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PERCEPTIONS AND PREVALENCE OF EXERCISES
AMONG BREAST CANCER SURVIVORS AT
ONCOLOGY HOSPITAL, HO CHI MINH CITY

研研研研Mai Thi Minh Nguyet.
研研研研研Shiow – Li Hwang

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PERCEPTIONS AND PREVALENCE OF EXERCISES
AMONG BREAST CANCER SURVIVORS AT
ONCOLOGY HOSPITAL, HO CHI MINH CITY

Graduate student: Mai Thi Minh Nguyet
Supervisor& Committee:
Professor: Shiow- Li Hwang

Meiho University
Graduate Institute of Health care
Thesis
A thesis submitted to the Graduate Institute of Health Care of
Meiho University
In partial fulfillment of the requirement for the degree of

Master of Health Care

July 2014


Abstract
Background: Breast cancer is the most common cancer among women both in the
developed and developing countries with an estimation of 521,817 deaths in 2012
worldwide. Scientific evidence showed that physical activity could have physiological
and psychological benefits toward breast cancer survivors. In Vietnam, breast cancer is
also the most common cancer among women across the country. An existing problem
in breast cancer management in Vietnam is that a large amount of breast cancer cases
are lately diagnosed and the rate of late diagnosis is up to 49.5% that predispose to
difficulty in treatment regimens and reduced effectiveness of breast cancer treatment.
Another concern comes from the fact that survivors after breast surgery do not receive
adequate health cares, especially those related to physical activity, to prevent the
recurrence of breast cancer.
Objective: The aim of the study was to describe perceptions on physical activity and
the prevalence of exercise performance after surgery among breast cancer survivors.
Methods: The study was a cross-sectional study carried out in Oncology Hospital, Ho
Chi Minh city from January to February 2014. The Health Belief Model was applied
in the study to investigate the perceptions of patients. The exercise performances of
patients were recorded through three interval time after surgery including the first
seven days, first 6 weeks and beyond 6 weeks. The significance of the results was
assessed by ANOVA test, t-test and Chi-Square test at p-value of 0.05 using SPSS
version 16.

Results: There were a total of 121 patients enrolled in the study. The mean age of all
breast cancer survivors was 52.75 ± 10.60. Most of patients had the level of education
was secondary school or over. The mean family income of participants was 4.15 ±
3.71 (1-20).
In general, the proportion of patients perceived toward suggestion of performing

exercises and barriers of performing exercises were not high. Other perception
including perceptions of possibility of recurrence of breast cancer, perceptions of
severity of breast cancer, perceptions of social support reached at average level, while
perception of the benefits of performing exercises gained high level. The results
showed that in three different phases after surgery, exercise performance among
3


patients was surprising high. In the first seven days, the rate of performing exercises
was 86.78%. In the same token, the rates in the 6 weeks and beyond six weeks were
considerable high (94.21% and 82.64%, respectively).
Age, education, and marital status had showed significant associations with
exercises performance at the first 6 weeks. In addition, perceptions of benefits of
exercises performance and the prevalence of exercises performance beyond 6 weeks
had a statistical significance (p=0.03). .
Conclusion: Most of aspects in the perceptive model had low percentage of patients
being aware of, except perceptions of benefits of exercise performance. Patients had
high prevalence of performing exercises; however, types of recommended exercises
and sports were not abundant and patients did not receive the instructions from healthcare workers, especially in the prolonged stage after surgery. The data also showed
that perception of benefits of exercise performance had a strong relationship with the
prevalence of exercising; therefore education or training on benefits of physical
activity on preventing breast cancer was supposed to have positive impacts on
prevalence of doing physical activity among breast cancer survivors.
Key words: breast cancer, exercise, perceptions

4


Acknowledgements
This thesis was carried out at Nguyen Tat Thanh University and Meiho

University under the guidance of my supervisor, Dr Shiow-li Hwang, and Dr. TsueyHuang. I would like to express my deep gratitude to my supervisor and other
professors who had spent their precious time to instruct and facilitate me complete this
thesis. I would like to send my thanks to all authors of published works cited in the
thesis for providing valuable resources and related knowledge during my studying.
I would like to give my special thanks to the Director Board, Science Council,
Ethical Council, doctors and nurses of the Oncology Hospital for their endless
supports in helping me fufill the thesis. My thanks also gave to officers of the
International and Postgraduate Training Department of Nguyen Tat Thanh University,
scientists from the Meiho University, and my classmates who had provided
administrative supports and encouragement during my studying.
There is no success without supports, more or less or directly or indirectly, from
others individuals. From the beginning to the end of my studying, I had received lots
of concerns and supports from my best friends and colleagues. With the gratefulness
from bottom of my heart, I would like to thank Mr. Lam, Dr. Cang, Dr. Cu and health
care staff of Oncology Department and Nursing Deparment of 30/4 Hospital. I never
foget what my best friends (Minh, Mai, Xuan and Nga) had done to me during hard
working days for data collection. I would like to be grateful to participants in the study
who although suffered physical and mental pains as well as numerous concerns in
daily life had spent their valuable time to provide important information those will be
used to help other patients receive better health care. All of those made a strong
motivation to me in completion of the study.
Finally, my deep gratitude was sent to my beloved husband and two sons, my
close friends and colleagues who always encourage, concern and share many aspects
of life to me and those made myself more confident to finish my thesis.

