Physical activity among breast cancer survivors. Sheree Harrison. Bachelor of Science (Psychology) Hons (The University of Newcastle)

Transcription

1 Physical activity among breast cancer survivors Sheree Harrison Bachelor of Science (Psychology) Hons (The University of Newcastle) A thesis submitted for the degree of Master of Applied Science (Research) School of Public Health and Institute of Health and Biomedical Innovation Queensland University of Technology February, 2008 i

2 Key Words breast cancer, physical activity, exercise, recovery, health-related quality of life, longitudinal data, public health ii

3 Abstract In Australia, women with breast cancer comprise one of the largest groups of cancer survivors. As a consequence of this, and improved survival rates, the interest in programs to enhance the recovery of cancer survivors is growing. Exercise during and after treatment has been identified as a potential strategy to assist women throughout their treatment and positively influence the recovery and health-related quality of life (HRQoL) of breast cancer survivors. Through the use of an existing data source, this study investigated physical activity rates, explored the factors associated with low levels of physical activity participation, and assessed the relationship between levels of activity and HRQoL among women diagnosed with breast cancer. The population-based sample, obtained in 2002 was comprised of 287 women newly diagnosed with breast cancer, residing in South-East Queensland. Women were followed-up (via subjective questionnaire and objective physical testing) every three months over a 12-month period, from six months post-diagnosis. Physical activity was assessed using the Behavioural Risk Factor Surveillance System (BRFSS) while HRQoL was assessed using the Functional Assessment of Cancer Therapy for breast cancer (FACTB+4). Based on National Physical Activity Guidelines, women were categorised as being sufficiently active, insufficiently active or sedentary at each of the five testing phases (specifically at 6-, 9-, 12-, 15- and 18- months post-diagnosis). Rates of participation in physical activity were relatively stable over the testing period. At 18 months post-diagnosis, 44%, 43% and 13% of women, respectively, were categorised as being sufficiently active, insufficiently active or sedentary. The sedentary or insufficiently active women were more likely to be older, obese or overweight, lack private health insurance, and have received both chemotherapy and radiotherapy, compared with sufficiently active women. Sedentary women consistently reported a lower HRQoL compared to active women (sufficiently or insufficiently active) over the 12-month testing period. This was especially apparent amongst the group of younger women (aged less than 50 years at diagnosis) (p=0.02). This work is among the first to explore physical activity rates specifically among Australian breast cancer survivors, and highlights the potential importance of participating in physical activity to optimise HRQoL during recovery from breast cancer. Specific attention to promote physical activity to the identified group of sedentary and insufficiently active survivors is of particular importance. iii

4 Table of Contents Key Words...ii Abstract...iii Table of Contents...iv List of Tables...vi List of Figures...viii List of Abbreviations...ix Statement of Original Authorship and Contribution...x Acknowledgements...xi Chapter 1: Introduction...1 Chapter 2: Literature Review Overview Breast cancer treatment Physical activity as an intervention Prevalence of physical activity among women with breast cancer Physical activity trends post-diagnosis Methodological issues Summation...26 Chapter 3: Methods Research design Sample and recruitment Data collection Data measurement Data quality and management Statistical considerations Data analysis Ethics approval...47 Chapter 4: Results Physical Activity Participation Participant characteristics Objective 1: Levels of physical activity Objective 2: Comparison with the general population...56 iv

5 4.5 Objective 3: Factors associated with physical activity participation Chapter 5: Results Fitness and HRQoL Objective 4: Objective fitness score comparison Objective 5: The relationship between physical activity and HRQoL Chapter 6: Discussion Overview Synthesis of the findings Limitations of the study Strengths of the study Public health significance and implications for practice and policy Future directions Conclusion References Appendix A Study questionnaire Appendix B Pathology abstraction form Appendix C Comparison of physical activity calculation methods Appendix D Backward stepwise nominal regression model v

