|Ahead of print publication
Perception, magnitude, and implications of cancer-related fatigue in breast cancer survivors: Study from a developing country
Alok Gupta1, Shaik Maheboob Hussain1, Harleen Kaur Nayyar1, Neha Sonthwal2, Radhika Manaktala3, Harit Chaturvedi4
1 Department of Medical Oncology, Max Institute of Cancer Care, Max Super Specialty Hospital, New Delhi, India
2 Department of Clinical Research, Max Institute of Cancer Care, Max Super Specialty Hospital, New Delhi, India
3 Department of Patient Care Services, Patient Support Group, Max Institute of Cancer Care, Max Super Specialty Hospital, Saket, New Delhi, India
4 Department of Surgical Oncology, Max Institute of Cancer Care, Max Super Specialty Hospital, New Delhi, India
|Date of Submission||05-Mar-2019|
|Date of Acceptance||14-Oct-2019|
|Date of Web Publication||09-Jun-2020|
Max Institute of Cancer Care, Max Super Specialty Hospital, Saket, New Delhi 110 017
Source of Support: None, Conflict of Interest: None
Background: We have analyzed perceptions, magnitude, interventions adopted, and overall implications of cancer-related fatigue (CRF) in breast cancer survivors (BCSs).
Methodology: BCSs who attended follow-up clinic at our institute between January and June 2018 were asked to fill a questionnaire focused on assessing an individual's perception, severity, potential causes, implications on quality of life, and measures taken to deal with CRF.
Results: Sixty-five patients were included. Fifty-four (83%) had undergone surgery, 59 (91%) chemotherapy, 43 (66%) radiation therapy, and 36 (55%) hormonal/targeted therapy. Sixty-two (95%) patients experienced any grade CRF. Fifty-five (85%) patients experienced moderate to severe CRF affecting work (58%) and activities of daily living (27%). CRF was perceived as generalized weakness by 54 (83%) patients, diminished concentration/attention span by 24 (37%) patients, decreased motivation and interest in usual activities by 29 (45%) patients, and emotional labiality by 16 (25%) patients. Fifty-six patients (86%) believed that fatigue was due to the effect of cancer treatment on the body, while only 8 (12%) attributed it to underlying cancer. CRF had negative impact on mood, daily activities, interpersonal relationships, and professional work in 40 (62%), 39 (60%), 13 (20%), and 10 (15%) patients, respectively. Measures taken to overcome CRF were increased physical exercise, psychosocial interventions, mind–body interventions, and pharmacological interventions in 32 (49%), 8 (12%), 28 (43), and 17 (26%) patients, respectively. Thirty-nine (60%) patients reported persistence of CRF after completion of treatment while it took up to 6 months, 6–12 months, and more than 12 months for resolution of CRF in 13, 10, and 3 patients, respectively.
Conclusion: Development and persistence of CRF remains a major health concern, and current interventions are not able to mitigate this problem. Further research in this field is warranted.
Keywords: Breast cancer treatment, cancer-related fatigue, cancer survivorship
|How to cite this URL:|
Gupta A, Hussain SM, Nayyar HK, Sonthwal N, Manaktala R, Chaturvedi H. Perception, magnitude, and implications of cancer-related fatigue in breast cancer survivors: Study from a developing country. J Can Res Ther [Epub ahead of print] [cited 2020 Sep 19]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=286248
| > Introduction|| |
Cancer-related fatigue (CRF) is among the most common and distressful symptom among cancer patients. This can be seen during the cancer journey and may continue even after cancer treatment has been completed. The National Comprehensive Cancer Network defines CRF as “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.” It has an abstruse impact on patient's quality of life (QOL) affecting functional performance, mood, and overall behavior. CRF is seen in nearly 30%–70% of all patients at some point during their cancer journey, but in patients with metastatic disease, the prevalence of CRF exceeds 75%. It is believed that the pathophysiology of CRF is multifactorial, involving a complex interplay of biological and body system factors and hence is less well understood.