5


List of tables
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List of figure
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6


Contents
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Chapter 1. Introduction
1.1. Statement of this research
Breast cancer is the most common cancer among women both in the developed
and developing countries (Ferlay et al., 2012). It is estimated that worldwide 521,817
women died in 2012 due to breast cancer (Ferlay et al., 2012). Incidence rates vary
greatly worldwide from 27 per 100,000 in Middle Africa and Eastern Asia to 96 in
Western Europe. In most of developing regions the incidence rates are below 40 per
100,000 (Ferlay et al., 2012). The lowest incidence rates are found in most African
countries but here breast cancer incidence rates are also increasing. Breast cancer
survival rates are also reported with a wide range from ≥ 80% in North America,
Sweden and Japan to around 60% in middle-income countries and below 40% in lowincome countries (Coleman, 2008).
Physical activity is an important contributor to health and the related outcome of
quality of life (Farrell, Braun, & Barlow, 2002). One health condition that appears to
benefit from a physically active lifestyle is cancer. Both physical and psychological
benefits are associated with physical activity for cancer survivors. Indeed, multiple
studies during the past 20 years, coming from North America, Europe, Asia, and
Australia, have demonstrated that physical activity contribute to decrease the risk of

breast cancer among female populations. A 2008 review reported that physical activity
was associated with a 25 to 30% decrease in risk of developing breast cancer
(Friedenreich & Cust, 2008), while a systematic review reported a 15 to 20%
reduction in risk of breast cancer with higher physical activity, and a risk reduction of
about 6% per hour of physical activity per week (Monninkhof et al., 2007). The results
from the Nurses’ Health Study cohort and the Health, Eating, Activity and Lifestyle
Study showed that women who are physically active after a breast cancer diagnosis
are at lower risk of a recurrence and death caused by breast cancer (Holmes, Chen,
Feskanich, & et al, 2005). In addition, physical activity play an important role in
reducing fatigue, breast cancer-related lymphoedema, physical ability and healthrelated of life of breast cancer survivors (Headley, Ownby, & John, 2004; Johansson,
Tibe, & Weibull, 2005; Mutrie, Campbell, & Whyte, 2007; Turner, Hayes, & Reul8


Hirche, 2004).
In Vietnam, breast cancer is also the most common cancer among women across
the country. In 2012, there were approximately 11,067 new cases of breast cancer and
the incidence rate was 23 per 100,000 women. The number of deaths due to breast
cancer was 4,671 cases and the mortality rate was 9.9 per 100,000 women (Ferlay et
al., 2012). A 2012 report showed that Ha Noi and Ho Chi Minh are two cities in which
breast cancer prevalence are highest. Namely, the breast cancer prevalence in Ha Noi
is approximately 30 per 100,000 women and in Ho Chi Minh city is 20 per 100,000
women (bachmaihospital, 2012). A review of Oncology Hospital, Ho Chi Minh
showed that breast cancer was accounted for 17.7% of all cases of cancer among
women in the period of 1998-1999; however, it increased up to 19.7% between 2003
and 2004 (Nguyen, Le, Pham, & Dang, 2008).
An existing problem in breast cancer management in Vietnam is that a large
amount of breast cancer cases are lately diagnosed and the rate of late diagnosis is up
to 49.5% that predispose to difficulty in treatment regimens and reduced effectiveness
of breast cancer treatment. Another concern comes from the fact that survivors after
breast surgery do not receive adequate health cares, especially those related to physical

activity, to prevent the recurrence of breast cancer. Indeed, there are lack of
consultations for survivors about how to and to what extent the exercises are done
during three to seven days after surgery. Consequently breast cancer survivors do not
recognize the importance of physical activity and they are reluctant to practice
recommended exercises. As they are discharged, there are not any instructions on how
to perform physical activities at home provided and health facilities where survivors
are treated do not follow up their performance of physical activities as well.

1.2. Significance of this research
The Oncology Hospital in Ho Chi Minh city is one of the largest hospitals in the
country that serves as the main cancer center for treatment of patients from the
southern of Vietnam. It is estimated that 5,243 patients who have hospital admission
for treatment of all kinds of cancer at the hospital each year; of these there are 15%
women who have suffered and be treated breast cancer.
After breast surgery, patients are participated in a physiotherapy program in
9


which health care workers instruct patients to perform proper breathing and physical
activities. These activities are very important for patients to prevent atelectasis,
pneumonia, scar contracture and improve the quality of life of patients as well. For the
first 3 to 7 days after surgery, patients should follow a designed program including
essential exercises such as deep breathing, moderate movement of affected arm, and
cool-down exercises. For six weeks after surgery, patients continue performing the
recommended exercises at home and begin to practice jogging for 20 to 30 minutes
each day. After four months, patients are asked to revisit the hospital for check-up
health condition and receive more consultations on physical activities.
The program has been established and applied for many years but the
effectiveness has not been evaluated yet. In fact, during the first week after surgery,
the performance of recommended exercises of patients could not be assessed because

of unknown reasons. Moreover, not all patients were instructed and received
consultations on physical activity due to the fact that health care workers could not
take care of all patients. There are not any surveys or studies conducted to investigate
what patients have learnt from the program and what they thought about the exercises
(unlike or frustrated towards the exercises). Finally patients do not report their
performance of exercises at home so the evaluation of effectiveness of the program is
impossible. To get the answers for all of these questions, a study therefore is
necessary.