6 List of Tables Table 3.1 Three-minute step test (fitness score) look-up table for women, based on heart rate (beats per minute) and age (years)...35 Table 4.1: Demographic and clinical characteristics of participants compared with the target sample of women diagnosed with breast cancer in Table 4.2: Demographic and clinical characteristics of participants compared with the non-participant sample of women diagnosed with breast cancer in Table 4.3: The personal, demographic and lifestyle characteristics of the 287 participants at baseline, six months post-diagnosis...50 Table 4.4: Minutes of weekly physical activity by type reported over the 12- month study period for all women (n=287)...52 Table 4.5: The median time (minutes) and proportions of younger and older women participating in each type of physical activity over the 12-month study period...54 Table 4.6: The proportion of women meeting the physical activity guidelines over the study period Table 4.7: Level of physical activity at 18 months post-diagnosis compared to data from the Queensland female general population Table 4.8: Personal and demographic characteristics of the study sample by level of physical activity at 18 months post breast cancer diagnosis a Table 4.9: Treatment characteristics of the study sample by level of physical activity at 18 months post breast cancer diagnosis a Table 4.10: Behavioural characteristics of the study sample by level of physical activity at 18 months post breast cancer diagnosis a Table 4.11: Health-related quality of life (FACTB+4 subscales) characteristics of the study sample by level of physical activity at 18 months post breast cancer diagnosis a Table 4.12: Other health-related characteristics of the study sample by level of physical activity at 18 months post breast cancer diagnosis a Table 4.13: Breast cancer related complications in the study sample by level of physical activity at 18 months post breast cancer diagnosis a vi

7 Table 4.14: Co-morbidities diagnosed by 12 months in the study sample by level of physical activity at 18 months post breast cancer diagnosis a Table 4.15: Multivariable relationships between demographic, treatment and health-related factors and level of physical activity at 18 months post-diagnosis (n=272) Table 5.1: The age-adjusted changes in mean fitness score a over the five study phases from 6 to 18 months post-diagnosis Table 5.2: The age-adjusted relationship between mean fitness score a and level of physical activity over the 12 month study period (n=182) Table 5.3: The age-adjusted relationship between mean fitness score a and level of physical activity stratified by test phase from 6 to 18 months postdiagnosis b Table 5.4: The age adjusted mean HRQoL (FACTB+4) a of women diagnosed with breast cancer from 6- to 18-months post-diagnosis b (n=287) Table 5.5: Multivariable relationships between demographic, treatment and health-related factors and level of physical activity at 18 months post-diagnosis (n=272) vii

8 List of Figures Figure 3.1: Study recruitment and participation flow chart...31 Figure 5.1: The age-adjusted relationship between mean change in fitness score and change in physical activity (30 minutes or more) from 6 months (time 1) to 18 months post-diagnosis (time 5)...75 Figure 5.2: The age-adjusted mean HRQoL (FACTB+4) over time from 6 to 18 months post-diagnosis for (A.) Younger women (< 50 years) and (B.) Older women (50+ years) diagnosed with breast cancer (n=287)...78 Figure 5.3: The relationship between level of physical activity and HRQoL (FACTB+4) for younger and older women Figure 5.4: The relationship between level of physical activity and HRQoL (FACTB+4) for younger and older women, adjusted for baseline fitness...80 Figure 5.5: (A.) The relationship between level of physical activity and physical well-being for younger and older women, adjusted for age and upper-body function (DASH). (B.) Also adjusted for baseline fitness Figure 5.6: (A.) The relationship between level of physical activity and functional well-being for younger and older women, adjusted for age and upper-body function (DASH). (B.) Also adjusted for baseline fitness Figure 5.7: (A.) The relationship between level of physical activity and social well-being for younger and older women, adjusted for age and upper-body function (DASH). (B.) Also adjusted for baseline fitness...84 Figure 5.8: (A.) The relationship between level of physical activity and emotional well-being for younger and older women, adjusted for age and upper-body function (DASH). (B.) Also adjusted for baseline fitness Figure 5.9: (A.) The relationship between level of physical activity and breast-cancer well-being for younger and older women, adjusted for age, upper-body function (DASH) and arm swelling. (B.) Also adjusted for baseline fitness...87 viii

9 List of Abbreviations ACSM ANOVA BCRL BMI BRFSS CDC CI CLE CRF DASH FACTB FACTB+4 FACTG GLM HRQoL OR PTS QCR QLD QUT RCT SD SPSS UK USA American College of Sports Medicine Analysis of variance Breast cancer-related lymphoedema Body mass index Behavioral Risk Factor Surveillance System Centres for Disease Control Confidence interval Complete local excision Cancer-related fatigue Disabilities of the Arm, Shoulder and Hand Functional Assessment of Cancer Therapy Breast Cancer Functional Assessment of Cancer Therapy Breast Cancer plus Arm Morbidity Functional Assessment of Cancer Therapy General General linear model Health-related quality of life Odds ratio Pulling Through Study Queensland Cancer Registry Queensland Queensland University of Technology Randomised controlled trial Standard deviation Statistical Package for the Social Sciences United Kingdom United States of America ix