Unfortunately, CRF as a problem is highly underreported, under perceived, and in this way, undertreated. It is profoundly neglected both by the patients and the doctor, and therefore, explicit CRF-directed approaches are only sometimes advised. Furthermore, sometimes, the doctor may misinterpret CRF to be simply pain which may hamper sufficient treatment of this mind-boggling indication. Variations in how researchers and clinicians conceptualize this debilitating symptom have resulted in the development of different tools for assessing CRF; however, there is no gold standard.
Therefore, we tried to analyze perceptions, magnitude, interventions adopted, and overall implications of CRF in breast cancer survivors (BCSs).
| > Methodology|| |
The present study was an observational, cross-sectional, questionnaire-based study conducted among BCSs who attended breast cancer follow-up clinic at our cancer institute between January and March 2018. All patients were briefed about the nature of the study, and the patients who agreed to part of the study were enrolled. The questionnaire was well validated and focused on assessing an individual's perception, severity, potential causes, implications on QOL, and measures taken to deal with CRF [Figure 1]. Patients were allowed to ask questions regarding their participation in the study. The personal right to withdraw from the study at any moment was ensured without repercussions. The anonymity and confidentiality of every patient were maintained. The responses to the question were compiled in Microsoft excel version 2015 and analyzed, and accordingly, results were prepared.
| > Results|| |
Sixty-five patients completed the CRF questionnaire [Table 1]. The median age of patients was 52 years. Among the enrolled patients, 54 (83%) had undergone surgery, 59 (91%) chemotherapy, 43 (66%) radiation therapy, and 36 (55%) hormonal/targeted therapy. Sixty-two (95%) patients experienced any grade CRF. Fifty-five (85%) patients experienced moderate to severe CRF affecting work (58%) and activities of daily living (27%). CRF was perceived as generalized weakness by 54 (83%) patients, diminished concentration/attention span by 24 (37%) patients, decreased motivation and interest in usual activities by 29 (45%) patients, and emotional lability by 16 (25%) patients. Fifty-six patients (86%) believed that fatigue was due to the effect of cancer treatment on the body, while only 8 (12%) attributed it to underlying cancer. Twenty-one (32%) patients also attributed it to psychosocial factors and 5 (8%) to genetic/environmental factors. CRF had negative impact on mood, daily activities, interpersonal relationships, and professional work in 40 (62%), 39 (60%), 13 (20%), and 10 (15%) patients, respectively. Measures taken to overcome CRF were increased physical exercise, psychosocial interventions, mind–body interventions, and pharmacological interventions in 32 (49%), 8 (12%), 28 (43), and 17 (26%) patients, respectively. Thirty-nine (60%) patients reported persistence of CRF after completion of treatment while it took up to 6 months, 6–12 months, and more than 12 months for resolution of CRF in 13, 10, and 3 patients, respectively.
| > Discussion|| |
The present study was among the few studies conducted to find perception, magnitude, and implication of fatigue among BCS patients. Majority of the enrolled patients were elderly with the median age of 52 years, which means increasing age is a risk factor for fatigue in breast cancer patients. Therefore, health professionals ought to be aware of the likelihood of more prominent fatigue in older cancer survivors. In general, aging results in functional and metabolic change in the body system which leads to deterioration of physiological systems. While there is no universally accepted and recognized threshold of old age, it is considered that the deterioration of biological and physiological systems begins after the age of 45–50 years. Aging is also related to disturbed circadian rhythms and sleep quality, characterized by decrease in nighttime sleep quality and decrease in day time alertness, which stimulates higher fatigue.,,
Fatigue of any kind or severity was reported in 95% of patients enrolled in our study. Such high rate of prevalence was reported not only during the adjuvant therapy but also after completing the therapy. In a study by Sitzia and Huggins, fatigue incidence was 90% in breast cancer patients receiving six cycles of chemotherapy and severity remained stable throughout the treatment cycles. Jacobsen et al. also reported similar results, although the prevalence and severity of fatigue significantly increased at the starting of chemotherapy, after which the prevalence of fatigue showed a stable pattern. Two systemic reviews widely examined the prevalence of fatigue in BCS. Minton and Stone in their systematic review of 18 studies reported that fatigue is a problem for a significant percentage of BCS, with some studies reported prevalence up to 50%. Ganz and Bower based on three studies reported that approximately one in three BCS experience fatigue symptoms.