1.3. The aim of this research
The aim of the present study was to describe perceptions of patients on physical
activity after breast surgery and prevalence of exercises performance. The following
research objectives address the overall aim of this study.
1. To describe the perceptions of physical activity among breast cancer survivors.
2. To describe prevalence of exercise performance among breast cancer survivors.
3. To identify the association between perceptions and other potential factors and
performance of exercises among breast cancer survivors.

1.4. Chapter summary
Breast cancer is one of the most frequent cancers among women with the average
10


number of death approximately 521,817 worldwide. The incidence rates of breast
cancer in different regions vary greatly with a higher trend in developed countries and
lower trend in developing countries. On the contrast survival rates of breast cancer in
high-income nations have been increasing due to the fact that patients received better
care, while theses figures appear to be lower in low- and middle-income nations.
Physical activity is one of the most effective way to prevent the recurrence of breast
cancer thank to its mental and physical effects. Numerous studies have demonstrated

that physical activity can reduce the risk of acquiring breast cancer, incidence and
mortality of breast cancer and improve quality of life of survivors.
The number of Vietnamese women who have breast cancer is estimated
approximately 11,067 cases in 2012, yielding 23 cases per 100,000 women. Of new
cases, there are 4,671 women died from breast cancer, so the mortality rate is about
9.9 cases per 100,000 women. A problem exists in breast cancer management is that
women often have late diagnosis of breast cancer because they can not recognize signs
and symptoms of the disease. Moreover, lack of consultations about physical activity
and insufficient physical practices after breast surgery make the risk of recurrence of
breast cancer in these patients higher.
Oncology Hospital at Ho Chi Minh city each year receives approximately of
5,243 cases with all types of cancer including breast cancer (accounting for 15% of
total cases). There is a physiotherapy program for survivors after breast surgery
established for years, but its effectiveness to date is still in question. The physical
activity of survivors after first 6 weeks of surgery and later could not be tracked;
moreover, their perceptions of exercises that have a significant impact on exercises
performance are not known. Therefore, the present study focuses on evaluation of
perceptions of exercises among survivors after breast surgery, their prevalence of
exercises and the association between perceptions and exercise performance.

11


Chapter 2. Literature Review
2.1. Introduction
This chapter is a review of studies involving in the topic of the study. The
epidemiology of breast cancer including statistics on incidence, mortality, survival rate
and related factors those could affect the risk of developing breast cancer is described
at first. Secondly, evidence of the impacts of physical activity toward breast cancer
prevention will be the best explanation for the suggestion of performing exercises to

prevent breast cancer. A variety of impact mechanisms of physical activity that have
been well documented are included in the third part of the chapter. The fourth part
introduces recommendations of international guidelines toward physical activity for
survivors after breast cancer. Finally a wide range of studies are discussed to illustrate
the prevalence of and related factors affecting to physical performance of survivors
globally.

2.2. Epidemiology of breast cancer
2.2.1. The burden of breast cancer worldwide
Breast cancer is the second most common cancer in the world and, by far, the
most frequent cancer among women with an estimated 1.67 million new cancer cases
diagnosed in 2012 (25% of all cancers) (Ferlay et al., 2012). It is believed that breast
cancer occurs more frequently in developed countries than in developing countries
with incidence rates ranging from 27 per 100,000 in Middle Africa and Eastern Asia to
96 in Western Europe (Ferlay et al., 2012).
Breast cancer ranks as the fifth cause of death from cancer overall (522,000
deaths) and while it is the most frequent cause of cancer death in women in less
developed regions (324,000 deaths, 14.3% of total), it is now the second cause of
cancer death in more developed regions (198,000 deaths, 15.4%) after lung cancer
(Ferlay et al., 2012). The range in mortality rates between world regions is less than
that for incidence because of the more favourable survival of breast cancer in (highincidence) developed regions, with rates ranging from 6 per 100,000 in Eastern Asia to
20 per 100,000 in Western Africa (Ferlay et al., 2012).
12


2.2.2. Risks factors of breast cancer
Demographical factors
Age may be the strongest risk factors relating to breast cancer. Women with
advancing age will have a higher risk of developing breast cancer compared to
younger women (Ferlay et al., 2012).