10 Statement of Original Authorship and Contribution The work contained in this thesis has not been previously submitted to meet requirements for an award at this, or any other, higher education institution. To the best of my knowledge and belief, the thesis contains no material previously published or written by another person except where due erence is made. As a Research Officer, I was involved in the recruitment, data collection and data entry aspects of the Pulling Through Study project. As a Masters Student, I formulated the aims and objectives specific to this thesis, undertook a comprehensive literature review of topics under the broader area of physical activity following breast cancer, performed all the statistical analyses, presentation of results and subsequent writing of the thesis. Signature.. Date.. x

11 Acknowledgements Foremost, I would like to thank my principal supervisor Beth Newman for firstly giving me the opportunity to be a student again and the opportunity to learn more throughout this degree than I have in all the preceding years of working in research. I am very grateful for all your knowledge, wisdom and constructive advice that has helped me develop as a researcher. To my Associate Supervisor, Sandi Hayes, I would like to thank you for all you encouragement, support and feedback that you provided, no matter where you were in the country. Thank you for reminding me that this isn t just a Masters! and I look forward to continuing to work with you for some years to come. To my work colleagues and friends Tracey Di Sipio and Loretta McKinnon, thank you for sharing this journey with me. Your support, advice and friendship have been instrumental in helping to make this process a very enjoyable one. To all the girls in A113, both past and present, you help make coming into work each day more fun. Thank you to my family who were always interested in what I was doing and how things were going. An extra special thank you goes to my soon to be husband Michael Rye. You encouraged me all the way, especially towards the end so I could finally wrap this thesis up! Thank you for your love and support, you have listened and helped me all along the way and saw me through many technical crises! Thank you for making me laugh everyday. xi

12 Chapter 1: Introduction Breast cancer remains the most common type of invasive cancer among Australian women. In 2002, a total of 12,027 women were diagnosed with breast cancer across Australia. The risk of a first diagnosis before the age of 85 has increased from one in 12 in 1983 to one in eight in However, with continually improving treatment and earlier detection, survival rates also continue to improve. Between and there was a significant increase in relative survival after diagnosis. One-year relative survival increased from 93.2% to 96.7% and five-year relative survival increased from 70.9% to 86.6%. Ten-year relative survival increased from 57.5% for women diagnosed in to 73.6% for women diagnosed in These statistics highlight the high number of women currently living with breast cancer in Australia. In 2002 it was estimated that there were 114,000 women alive who had been diagnosed with breast cancer in the previous 20 years [1]. Although the causes of breast cancer still remain relatively uncertain, a number of factors that contribute to the risk of developing this disease have been identified. Female sex and increasing age are two of the strongest risk factors for breast cancer, while a family history of the disease increases a woman s risk by two to three times depending on the number and degree of relatedness of the affected family members [2]. However, the increased rate of breast cancer in more-well developed countries, and the fact that cancer rates among migrants and their offspring approach the rates of their adopted countries rather than their country of origin, suggest that environmental and lifestyle factors also contribute to breast cancer risk [2, 3]. Nulliparity, older age at menopause and current or recent use of oral contraceptives are each associated with an increased risk and represent some of the most established risk factors for breast cancer [2, 3]. Other lifestyle factors include increased alcohol consumption and larger body mass index, particularly among post-menopausal women. Inverse associations are recognised for breastfeeding, and most notably for this thesis, an active lifestyle. Meta-analyses and reviews have placed this reduced relative breast cancer risk with physical activity somewhere between 20-40% and indicate the presence of a dose-response relationship showing greater reductions in risk with increasing levels of activity [4]. 1

13 With this emerging consensus regarding the inverse association between physical activity and breast cancer risk, it follows that physical activity could also benefit in the recovery process of cancer. As women with breast cancer make up one of the largest groups of cancer survivors, interest in survivorship research and potential interventions to enhance their recovery is imperative. Increasingly, physical activity is a popular choice to focus on as it is a modifiable, lifestyle factor amenable to change. As well as aiding in breast cancer recovery, physical activity has the potential to benefit other diseases, co-morbidities and a person s general health and well-being due to the many and varied effects that exercise has on the human body. The musculoskeletal, endocrine, cardiovascular, immune and neurological systems of the body are all benefited to some degree when a person participates in exercise. As a consequence, physical activity offers a more holistic approach to positively aid in the cancer recovery process [5]. The basis for this approach stems from the health benefits derived from physical activity seen in the general population and other disease populations [6]. However, the idea that physical activity can positively benefit the health of a population is not new. Our ancestors up to the beginning of the industrial revolution incorporated strenuous physical activity as a normal part of their daily lives. It was enjoyed, not only as a necessity for gathering food, shelter and safety, but as an integral component of life [6]. Throughout Western history, the close connection between exercise and medicine dates back to earlier than 400 B.C. As quoted in the Surgeon General s Report on physical activity, the Greek physician Hippocrates at this time wrote [6] : Eating alone will not keep a man well; he must also take exercise. For food and exercise, while possessing opposite qualities, yet work together to produce health. For it is the nature of exercise to use up material, but of food and drink to make good deficiencies. And it is necessary, as it appears, to discern the power of various exercises, both natural exercises and artificial, to know which of them tends to increase flesh and which to lessen it; and not only this, but also to proportion exercise to bulk of food, to the constitution of the patient, to the age of the individual, to the season of the year, to the changes in the winds, to the situation of the region in which the patient resides, and to the constitution of the year. 2