Chemotherapy was reported as the most common cause related to fatigue in our study, as 91% of patients were on chemotherapy who reported the presence of fatigue followed by those who underwent surgery (83%) and radiotherapy (66%). The reported incidence of CRF, available in literature, varies from 30% to 91% in patients receiving chemotherapy, 25%–83% in patients receiving radiation therapy, and 59%–83% in patients undergoing combined chemo and radiation therapy. The use of different treatment modality including different chemotherapeutic agents and regimes may be one of the reasons for this variation. Inflammation had shown to play a critical role in the pathophysiology of fatigue in cancer patient. In a study conducted among patients undergoing radiotherapy for early-stage breast or prostate cancer, increase in serum C-reactive protein and interleukin (IL)-1 were related to increase in severity of fatigue. Similarly, among breast cancer patients undergoing chemotherapy, changes in IL-6 were related to changes in fatigue severity and intensity. Wang et al.,, examined symptoms and inflammatory markers in patients undergoing combined radiation and chemotherapy therapy for locally advanced colorectal and lung cancer. They reported acute increases inflammatory marker related to fatigue and other symptoms.
Despite the fact that fatigue is common and frequently debilitating symptom in cancer patients, it is perceived diversely by various patients. In our study, it was perceived as generalized weakness by majority (83%) of the patients, some patients also considered fatigue as a state of decreased concentration/attention span and decreased motivation and interest in usual day–to-day activity. Since various factors are attributed to fatigue, it is rather difficult to find a comprehensive definition of fatigue in the literature, and hence, there are various definitions attributed to this complex phenomenon. Furthermore, there are other terms which are used interchangeably with fatigue and which are commonly reported by breast cancer patients such as drowsiness or somnolence or sleepiness fatigue is also often overlapped and characterized by lack of power or strength, lethargy, feeling tired, faded fine, and downside in concentrating. Thus, fatigue consists of subjective component which is rather difficult to define and explain.
Severity of fatigue was assessed in our study using 4-point scaling system depending on its ability to interfere with work and daily activity. Majority of the patients, i.e., 55 (85%) experienced moderate to severe fatigue affecting work (58%) and activities of daily living (27%). CRF often affects patients' QOL, as it often coexists with other debilitating yet common symptoms such as pain and depression, reducing the patient's ability to work and also loss of interest in his/her personal and social life.
Fatigue can be both a manifestation of most cancer treatment and a symptom due to most cancers themselves, which can also cause a misattribution of the symptoms of fatigue and the impact of those on the functioning of patients. Similarly, in our study, majority of patients (86%) believed fatigue was due to the effect of cancer treatment on the body, while only 8 (12%) patients attributed it to underlying cancer. Some patients also believed that fatigue is attributed to psychosocial and genetic/environmental factor. Numerous studies have highlighted a link between CRF and increased levels of depression, anxiety, and mood disturbance., These psychological symptoms can have an effect on a patient's capability to perform day-to-day activity, including self-care, and may actually have a bad impact on treatment consequences by lowering survival instances. While psychological distress has been proven to be a susceptible predictor of the levels of posttreatment fatigue, any causal relationship remains unclear.