Socio-economical factors
Women who have higher social class have a higher risk of acquiring breast
cancer (Kreiger, 1990). Studies have also showed that women living in developed
countries and have a high living standard have a higher risk of developing breast
cancer. The reason is that they have fewer children on average and shorter interval of
breastfeeding (Collaborative Group on Hormonal Factors in Breast Cancer, 2002).
Reproductive factors
Women who have early age of menarche have higher risk of breast cancer
(Tanner, 1973). However, late menopause also increases the risk of breast cancer with
average of 3% increase risk when the age advances one year (Collaborative Group on
Hormonal Factors in Breast Cancer, 1997). Women who had children reduced the risk
of breast cancer approximately 30% when compared to women never having children.
And women who have two issues will have reduced 15% risk compared to one issue
women (Ewertz et al., 1990). Breastfeeding may be the protective factor to breast
cancer but it is not certain. However, the fact that breast never lactated is more prone
to cancer than a lactated breast (Thai & Nguyen, 2009; Tworoger, Eliassen, Sluss, &
Hankinson, 2007).
Potentially modifiable risk factors include weight gain after age 18, being
overweight or obese (for postmenopausal breast cancer), use of menopausal hormone
therapy (combined estrogen and progestin), physical inactivity, and alcohol
consumption. Medical findings that predict higher risk include high breast tissue
density (a mammographic measure of the amount of glandular tissue relative to fatty
tissue), high bone mineral density (women with low density are at increased risk for
osteoporosis), and biopsy-confirmed hyperplasia (overgrowth of cells), especially
atypical hyperplasia (overgrowth of abnormal cells). High-dose radiation to the chest
for cancer treatment also increases risk.
Risk is also increased by a family history of breast cancer, particularly having
one or more first-degree relatives with breast cancer (though most women with breast
13

cancer do not have a family history of the disease). Inherited mutations in breast
cancer susceptibility genes account for approximately 5%-10% of all female breast
cancers and an estimated 4%-40% of all male breast cancers, but are very rare in the
general population (much less than 1%). Most of these mutations are located in
BRCA1 and BRCA2 genes, although mutations in other known genes have also been
identified. Individuals with a strong family history of breast and certain other cancers,
such as ovarian and colon cancer, should consider counselling to determine if genetic
testing is appropriate. Prevention measures may be possible for individuals with breast
cancer susceptibility mutations. In BRCA1 and BRCA2 mutation carriers, studies
suggest that prophylactic removal of the ovaries and/or breasts decreases the risk of
breast cancer considerably, though not all women who choose this surgery would have
developed breast cancer. Women who consider prophylactic surgery should undergo
counselling before reaching a decision.
There is limited, but accumulating evidence that long-term, heavy smoking
increases the risk of breast cancer, particularly among women who began smoking at
an early age. The International Agency for Research on Cancer has concluded that
there is limited evidence that shift work, particularly at night, is also associated with
an increased risk of breast cancer.
Modifiable factors that are associated with a lower risk of breast cancer include
breastfeeding (Lacey, 2009), moderate or vigorous physical activity, and maintaining a
healthy body weight (Danaei, 2005). Two medications including tamoxifen and
raloxifene have been approved to reduce breast cancer risk in women at high risk.
Raloxifene appears to have a lower risk of certain side effects, such as uterine cancer
and blood clots; however, it is only approved for use in postmenopausal women.

2.3. The impacts of physical activity toward breast cancer prevention
The study on association between physical activity and breast cancer might begin
from two studies of Rose Frisch and Leslie Bernstein. Rose Frish was the first scientist
that developed the physical activity–breast cancer hypothesis in the early 1980s. In her

study published in 1985, she noted that the prevalence of breast cancer in the nonathletes was about twice that of the college athletes (Odds ratio = 1.86 [95% CI: 1.003.47]). The next major advance in the physical activity–breast cancer hypothesis was
made by Leslie Bernstein. Her study in 1994 examining the role of lifelong exercise
14


participation and breast cancer risk in young women (< 40 yrs) was a landmark study
that ignited research on the role of physical activity and breast cancer in particular, and
physical activity and cancer in general. The results showed a strong inverse
relationship between levels of lifetime exercise and estimated that women who
exercised for 3.8 hour/week or more had about a 60% reduction in risk for breast
cancer compared to women who reported no exercise participation (Odds ratio = 0.42
[95% CI: 0.27-0.64]). One year after the study of Leslie, Rohan et al (1995) examined
the association between physical activity and breast cancer survival by conducting a
prospective population-based study of 412 womenIn this study physical activity was
assessed before diagnosis and the association could not be found significantly.
Consequently, later studies focused on studying the association after diagnosis.
From the time of these innovative reports were published, many epidemiologic
studies and clinical trials have investigated the physical activity and breast cancer
hypothesis and the accumulated evidence was sufficiently compelling that there is
strong evidence that physical activity may prevent breast cancer.
2.3.1. Physical activity and risk of breast cancer
In 2,987 Nurses' Health Study (NHS) participants with 280 breast cancer deaths
and 8 years median follow-up, women who exercised the equivalent of 3 to 5 hours
per week of walking had half the risk of dying of breast cancer (relative risk = 0.50,
95% CI 0.38 to 0.84), with no evidence for increased benefit for greater exercise
(Holmes et al., 2005). A systematic review reported a 15 to 20% reduction in risk of
breast cancer with higher physical activity, and a risk reduction of about 6% per hour
of physical activity per week (Monninkhof et al., 2007). A 2008 review reported that
physical activity was associated with a 25 to 30% decrease in risk across 62 studies
with 83% of the positive studies reporting a dose-response relationship (Friedenreich