14 This classical notion that individuals can improve their health through their own actions proved to be a dominant influence on medical theory as it developed over the centuries. In more recent times, several consistent findings have emerged from the epidemiologic research regarding the protective health effects attained by being physically active. Physical activity has been demonstrated to reduce the risk of coronary heart disease (CHD), hypertension, non-insulin dependent diabetes mellitus, osteoporosis, obesity and anxiety, depression and improve quality of life [6]. Other studies have also described the association between sedentary behaviour and increased levels of all-cause mortality rates [6]. The conclusions of these studies have been supported by experimental studies showing that exercise training improves CHD risk factors and other health-related factors, including blood lipid profile, resting blood pressure, body composition, insulin sensitivity, bone density, immune and psychological function [7]. With regards to cancer, the most consistent findings to date relate to patients with colon cancer, where regular physical activity has been shown to decrease the risk of occurrence [6]. While the findings are more inconsistent for other types of cancer, an increased amount of attention has focused on the effects of physical activity during the recovery process. A framework has been proposed to examine physical activity across the cancer experience identifying six points after diagnosis whereby physical activity could impact on the cancer outcome. These six points include the buffering prior to treatment, coping during treatment, rehabilitation immediately after treatment, health promotion and survival for those with positive treatment outcomes and palliation for those without positive treatment outcomes [8]. So far research has examined the effects of physical activity among cancer survivors, throughout this framework and despite some methodological limitations and small sample sizes, the existing evidence suggests that exercise is not only safe and feasible during cancer treatment, but is also essential to aid in the recovery process and improve fitness [9]. While much of this research has been conducted with breast cancer survivors, information relating to levels of participation in physical activity within this group, particularly in Australia, is lacking. There is a need to investigate physical activity participation by breast cancer survivors in Australia and to explore what effect this has on quality of life and 3

15 recovery. Understanding the characteristics that both influence and inhibit participation in physical activity will help future interventions and programs target appropriate groups of women and potentially influence the standard care of breast cancer survivors. This work involves addressing these issues by accessing and analysing data from an existing data source, collected as part of the Pulling Through Study (PTS). The PTS was a population-based, longitudinal study designed to track the physical and psycho-social recovery of women diagnosed with breast cancer in South-East Queensland. Specifically, the primary outcomes involved the assessment of healthrelated quality of life (HRQoL) and upper-body functioning. Physical activity was not intended as a primary outcome, but was assessed as a behavioural characteristic that may influence the primary outcomes of interest. Physical activity was comprehensively assessed and as such the collected data provided a unique opportunity to contribute to an area lacking in empirical evidence, particularly in the Australian setting. Women were followed-up every three months over a 12-month period, beginning six months after their diagnosis. The focus of this study was the course of recovery over the medium term. Theore, baseline was measured at six months post-diagnosis as by this time, many of the short-term, treatment-related side effects would have dissipated. The study consisted of two components. The first involved objective measures of fitness and upper-body functioning, while the second involved a selfreported survey to gather information on treatment, behaviours and psycho-social aspects of their recovery. The aim of these analyses was to describe the level and patterns of physical activity among women recently diagnosed with breast cancer. The following research objectives address the overall aim of this study: 1. To describe the levels and patterns of physical activity reported by women diagnosed with breast cancer, living in South-East Queensland, over a 12-month period from 6 to 18 months post-diagnosis. 4

16 2. To compare levels of physical activity among Australian breast cancer survivors with levels in the general population. 3. To describe the influence of demographic, social, and treatment characteristics on levels of physical activity at 18 months post-diagnosis. 4. To compare subjective reports of physical activity to an objective measure of physical fitness. 5. To investigate the impact physical activity has on HRQoL over time. This thesis begins with the literature review, which describes the treatment associated with breast cancer, the potential treatment-related side-effects and complications experienced by breast cancer survivors and the role exercise may play during and following breast cancer treatment. The prevalence of exercise undertaken by breast cancer survivors, as reported in the available literature is also discussed. Chapter 3 describes the aims, objectives and methods used to initially gather the dataset. The statistical analyses employed to address each study objective are also discussed in detail. The results have been separated into two chapters. Chapter 4 addresses level of physical activity, the rates of participation within the sample of PTS breast cancer survivors and the factors associated with participation. Chapter 5 describes two outcomes, fitness and HRQoL, and the relationship between these and physical activity. Finally, Chapter 6 provides a discussion bringing together the major findings of the results chapters and acknowledges the study s strengths and limitations. The chapter concludes with a summary of the implications for public health and makes further recommendations for future research and breast cancer care. 5

