
groups proved to be efcient in other cancers and
allow to include patients from geographical
regions with less social support or that have fewer
support systems in place. Self-management, coping skills, developing an optimistic outlook, and
dealing with mental health issues such as depression or anxiety can all be supported by the respective professionals through cognitive behavioural
or psychotherapy. While psychological support is
often accessible to cancer patients, this, of course,
varies from country to country, and psychological support is still surrounded by stigmata, especially in certain cultures. The evidence in the
literature on the effectiveness of psychological
intervention suggest that these should be much
more integrated and normalised in cancer care
and extend beyond passive supporting session
into active therapy sessions such as cognitive
behavioural therapy.
Being married showed contradictory evidence
across different reviews. It was hypothesized that
while being married increases social support,
physical impairments caused by the cancer and
treatments such as changed body image and sexual dysfunction can strain the relationship and
add stress for the patient.
One study found contradictory evidence
related to nancial income. This particular study
evaluated an Asian population, and in some Asian
countries, patients in lower-income classes qual-
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ify for health care benets while higher-income
classes have to pay larger amounts out of pocket.
There is a clear population bias in this specic
nding, and all other studies evaluating countries
without such benet schemes found higher
incomes to have a positive effect on HRQOL,
a global scale. Lastly, there is a controversy
around unmet needs and their inuence on
QOL. While all studies agreed that all other
unmet needs negatively inuence QOL, this does
not always seem to be the case for sexual needs.
Intuitively one would presume that unmet sexual
needs have a negative impact on QOL, but it is
hypothesized that a high sex drive and, consequently, unmet needs can indicate positive body
image and fewer physical side effects, which is
indicative of a patient group with overall higher
QOL.
Physical Factors
There are several physical factors identied in
the literature that inuence HRQOL in breast
cancer patients. Like the social and psychological
factors, these are of great clinical interest as they
can easily be targeted by specic interventions.
Lymphoedema is a well-recognised complication
of the treatment of breast cancer. The indications
for axillary clearance should be carefully evaluated, and if patients do suffer from this complication, both surgical and non-surgical therapies
have shown to improve QOL and need to be
addressed with the patient promptly.
There is a noteworthy focus of the currently
available literature on exercised-based interventions to improve QOL, mainly on the effects of
yoga. While exercise independently was found to
have a signicant impact, it is also hypothesized
that it mediates positive effects through reducing
fatigue and body weight or obesity, which all in
themselves are proven to have a negative effect
on QOL. There is no exercise strategy with
proven superiority over other physical activity.
Only one study suggested that exercise does not
inuence QOL.It has to be noted that this study
only looked at improvements of QOL through
exercise in patients currently receiving radiotherapy, and the ndings of this review can therefore
not be generalised. Overall, the evidence on exercise is of very mixed quality with a signicant
number of low-quality publications and a lack of
high-quality papers. Interestingly, the time of
sessions seems to be of signicance, with times
below a certain threshold showing no effect.
Most reviews included papers with very different
exercise regimes, and the majority did not comment on session length. This heterogeneity in
included studies might explain the differences in
reported effect size to some degree.
Although the effects are of mixed size, there is
no generalisable paper that did not at the very
least describe a positive trend in QOL when exercise is added as an intervention. This stands in
contrast to current clinical practice, where the
focus on physical activity is minimal. Breast cancer patients are often instructed on specic exercises post-surgery and have leaets handed out to
them. Structured exercise programs for breast
cancer patients are not common practice but do
offer an exciting potential to improve
HRQOL. One can imagine group lessons as a
cost-effective measure to create social support
and provide structured workout regimes as part
of a holistic cancer care approach.
Limitations
Most included reviews had a subset of similar
limitations with further limitations specic to the
research questions and used methodology.
Most systematic reviews struggled with the
differences in reporting HRQOL of their included
studies ranging from simple patient reports such
as bad, medium, good to robustly tested and evaluated tools such as the EORTC-QLQ-BR23 or
the FACT-B. This makes comparing or pooling
results and estimating effect sizes very challenging and, in some cases, even impossible.
Furthermore, there is no homogeneity in using
either global QOL assessments or breast-specic
tools. Some studies found no effect of particular
interventions on global QOL but signicant differences in the breast subscales. However, not all
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K. Borsky and F. Tsang-Wright
studies assess breast-specic subscales and might
have missed signicant effects. This methodological heterogeneity might explain the contradictory ndings when trying to identify factors
inuencing QOL.This issue was addressed in a
recent systematic review by Ghislain etal. 2016.
They concluded that while overall, the reporting
on HRQOL in breast cancer patients has
improved, with the advent of new treatments,
there is a need for adjusted HRQOL tools to
improve the quality of HRQOL reporting. They
also note the frequent absence of robust HRQOL
research hypotheses and the emphasis on statistical results over clinical signicance [51].