& Cust, 2008).
2.3.2. Physical activity and mortality/survival/recurrence of breast cancer
There was also a reduced risk of breast cancer recurrence and total mortality, and
the benefit of physical activity was particularly apparent among women with
hormone-responsive tumours (Holmes et al., 2005). The Collaborative Women's
15


Longevity Study (CWLS) of 4,482 women with breast cancer followed for 6 years
with 109 deaths reported a comparable decreased risk of breast cancer death and total
death (Holick et al., 2008). The Health, Eating, Activity and Lifestyle (HEAL) study
in 933 women reported a greater reduction in mortality for physical activity after
diagnosis (67%) compared to physical activity measured before diagnosis (31%), and
a 45% decreased risk of death for women who increased their physical activity after
diagnosis (Irwin, Smith, McTiernan, & et al, 2008). The Women’s Healthy Eating and
Living (WHEL) Study found that only when combined with higher fruit and vegetable
intakes was exercise at 2 years post-diagnosis associated with favourable survival
(Piercel et al., 2007). A small study of 603 breast cancer patients in Canada showed no
association of breast cancer survival with exercise shortly after surgery (Borugian et
al., 2004).
2.3.3. Physical activity and fatigue
Fatigue or cancer-related fatigue (CRF) usually begins in the second or third
week of treatment and may continue to increase for the duration of the therapy (Perun,
2004). This type of fatigue has consistently been reported by cancer patients as the
most common and distressing symptom experienced during treatment, affecting 25%
to 93% of patients (Lawrence, Kupelnick, & Miller, 2004).
Exercise interventions implemented with cancer patients during active treatment
have reported positive effects on subjective levels of fatigue. Among women being
treated for breast cancer, studies utilising home-based exercise programs have reported
decreases in fatigue of between five and twenty percent post-intervention. In

comparison, increased levels of fatigue (between 20 and 40%) have been reported
among the usual care controls (Mock, Pickett, & Ropka, 2001; Schwartz, 2000). A
recent trial involving 108 women spanning the duration of their adjuvant therapy for
breast cancer, found women who adhered to a walking program reported significantly
lower levels of fatigue (20% on average) compared to women who did not comply.
The levels of fatigue for the non-compliers post-intervention more than doubled and
were in the moderate range compared to the mild or absent range for women who
adhered to the walking program (Mock, Frangakis, & Davidson, 2005). Decreases in
levels of subjective fatigue post-intervention have also been reported among mixed
16


groups of cancer survivors in home-based (Courneya, Friedenreich, & Sela, 2003) and
group-exercise programs (Adamsen, Quist, & Midtgaard, 2006). In addition, similar
findings have been found among advanced breast cancer patients for whom seated
exercise mitigated the effect of fatigue over the course of treatment (Headley et al.,
2004).
Exercise interventions conducted post-treatment have obtained similar positive
results to those conducted during treatment. In a trial involving breast cancer survivors
14 months post-treatment, stationary cycling three times per week over 15 weeks
significantly decreased levels of fatigue by over 50% in comparison to the 18%
decrease observed in the control group (Courneya, Mackey, & Bell, 2003). Similar
trends have also been reported in supervised aerobic interventions conducted 11
months post-treatment (Rogers, Shah, & Dunnington, 2005), and in mixed-type
exercise programs carried out at 17 months post-diagnosis (Turner et al., 2004).
Cardiovascular problems and the presence of depressive symptoms were
identified in one study as the two main correlates of long-term fatigue among breast
cancer survivors (Bower, Ganz, & Desmond, 2006). Research has demonstrated that
both depression (Brosse, Sheets, & Lett, 2002) and cardiovascular problems (Briffa,
Maiorana, & Sheerin, 2006) can be positively influenced by regular physical activity.

Physical activity interventions early after treatment therefore have the potential to not
only reduce fatigue, but to positively impact on these co-morbid conditions in the
longer term.
2.3.4. Physical activity and breast cancer-related lymphoedema
Breast cancer-related lymphoedema (BCRL) has been described as one of the
most distressing and unpleasant sequelae following surgery (Fialka-Moser, Crevenna,
& Korpan, 2003). A 2001 review reported the prevalence of BCRL (across treatments
and time since treatments) to be approximately one in four women, with an overall
prevalence of 26%, increasing over time (Erickson, Pearson, & Ganz, 2001).
As with fatigue, health professionals once cautioned breast cancer survivors to
avoid participation in vigorous, upper-body exercise for fear of causing or aggravating
lymphoedema. However, recent studies carried out with breast cancer survivors
17