17 Chapter 2: Literature Review 2.1 Overview The emergence of exercise during and after treatment as a strategy to assist cancer patients holds positive benefits for both the physical and psychological aspects of recovery. This is a dynamic area of research with a growing body of scientific literature available on the subject. As women with breast cancer make up one of the largest groups of cancer survivors, this in turn has been lected in this area of research. The scientific literature was reviewed via extensive searches of health-related databases including: Medline, Current Contents, CINAHL, Health Reference Centre Academic, Meditext, and ScienceDirect. Searches were not limited by publication date. This was supplemented by the manual search of erence lists from published papers. Search terms used to identify relevant citations included: breast cancer, physical activity, exercise, quality of life, rehabilitation, complications, side-effects and recovery. Searches were also conducted using names of key authors in the field. Much of the available literature is from studies conducted in the United States of America (USA), Canada and the United Kingdom (UK). This was supplemented with Australian material where available. This review begins by describing the current treatment available for women diagnosed with breast cancer and the side-effects and complications that can result from this treatment. Support for the use of physical activity to aid in the recovery process (in the form of randomised controlled trials and interventions) is then discussed. Next, the existing literature describing the prevalence of physical activity among women diagnosed with breast cancer is examined and some key methodological issues involved in the assessment of this population are identified. 2.2 Breast cancer treatment The surgical treatment of breast cancer usually involves one of two basic procedures, a complete local excision (CLE), also erred to as breast-conserving surgery, or a total mastectomy. Breast-conserving surgery is appropriate for women whose 6

18 tumours are uni-focal and where clear margins can be achieved, and will typically be followed by adjuvant radiation therapy. A total mastectomy includes the complete excision of breast parenchyma, preserving the underlying pectoral muscles. This option is generally appropriate for women whose tumours extend widely within the breast or have ill-defined margins that defy breast-conserving surgery. Both procedures are typically carried out in combination with sentinel node biopsy and/or axillary lymph node dissection [10]. The aims of treatment to the axilla are to eradicate metastatic disease, provide an assessment of nodal status for evaluation of prognosis and to determine the form of adjuvant therapy. Dissection and irradiation are both used in the treatment of the axilla to reduce rates of axillary recurrence. Randomised controlled trials (RCTs) have established that CLE and total mastectomy (both with axillary dissection) are equally effective in terms of local recurrence and survival [10]. Surgical techniques used in the treatment of breast cancer can lead to both acute and late side-effects or complications, which have the ability to influence a woman s physical and psychological recovery. Acute, short-term effects typically occur during the course of treatment and normally resolve within a few months of completion. In comparison, late or long-term effects will usually occur after treatment has completed and may have prolonged impacts lasting for many years. Complications following surgery include post-surgical wound infections, haematomas, seromas, and upper-arm, breast or chest-wall pain [10]. Pain has been a frequently described sideeffect, with one report suggesting 21% of breast cancer survivors still experience some form of pain four years post-surgery [11]. Impairments of physical functioning are also common and include reduced range of motion in the shoulder, reduced grip and upper-body strength, and increases in arm volume (lymphoedema) [12]. Radiotherapy is commonly used after CLE to reduce the risk of local recurrence and the need for further surgery, while with mastectomy it is used in patients at high risk for local chest wall or regional lymph node recurrence [10]. The average duration of radiation treatment spans five to six weeks, and depending on the protocol, radiotherapy can also incur both acute and late side-effects. The most common acute side-effects include skin reactions, pulmonary symptoms such as shortness of breath 7