Next, while there were some longitudinal
study designs, most of the studies included in the
systematic review were retrospective crosssectional studies relying on the patient’s recall of
how they felt at certain times during their cancer
journey. This can lead to arbitrary associations of
symptoms and treatments or interventions. Most
studies also have a high risk of selection bias,
with only a couple of reviews focusing on randomized controlled trials and the rest of them
including mainly non-randomized trials.
Adding to the selection bias, there is an unfortunate geographical bias, especially in the studies
analysing factors that can inuence QOL.Only 1
systematic review in the past 10years assessed
factors inuencing HRQOL on a global patient
cohort. All other reviews reported ndings for
specic geographical regions with signicant
cultural, social, economic, and physical differences. This greatly interferes with attempts to
compare the results or draw a conclusion on a
global scale.
Future Research andClinical
Practice
This comprehensive literature research has identied several exciting areas for future research.
There seems to be a highly selective focus of the
current literature on certain factors hypothesised
to inuence QOL but lacking evidence-based
backing. This is probably most pronounced in the
treatment category. While there is no clear evi-
dence for surgery or any adjuvant therapy other
than chemotherapy signicantly inuencing the
QOL, there are numerous studies comparing
QOL related outcomes of different surgeries with
a relevant proportion of systematic reviews in the
past 10years focusing either on surgery or endocrine therapy. There is only 1 review researching
interventions to improve QOL in patients undergoing chemotherapy even though evidence on its
association with QOL is most robust in this
group. This should be one focus of future
research.
There is also strong evidence for the inuence
of social support and cancer management strategies on QOL and very limited research on
improving social support through eHealth.
eHealth is becoming more and more popular in
various elds of medicine and the few available
studies suggest promising results when integrating eHealth into cancer care. If proven to be
effective, this could change clinical practice and
should be investigated by future research.
Lastly, there are several surprising factors that
show contradictory evidence in the literature
regarding their impact on QOL. These include
for example, age, most adjuvant treatments, and
certain social factors. It can be argued that the
conicting evidence might be due to the limitations mentioned above and it would be interesting to investigate this with future research that
addresses the methodological concerns raised
above.
This summary of the available literature has
also shown good evidence for psychological
interventions and incorporating exercise regimes
to improve QOL, both of which fall relatively
short in current clinical practice. These could be
two areas to target in the future.
Conclusion
With breast cancer being the most common cancer globally and ongoing advances in treatment
leading to prolonged survival, it is of great interest to research HRQOL in these patients and
identify areas that can be targeted for improvement. Several factors inuencing HRQOL in
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breast cancer patients could be identied when
reviewing the available literature on this topic.
Clear positive associations were found for time
since diagnosis, problem-solving skills, cancer
care programs, support groups, having children,
optimism, spiritual wellbeing, and exercise.
Negatively associated are advanced stages,
comorbidities, long time between diagnosis and
treatment, specic ethnicities, chemotherapy,
being in active treatment, low social support, low
level of education, poor health care systems, previous mental health history, low self-efcacy,
physical symptoms such as pain, fever, fatigue,
lymphoedema and being obese. There is currently conicting evidence for age, different surgical techniques, endocrine therapy, targeted
therapy, radiotherapy, unmet needs, low income,
and being married. Regarding interventions targeting these discussed factors, the current literature is mixed. In the factors related to treatment,
there is a focus on factors with contradictory evidence regarding their inuence on QOL, such as
surgery and endocrine therapy, while neglecting
interventions targeting factors that have a known
association to QOL.In other categories such as
psychological and physical factors, there is a
good literature body evaluating interventions
suggesting promising results for psychological
interventions such as cognitive behavioural therapies or the implementation of exercise regimes.
One of the most signicant limitations of the
available literature is the mixed quality of
research with a relevant amount of low to moderate quality research and only very few highquality papers. The methodological limitations of
past research should be addressed in the future to
overall improve the quality of HRQOL reporting
in breast cancer patients.
Summary Points
• Factors inuencing the quality of life in breast
cancer patients can be grouped into the 4 main
categories: patient and lesion characteristics,
treatment, social and psychological factors,
and physical factors
• For patient and lesion characteristics, only a
few factors are modiable. Clinicians should
focus on early detection and swift diagnosis/
treatment to improve quality of life.
• In the treatment category, only chemotherapy
and ongoing cancer treatment have a clear
negative effect on quality of life. Indications
for chemotherapy should be carefully evaluated and future research on how to reduce the
negative impact of chemotherapy on quality of
life is needed.
• For social and psychological factors, there is
good evidence that social and psychological
support improves quality of life. As highly
modiable factors, these should be much more
integrated into a holistic approach to cancer
care.
• There is good evidence that physical activity
improved quality of life directly as well as
indirectly by addressing negatively associated
factors such as fatigue and obesity.
• Lymphoedema has a very high morbidity and
indications for axillary dissection should be
made carefully and patients offered both conservative and surgical interventions to minimise its impact.
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