demonstrated that exercise did not exacerbate or lead to the development of BCRL. In
fact, two studies involving women with pre-existing BCRL reported a tendency
toward decreases in the volume of the affected arm (Johansson et al., 2005; Turner et
al., 2004).
2.3.5. Physical activity and physical capability or fitness
A person’s fitness, also known as aerobic fitness, is measured objectively by
maximal oxygen uptake (USDHHS, 1996). This refers to the body’s ability to deliver
oxygen to working muscles. Most recently, two trials of eight- and 12-week
supervised exercise interventions with breast cancer patients reported effect estimates
for improvement in aerobic capacity of close to 1.0 and 0.7, respectively, at the end of
the intervention compared to usual care controls (Daley, Crank, & Saxton, 2007;
Mutrie et al., 2007). Along with aerobic capacity, exercise interventions that
incorporated resistance training have shown improvements in other aspects of physical
fitness including strength (Adamsen et al., 2006; Kolden, Strauman, & Ward, 2002)
and flexibility (Courneya, Friedenreich, et al., 2003; Kolden et al., 2002).

2.3.6. Physical activity and weigh gain
Weight gain has consistently been reported by women undergoing adjuvant
chemotherapy. A review looking at this issue reported that significant weight gains
occurred in 50% to 96% of all patients with early-stage breast cancer who were
receiving adjuvant chemotherapy (Demark-Wahnefried, Rimer, & Winer, 1997).
Weight gains between two and six kilograms appear to be most common (Lankester,
Phillips, & Lawton, 2002), although much larger gains are not unusual (DemarkWahnefried et al., 1997).
Regular physical activity has been the strongest predictor of weight stability
among breast cancer survivors (Demark-Wahnefried, Peterson, & Winer, 2001).
Evidence from exercise interventions also supports this notion. Participants assigned
to exercise either reduced or maintained their weight, while the weight of women in
control groups increased (Schwartz, 2000). A similar positive outcome using the sum
of skin folds measure was observed among a group of mixed-cancer survivors at the
completion of a 10-week therapy program. The skin fold measure was significantly
18


reduced among participants assigned to group therapy and exercise, while the skin
fold measure significantly increased among participants assigned to group therapy
alone (Courneya, Friedenreich, et al., 2003). Similar results have also been reported
among survivors 14 months post-treatment (Courneya, Mackey, et al., 2003). While
the majority of these studies have utilised aerobic exercise, the incorporation of
strength training directed towards the leg region may result in even greater benefits
(Demark-Wahnefried et al., 2001).
2.3.7. Physical activity and health-related quality of life
Participation in exercise during active cancer treatment has been shown to
positively impact on a patient’s overall health-related quality of life (HRQoL) and
well-being. Two recent trials (both involving a 12-week exercise program with women
undergoing adjuvant therapy for breast cancer) described clinically important changes
in HRQoL between baseline and follow-up compared to usual care controls. Women

who were assigned to the exercise group reported a mean change in HRQoL of
approximately 12 points at 12 weeks (Campbell, Mutrie, & White, 2005), while the
second study reported an improvement of six points at six months follow-up (Mutrie
et al., 2007). A similar trend has been described for women with advanced-stage
disease. A seated exercise intervention reportedly minimised the decline in global
HRQoL during chemotherapy for women diagnosed with stage IV breast cancer
compared to controls (Headley et al., 2004).

2.4. The mechanism of physical activity affecting to breast cancer
Many studies have demonstrated that several physiological factors could affect
the risk of developing, recurrence and mortality of breast cancer. These factors,
directly or indirectly, are in turn affected by physical activities of patients.
2.4.1. Physiological factors of breast cancer
Immune function
The immune system is thought to play a role in protecting against breast cancer
by recognizing and eliminating abnormal cells.
19


Mammographic density
Strong evidence exists that the characteristics of breast tissue as seen on a
mammogram, measured as mammographic density, provide information about breast
cancer risk. Women with high levels of mammographic density have a fourfold to
sixfold greater risk of developing breast cancer than women with lower levels of
mammographic density; thus, mammographic density is a stronger predictor of breast
cancer risk than most traditional risk factors. Mammographic density reflects
proliferation of the breast epithelium and stroma, in response to growth factors
induced by current and past circulating sex hormone levels. Mammographic density
may vary throughout lifetime, with the pattern reflecting the accumulated breast
cancer risk at the time the mammogram was obtained. Factors that change

mammographic density may also change breast cancer risk.
Sex hormones
Estrogen, a female sex hormones with mitogenic and proliferative influences, is
strongly associated with the development of breast cancer (EHBCCG, 2002 ;
McTiernan, 2006). A pooled analysis of nine cohort studies showed that the risk for
breast cancer in postmenopausal women increased significantly with increasing
concentrations of estradiol, free estradiol, and estrone (EHBCCG, 2002 ). Other
findings from epidemiological studies further support the etiologic role of estrogen in
breast cancer, showing that breast cancer risk is associated with early menarche, late
menopause, low parity, and use of exogenous estrogens, all of which are linked to
prolonged or extensive exposure of breast tissue to estrogen stimulation (EHBCCG,
2002 ; McTiernan, 2006).
Androgens, such as testosterone, also may play a role in breast cancer. Elevated
testosterone levels were associated with increased risk for primary and secondary
breast cancer risk in both premenopausal and postmenopausal women (Calle,
Rodriguez, & Walker-Thurmond, 2003; Irwin, McTiernan, & Baumgartner, 2005).
Body fat