CRF has been rated as more troublesome and is considered to have a greater negative impact on patients' daily activities and QOL than other cancer-related symptoms, such as pain, nausea, vomiting, and depression.,, In our study, CRF reported to have negative impact on mood, daily activities, interpersonal relationships, and professional work in 40 (62%), 39 (60%), 13 (20%), and 10 (15%) patients, respectively. This is probably due to the effect of fatigue on the physical functioning of patient. In a study conducted among 379 patients with cancer and a history of chemotherapy, almost all patients with fatigue (91%) felt that it averted them from “normal” lifestyles and 88% felt that their fatigue had changed their day-by-day activity with significant impairment in their potential to finish a variety of activity of daily living, such as preparing food, cleansing the residence, mild lifting, and social activities with friends and own family.
When asked, did fatigue improve completely after completion of cancer treatment, thirty-nine (60%) patients reported persistence of CRF after completion of treatment while it took up to 6 months, 6–12 months, and more than 12 months for resolution of CRF in 13, 10, and 3 patients, respectively. A recent study suggested that fatigue may also undergo for up to 10 years after breast cancer diagnosis. Two national surveys commissioned by The Fatigue Coalition, to look at the importance of fatigue for patients with most cancers and their caregivers reported even patients who had completed treatment more than 2 years earlier remained considerably symptomatic. A 3-year follow-up study conducted by Goedendorp et al. among BCSs reported that fatigue did not diminish over time in patients who received chemotherapy whereas they remained stable and lower in the patients who received only radiotherapy and in women with no history of cancer. Goldstein et al. in their study found that CRF persists for 12 months or more after cessation of computed tomography treatment in 32% of patients.
While couple of elements have been found to be related with most CRF, it has yet to be determined which factors predispose, precipitate, or exacerbate/maintain the patient's experience of fatigue. The treatment of CRF is complicated due to the hyperlinks located among fatigue and numerous physical and psychological variables. In our study, measures taken to overcome CRF by our patients were increased physical exercise, psychosocial interventions, mind–body interventions, and pharmacological interventions. Thus, a multidisciplinary approach is needed for the effective treatment of CRF which target not only the physical symptoms but also which will target mind, body, and spirit of cancer patient.
| > Conclusion|| |
Development and persistence of moderate to severe intensity CRF remains a major health concern in BCSs. It impacts multiple aspects of QOL of cancer survivors. Studies such as ours may lead to increased awareness of the need for the assessment of fatigue symptoms on an ongoing basis in patients with cancer in the clinic.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al.
Impact of cancer-related fatigue on the lives of patients: New findings from the fatigue coalition. Oncologist 2000;5:353-60.
Piper BF, Cella D. Cancer-related fatigue: Definitions and clinical subtypes. J Natl Compr Canc Netw 2010;8:958-66.
Berger AM, Abernethy AP, Atkinson A, Barsevick AM, Breitbart WS, Cella D, et al.
NCCN clinical practice guidelines cancer-related fatigue. J Natl Compr Canc Netw 2010;8:904-31.
Kapoor A, Singhal MK, Bagri PK, Narayan S, Beniwal S, Kumar HS. Cancer related fatigue: A ubiquitous problem yet so under reported, under recognized and under treated. South Asian J Cancer 2015;4:21-3.
] [Full text]
Weinert D. Age-dependent changes of the circadian system. Chronobiol Int 2000;17:261-83.
Dawson D, Ian Noy Y, Härmä M, Akerstedt T, Belenky G. Modelling fatigue and the use of fatigue models in work settings. Accid Anal Prev 2011;43:549-64.
Viola AU, Chellappa SL, Archer SN, Pugin F, Götz T, Dijk DJ, et al.
Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: Effect of a PER3 polymorphism. Neurobiol Aging 2012;33:1010.e17-27.
Sitzia J, Huggins L. Side effects of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy for breast cancer. Cancer Pract 1998;6:13-21.
Jacobsen PB, Hann DM, Azzarello LM, Horton J, Balducci L, Lyman GH. Fatigue in women receiving adjuvant chemotherapy for breast cancer: Characteristics, course, and correlates. J Pain Symptom Manage 1999;18:233-42.