19 (dyspnoea), cough and pain in the breast, chest wall or axilla [13, 14]. Lymphoedema and fatigue also can occur as acute or late side-effects. Chemotherapy or adjuvant systemic treatment (i.e. drugs) may be administered prior to surgery to reduce the size of a tumour, or more commonly, after surgery in combination with radiotherapy to treat any remaining cancer and reduce the chance of recurrence [10]. Acute side-effects frequently associated with chemotherapy include nausea, vomiting, diarrhoea, alopecia, fatigue, and neutropenia. Sleep disturbances, depression, difficulty in concentrating and anxiety have all been frequently reported by women undergoing radiation and/or chemotherapy. Many of the symptoms persist throughout treatment and in the months following treatment completion [13, 15]. Longer-term side-effects and complications include weight gain, infertility, cardiac dysfunction, and possible cognitive impairments [16]. 2.3 Physical activity as an intervention Numerous interventions, programs and support groups are available to cancer patients to assist in their recovery and to decrease the impact of these side-effects and complications. For example, within Australia, the Cancer Councils within each state offer face to face support groups and telephone help lines. However, these interventions are mainly psychosocial and are not likely to deal with the physical and functional problems experienced by cancer patients. Interventions involving exercise or physical activity have the capacity to positively affect recovery both physically and psychologically, due to the many and varied effects that exercise can have on the human body. The musculoskeletal, endocrine, cardiovascular, immune and neurological systems of the body are all influenced to some degree when a person participates in exercise [5]. As a consequence, physical activity offers a holistic approach, encompassing not only the physical and emotional recovery from cancer, but with far-reaching effects on a person s general health and well-being. Research in this area is beginning to dispel early clinical concerns about prescribing exercise to cancer patients, with numerous reviews and controlled trials being conducted [17, 18]. Randomised controlled trials (RCT) of exercise interventions with cancer patients have assessed the impact of physical activity using numerous indicators of recovery, physical functioning and well-being. Key outcomes from the 8

20 current literature including fatigue, lymphoedema, physical ability, weight gain, and HRQoL are discussed in turn 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 [14]. It is defined by the National Comprehensive Cancer Network as a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning [19]. 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 [20]. The complex nature of CRF has the ability to disrupt all levels of a person s functioning, including physical, mental, emotional and social aspects, theore any intervention that can moderate its effect would significantly enhance the quality of life and recovery process of the patient. The rationale for exercise as a treatment for CRF is that the effects of cancer treatment combined with reduced levels of physical activity during treatment decrease a person s capacity for physical performance. A detrimental cycle is initiated whereby the cancer patient has to expend greater effort relative to maximal ability to perform usual activities, thus leading to higher levels of fatigue [21]. Theore past recommendations for excessive rest during cancer treatment could potentially exacerbate the condition further. 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 [22-25]. A recent RCT, 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 [21]. Decreases 9

21 in levels of subjective fatigue post-intervention have also been reported among mixed groups of cancer survivors in home-based [26] and group-exercise programs [27]. 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 [28]. Fatigue can also be a long-lasting side-effect that persists for a substantial proportion of survivors [29, 30]. In one long-term study, 21% of breast cancer survivors reported persistent problems with fatigue five to 10 years after diagnosis [31]. Exercise interventions conducted post-treatment have obtained similar positive results to those conducted during treatment. In a RCT 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 [32]. Similar trends have also been reported in supervised aerobic interventions conducted 11 months post-treatment [33], and in mixed-type exercise programs carried out at 17 months post-diagnosis [34]. 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 [31]. Research has demonstrated that both depression [35] and cardiovascular problems [36] can be positively influenced by regular physical activity. Physical activity interventions early after treatment theore have the potential to not only reduce fatigue, but to positively impact on these co-morbid conditions in the longer term Breast cancer-related lymphoedema Breast cancer-related lymphoedema (BCRL) has been described as one of the most distressing and unpleasant sequelae following surgery [37]. Both an acute and late complication, it is characterised by the accumulation of protein-rich fluid in the arm after the lymphatic drainage system is interrupted following axillary lymph node dissection or radiation [38]. 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 [39]. Affected women can experience pain, significant swelling of the arm, sensations of tightness or heaviness 10

22 and recurrent skin infections, all of which combine to limit upper-body function. If left unmanaged, symptoms can persist for years and negatively impact a woman s HRQoL [39]. 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. This view stemmed from the belief that axillary dissection or irradiation triggered a global impairment of the lymph drainage system. This impairment would in turn lead to a build-up of lymph, obstruction of lymph flow and the development of BCRL. Theore, if women regularly participated in exercise after surgery (increasing blood flow to the affected arm), lymph production would accumulate, corresponding to an increase in arm volume. However, current research into the exact aetiology and mechanisms of BCRL suggests that its development is multi-factorial and not simply a result of axillary obstruction [40, 41]. Relatively recent studies carried out with breast cancer survivors supports this idea, with no significant reports of increases in lymphoedema development [34, 42-44] or aggravation through exercise participation. [34, 44-46] Intervention studies that have been designed to specifically assess the effect of exercise on BCRL have included both single-group designs [34, 42, 44] and randomisation to intervention or control group [46] or alternative condition (with or without a compression sleeve) [45]. Study sample sizes have been small, ranging from 10 to 31 women, some of whom had pre-existing BCRL. The majority of studies incorporated some form of aerobic exercise, such as walking, running, swimming or cycling, and all involved some form of resistance training. The duration of the interventions ranged from eight weeks to eight months, with training frequency ranging from one to five or more days per week at varying intensity levels. The techniques used to measure the development of BCRL included the sum of arm circumferences [34, 42, 44, 46], the water displacement method [42, 45, 46] and bio-electrical impedance [34, 45]. Assessment was usually carried out using more than one technique. This is important, as currently there is no gold standard to diagnose lymphoedema. Prevalence estimates within one sample of breast cancer patients have been shown to vary from 0.6% to 27.8% depending on the measurement method used [47]. 11