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Body fat, or weight control, may also play an important role in mechanism of
developing breast cancer (Irwin et al., 2005; Irwin, Yasui, & Ulrich, 2003; McTiernan,
2006). Women who gain weight after breast cancer diagnosis are at increased risk for
breast cancer recurrence and death as compared to women who maintain their weight
after diagnosis (Goodwin et al., 2002; Irwin et al., 2005; Neilson, Friedenreich, &
Brockton, 2009). Analyses from a recent study showed that weight gain after diagnosis
(~5 to 10 lbs) was related to approximately 50% higher rates of breast cancer
recurrence and death (Kroenke, Chen, & Rosner, 2005).
The influence of obesity on breast cancer risk varies by menopausal status:

obesity has a protective effect against breast cancer in premenopausal women but is
associated with increased risk in postmenopausal women (Goodwin & Pritchard,
2010; Helzlsouer & Couzi, 1995). The biologic rationale for this difference in effect of
obesity on breast cancer risk is based on the source of endogenous estrogen before and
after menopause (McTiernan, 2006). Although menopausal status may modify the
effect of obesity on breast cancer risk, recent studies have shown a positive association
between weight gain during premenopausal or postmenopausal years and breast cancer
risk (Eliassen & Hankinson, 2008; McTiernan, 2006; McTiernan et al., 2003).
Epidemiological studies have also shown that premenopausal and postmenopausal
women who are overweight or obese when they are diagnosed with breast cancer are
more likely to experience a recurrence or die of breast cancer than women who are of
a normal weight (McTiernan, 2006). Furthermore, some, but not all, studies suggest
that women who gain weight after breast cancer diagnosis, regardless of menopausal
status, are at increased risk for breast cancer recurrence and death as compared with
women who maintain their weight after diagnosis (McTiernan, 2006). This is
especially worrisome given the fact that most women who are treated for breast cancer
gain a significant amount of weight in the year after breast cancer diagnosis, and
return to pre-diagnosis weight rarely occurs (Irwin et al., 2005).
Insulin and Insulinlike Growth Factors (IGF).
Insulin, insulin-like growth factor-1 (IGF-I) and IGF-binding proteins (IGFBP)
are believed to be important mechanisms associated with the development of breast
cancer. In a study of women with early-stage breast cancer, higher insulin levels were
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associated with a two and three times higher risk of recurrence or breast cancer death,
respectively (Goodwin et al., 2002). Another study also confirmed that IGF-I have a
major role in promoting breast cancer (McTiernan, 2006). The explanation is that
insulin and IGF-1 can enhance tumor development by stimulating cells to multiply and
inhibiting cells from dying, or undergoing programmed cell death (i.e., apoptosis)

(Gray, Stenfeldt-Mathiasen, & De Meyts, 2003; Kaaks & Lukanova, 2001; Yu &
Rohan, 2000).
IGFBPs are important determinants of the bioavailability of IGF-1, and IGFBP-3
is an important carrier of IGF-1 in circulation. IGFBP-3 also may either stimulate or
suppress cells from multiplying by restricting the availability and biological activity of
IGF-I (Gray et al., 2003; Yu & Rohan, 2000). Although the data are not consistent,
high levels of IGF-I and low levels of IGFBP-3 have been associated with an
increased risk of breast cancer and adverse prognostic factors after a diagnosis of
breast cancer (Calle et al., 2003; Hankinson et al., 1998; Morimoto, White, & Chen,
2002).
Adipocytokines.
Adiponectin, a hormone produced by adipocytes (fat cells) is involved in
metabolism and inflammation (Fantuzzi, 2005; Kumada, Kihara, & Ouchi, 2004;
Wolf, Wolf, & Rumpold, 2004). Adiponectin has a strong inverse correlation with fat
mass (Arita, Kihara, & Ouchi, 1999); under conditions of obesity, adiponectin
concentrations are reduced (Vona-Davis, 2007). For this reason, adiponectin is gaining
recognition as an interesting and strongly predictive indicator of abdominal fat.
Among postmenopausal women, an inverse relationship between circulating
adiponectin levels and breast cancer risk has been observed (Miyoshi, Funahashi, &
Kihara, 2003).
Biomarkers of low-grade chronic inflammation, such as C-reactive protein
(CRP), serum amyloid A (SAA), tumor necrosis factor-α (TNF-α), and interleukin
(IL)-6, have been linked with increased cancer risk (Il’yasova, Colbert, & Harris,
2005). Although there is limited epidemiologic literature on inflammation and breast
cancer risk (Neilson et al., 2009), these biomarkers of inflammation may affect breast
cancer through their effects on apoptosis, cell proliferation, angiogenesis, and
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metastasis (DeNardo & Coussens, 2007). Chronic inflammation has also been