Minton O, Stone P. How common is fatigue in disease-free breast cancer survivors? A systematic review of the literature. Breast Cancer Res Treat 2008;112:5-13.
Ganz PA, Bower JE. Cancer related fatigue: A focus on breast cancer and Hodgkin's disease survivors. Acta Oncol 2007;46:474-9.
Bower JE, Ganz PA, Tao ML, Hu W, Belin TR, Sepah S, et al.
Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin Cancer Res 2009;15:5534-40.
Liu L, Mills PJ, Rissling M, Fiorentino L, Natarajan L, Dimsdale JE, et al.
Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy. Brain Behav Immun 2012;26:706-13.
Wang XS, Shi Q, Williams LA, Mao L, Cleeland CS, Komaki RR, et al.
Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy. Brain Behav Immun 2010;24:968-74.
Wang XS, Williams LA, Krishnan S, Liao Z, Liu P, Mao L, et al.
Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. Brain Behav Immun 2012;26:699-705.
Wang XS, Shi Q, Williams LA, Cleeland CS, Mobley GM, Reuben JM, et al.
Serum interleukin-6 predicts the development of multiple symptoms at nadir of allogeneic hematopoietic stem cell transplantation. Cancer 2008;113:2102-9.
Bardwell WA, Ancoli-Israel S. Breast cancer and fatigue. Sleep Med Clin 2008;3:61-71.
Williams LA, Bohac C, Hunter S, Cella D. Patient and health care provider perceptions of cancer-related fatigue and pain. Support Care Cancer 2016;24:4357-63.
Dimeo FC, Stieglitz RD, Novelli-Fischer U, Fetscher S, Keul J. Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy. Cancer 1999;85:2273-7.
Stone P, Richards M, A'Hern R, Hardy J. A study to investigate the prevalence, severity and correlates of fatigue among patients with cancer in comparison with a control group of volunteers without cancer. Ann Oncol 2000;11:561-7.
McDaniel JS, Musselman DL, Porter MR, Reed DA, Nemeroff CB. Depression in patients with cancer. Diagnosis, biology, and treatment. Arch Gen Psychiatry 1995;52:89-99.
Irvine DM, Vincent L, Graydon JE, Bubela N. Fatigue in women with breast cancer receiving radiation therapy. Cancer Nurs 1998;21:127-35.
Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al
. Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition. In: Marty M, Pecorelli S, editors. Fatigue and Cancer. Amsterdam, Netherlands: Elsevier; 2001. p. 3-16.
Stone P, Richardson A, Ream E, Smith AG, Kerr DJ, Kearney N, et al.
Cancer-related fatigue: Inevitable, unimportant and untreatable? Results of a multi-centre patient survey. Cancer fatigue forum. Ann Oncol 2000;11:971-5.
Vogelzang NJ, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ, et al.
Patient, caregiver, and oncologist perceptions of cancer-related fatigue: Results of a tripart assessment survey. The fatigue coalition. Semin Hematol 1997;34:4-12.
Penttinen HM, Saarto T, Kellokumpu-Lehtinen P, Blomqvist C, Huovinen R, Kautiainen H, et al.
Quality of life and physical performance and activity of breast cancer patients after adjuvant treatments. Psychooncology 2011;20:1211-20.
Curt GA. The impact of fatigue on patients with cancer: Overview of FATIGUE 1 and 2. Oncologist 2000;5 Suppl 2:9-12.
Goedendorp MM, Andrykowski MA, Donovan KA, Jim HS, Phillips KM, Small BJ, et al.
Prolonged impact of chemotherapy on fatigue in breast cancer survivors: A longitudinal comparison with radiotherapy-treated breast cancer survivors and noncancer controls. Cancer 2012;118:3833-41.
Goldstein D, Bennett BK, Webber K, Boyle F, de Souza PL, Wilcken NR, et al.
Cancer-related fatigue in women with breast cancer: Outcomes of a 5-year prospective cohort study. J Clin Oncol 2012;30:1805-12.