23 Even though these studies involved small sample sizes, different exercise prescriptions and different assessment methods, all concluded 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 [34, 45] Physical capability or fitness Research in women following breast cancer treatment has shown that not only lymphoedema, but level of fitness, impacts on a woman s ability to perform daily tasks that require upper-body function [48]. As regular physical activity has the capacity to increase a woman s fitness, an improvement in the ability to carry out the tasks of daily living would follow. A person s fitness, also known as aerobic fitness, is measured objectively by maximal oxygen uptake [6]. This ers to the body s ability to deliver oxygen to working muscles. Exercise interventions involving cancer patients have assessed aerobic capacity via submaximal graded exercise tests using a treadmill, exercise bike, or step ergometer or through the use of the 12-minute walk test (demonstrated to positively correlate with oxygen uptake). Significant improvements in aerobic capacity of around 15% have been demonstrated for cancer patients using these techniques during adjuvant treatment [21, 22, 24, 27, 43, 49, 50] as well as after treatment [33], and have been positively associated with changes in HRQoL [32]. Most recently, two RCTs 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 [51, 52]. Along with aerobic capacity, exercise interventions that incorporated resistance training have shown improvements in other aspects of physical fitness including strength flexibility [26, 43]. [27, 43] and Weight gain Weight gain has consistently been reported by women undergoing adjuvant chemotherapy. A review looking at this issue reported that significant weight gains 12

24 occurred in 50% to 96% of all patients with early-stage breast cancer who were receiving adjuvant chemotherapy [53]. Weight gains between two and six kilograms appear to be most common [54-56], although much larger gains are not unusual [53]. Weight gain among women with breast cancer is undesirable as it may predispose them to weight-related disorders (e.g. diabetes and hypertension) and the possibility of recurrent disease [57]. The belief that this weight gain is due to increased energy consumption or overeating has not been supported by the literature [54, 58]. Instead, data suggest that chemotherapy-induced weight gain is unique, occurring in the absence of gains in lean tissue or in the presence of lean tissue losses. This type of weight gain has been termed sarcopenic obesity, with the lean body losses occurring predominately in the legs and lower trunk [54, 58]. Regular physical activity has been the strongest predictor of weight stability among breast cancer survivors [54, 56]. 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 [22, 59]. A similar positive outcome using the sum of skinfolds measure was observed among a group of mixedcancer survivors at the completion of a 10-week therapy program. The skinfold measure was significantly reduced among participants assigned to group therapy and exercise, while the skinfold measure significantly increased among participants assigned to group therapy alone [26]. Similar results have also been reported among survivors 14 months post-treatment [32]. 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 [54] Health-related quality of life The assessment of HRQoL allows a more subjective view of a woman s recovery. In the context of oncology, this ers to a patient s appraisal of and satisfaction with her current level of functioning compared to what she perceives to be possible or ideal [60]. Health-related quality of life is a multidimensional concept that generally ers to four connected, but distinct, areas of well-being: physical, functional, emotional and social. The physical dimension relates to bodily function or disruption 13