associated with higher rates of recurrence and death for several cancers including
breast cancer (Ardizzoia & Brivio, 1992; Monninkhof et al., 2007). Breast cancer
patients have been shown to have elevated concentrations of CRP prior to surgery, and
CRP is higher in women with more advanced stage of disease (McMillan, Sattar,
Angerson, Johnstone, & McArdle, 2001).
Oxidative Stress/DNA repair.
Reactive oxygen species (i.e., free radicals) can play a significant role in breast
cancer via their ability to produce DNA damage as well as damage to other cellular
components which interact with DNA (McTiernan, 2006).
2.4.2. Evidence for impacts of physical activity to risk factors of breast cancer
Physical activityand immune function.
A growing literature of small exercise intervention studies shows that physical
activity improves immune function, both functionally and numerically (McTiernan,
2006). Physical activity appears to enhance proliferation of lymphocytes, increases the
number of natural killer cells and increases lymphokine-activated killer cells activity.
Therefore, physical activity has a protective affect to breast cancer.
Physical activity and mammographic density.
Physical activity may influence mammographic density by favourably changing
certain hormones associated with mammographic density and breast cancer risk. Both
mammographic dense area and percent density have been found to be inversely related
to physical activity in obese postmenopausal women (McTiernan, 2006; Pierce,
Faerber, & Wright, 2002).
Physical activity and sex hormones.
Changes in sex hormones are perhaps the most consistently cited potential
mechanism for the association between physical activity and breast cancer. Girls who
participate in athletics tend to have a later age of menarche and a delay in establishing
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normal ovarian cyclicity. Later age of menarche and slowed establishment of cycling

would decrease the total steroid hormone exposure to the breast (McTiernan, 2006). In
adult premenopausal women, exercise has been associated with decreased levels of
circulating estrogen and progesterone, shortened luteal phase, increased frequency of
anovulation, and an increased incidence of oligomenorrhea and amenorrhea. In
postmenopausal women, physical activity has been found to be associated with
decreased serum estrogens and androgens (McTiernan, 2006; McTiernan et al., 2004).
Increased physical activity also has been associated with increased sex hormonebinding globulin resulting in lower amounts of free active sex hormones in circulation
(EHBCCG, 2002 ; McTiernan et al., 2004).
The primary mechanism of physical activity influencing sex hormones in
postmenopausal women is via decreased body fat, a substrate for estrogen, and
testosterone production, which results in less tissue capable of aromatization of the
adrenal androgens to estrogens. Only one randomized controlled exercise trial has
been published examining the effect of exercise on sex hormone concentrations
(McTiernan et al., 2004). The authors examined the influence of a 12-month exercise
program in postmenopausal women on these hormonal factors and found that exercise
decreased serum estrogens and androgens, and increased SHBG resulting in lower
amounts of free, active estrogens and androgens. Women who lost more body fat with
exercise were noted to have larger changes.
Physical activity and body fat.
Few trials have examined the effect of exercise on outcomes of body composition
in breast cancer survivors. McTiernan (2006) demonstrated that obese individuals
generally exhibit a lower level of habitual physical activity than the non-obese, and
physically active individuals may be less likely to become obese.(McTiernan, 2006) In
a recent publication, moderate-intensity aerobic exercise, such as brisk walking,
performed for approximately 120 min/wk, was associated with modest, yet favourable,
changes in body fat in postmenopausal breast cancer survivors (Irwin, AlvarezReeves, & Cadmus, 2009).
Physical activity and insulin and IGF.
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Few trials that have assessed the effect of exercise on IGFs have had variable
results. Irwin and colleagues (2009) showed that moderate-intensity aerobic exercise,
such as brisk walking, performed on average for 120 min/wk over six months was
associated with a 25% decrease in insulin and 7% decrease in IGF-1 among exercisers,
and a 5% increase in insulin and 2% increase in IGF-1 among controls (21). Given
that high insulin levels promote the synthesis and activity of IGF-I via increases in
insulin-mediated changes in IGFBP-3 concentrations, decreases in insulin would be
predicted to favourably influence IGF levels.
Physical activity and adipocytokines.
Few trials have examined the effects of physical activity on adiponectin in breast
cancer survivors. Recently, Irwin and colleagues (2008) examined the effect of six
months of moderate-intensity aerobic exercise versus usual care on leptin and
adiponectin levels in 75 breast cancer survivors. Baseline correlations between leptin,
adiponectin, and measures of adiposity were strong and consistent with available
literature; however the intervention did not result in statistically significant differences
in levels of leptin or adiponectin between exercisers and usual care participants.
There is evidence that physical activity might reduce chronic inflammation alone,
or by reducing body weight or composition (McTiernan, 2008), given that
inflammatory factors have been shown to correlate with body fat (Vona-Davis, 2007).
However, little is currently known about the effect of physical activity on CRP, IL-6,
and TNF-α in breast cancer survivors.
Physical activity and DNA repair.
Acute exercise may promote free radical production, whereas chronic exercise
improves free radical defences by up-regulating both the activities of key free radical
scavenger enzymes and levels of antioxidants. To date, there are few studies that have
examined reactive oxygen species-related damage or relevant antioxidant enzymes in
the context of exercise in a cancer model.

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