25 through a combination of disease symptoms, treatment side-effects and general physical well-being. Examples pertinent to breast cancer patients include pain, nausea, and fatigue. Functional well-being ers to one s ability to carry out activities associated with personal needs, ambitions and roles. It incorporates activities of daily living, including walking, feeding, bathing, and responsibilities both in and outside the home. Emotional well-being is comprised of two aspects lecting positive affect (well-being) and negative affect (distress). The fourth main dimension, social well-being, covers a diverse range of areas including perceived social support, maintenance of leisure activities, family functioning and intimacy. Measurement of these four dimensions constitutes an important tool assessing the needs and functioning of cancer survivors, and in combination, offers a valuable global outcome measure of HRQoL. Longitudinal studies of breast cancer patients have described the period after an initial diagnosis and during active treatment to have the most detrimental effect on a woman s HRQoL. After the initial diagnosis, Byar and colleagues described the HRQoL of women in all domains to be significantly lower compared to the general population. While during treatment women who experienced the greatest amount of fatigue also experienced the lowest HRQoL [15]. Acute physical side-effects and psychological distress combine during treatment to impact on HRQoL. In particular, physical functioning has been reported to decrease during the treatment period and to be positively associated with an increase in the number of side-effects perceived by the woman [13]. Consequently, integrating exercise during treatment has the potential to lessen the decline, and hasten the return of HRQoL. Participation in exercise during active cancer treatment has been shown to positively impact on a patient s overall HRQoL and well-being. Two recent RCTs (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 [24], while the second study reported an improvement of six points at six months follow-up [52]. The improvements observed in HRQoL in both studies exceed the clinically defined meaningful change of five points for the FACT-G scale [61]. A 14

26 similar trend has been described for women with advanced-stage disease. A seated exercise intervention reportedly minisimed the decline in global HRQoL during chemotherapy for women diagnosed with stage IV breast cancer compared to controls [28]. While these global ratings provide valuable evidence for the general effect of an exercise intervention, it is important to investigate which specific aspects of HRQoL are influenced the most. The physical and functional well-being aspects of HRQoL appear to be particularly responsive to exercise [24, 26, 43]. While positive influences on social and emotional well-being have also been reported, they lect a lesser extent than observed for physical and functional well-being [26, 43, 52]. A trial involving mixed-cancer survivors assigned to group therapy and exercise or group therapy alone found a significant interaction between the groups for physical and functional well-being outcomes of the FACT-G scale [26]. Post-intervention, the survivors assigned to the exercise group reported significant increases in physical and functional well-being, whereas survivors allocated to group therapy alone experienced a decrease in functional wellbeing and only a small increase in physical well-being. No additional benefits were seen in the aspects of emotional and social well-being beyond that of group therapy alone. More recently, a RCT of a supervised exercise program involving breast cancer patients during active treatment also demonstrated positive improvements in functional well-being. An increase in the magnitude of more than two points (defined as clinically meaningful [61] ) was reported at six month follow-up [52]. Together, these results suggest that physical and functional well-being are the main aspects driving positive changes in global HRQoL. In fact, previous research has described functional well-being to be the least possessed, but most influential, dimension of overall satisfaction with life among cancer survivors [62]. This further highlights the need for exercise to be incorporated into the overall recovery process of the cancer patient. The impact of exercise on the numerous acute symptoms and conditions that combine to influence a person s HRQoL during cancer treatment have also been investigated with varied results observed. Participation in exercise interventions has 15

27 led to significant decreases in pain [27], insomnia [25, 27, 49], diarrhoea [27], depression [23, 43, 50, 63], fatigue [21] and negative emotions [43], while improvements have been reported in levels of vitality [27], positive emotions [43] and body image [64]. Inconsistent findings have been reported for nausea [22, 27, 65] and levels of anxiety, with three studies reporting significant decreases [23, 25, 63], whereas others have reported no statistically or clinically important change [26, 43]. During the first year post-diagnosis, steady improvements in HRQoL are seen after the most acute, treatment-related side-effects have subsided [66, 67]. Nevertheless, specific symptoms, such as insomnia and fatigue, may persist after 12 months, influencing certain aspects of HRQoL well after treatment has completed [30, 31]. Research indicates that by 12 months post-diagnosis the global HRQoL of breast cancer survivors is comparable to women from the general population [68]. However, deficits have been reported in emotional, social, role and cognitive functioning, predominantly affecting younger survivors [69]. With the persistence of some of these physical side-effects and psychological impairments, it is important to know what role exercise might play after treatment has been completed. Randomised controlled trials conducted with breast cancer survivors at least 12 months post-diagnosis have found improvements in global HRQoL [32, 51], physical well-being [32], functional and social well-being [51], selfesteem, happiness, fatigue [32] and body image after exercise participation [33, 34]. This latter finding is particularly notable, as body image disturbance is one aspect that has been reported to persist among breast cancer survivors in the long term [66]. Decreasing trends in distress scores [33, 34] and levels of anxiety [70] have also been reported. 2.4 Prevalence of physical activity among women with breast cancer Influence of measurement choice The positive results from RCT and intervention studies highlighting the beneficial effects of physical activity for the cancer survivor emphasise the need to investigate participation rates in physical activity among cancer survivors. A growing number of studies have looked at the prevalence of physical activity among women with breast cancer, reporting estimates between 9% [71] and 74% [72]. This large variation can be 16