Fatigue is often one of the most common side effects of breast cancer treatment. Nancy Stewart, Master’s prepared RN from NYU Langone Perlmutter Cancer Center, delves into how to recognize cancer-related fatigue, possible causes, and how to manage it. For more information, visit our website at sharecancersupport.org or call our Helpline at 844.ASK.SHARE (844.275.7427).

1. Cancer-Related Fatigue:
HOW TO ADDRESS AND MANAGE IT
NANCY STEWART, MN, RN, CBCN

2. Cancer-Related Fatigue (CRF)
o Defined 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.”
o Differs from non-disease related fatigue
o More severe, disabling, and challenging to relieve
o Not only not relieved by rest but may, in fact, be worsened with rest
o Up to one-third of survivors have significant fatigue 6 years after
treatment
Berger et al., 2012; Bower et al., 2018; Coughlin et al., 2015

3. CRF Criteria
1) A period of 2 weeks or longer within the preceding month during which
significant CRF or diminished energy was experienced each day or almost every
day along with additional CRF-related symptoms
2) The experience of CRF results in significant distress or impairment of function
3) The presence of clinical evidence suggesting that CRF is a consequence of
cancer or cancer therapy
4) CRF is not primarily a consequence of a concurrent psychiatric condition, such
as major depression
Berger at al., 2012

4. CRF is multidimensional
o Physical fatigue
o Affective (emotional) fatigue
o Cognitive fatigue
o Interventions may be effective for one component of CRF and not the
others
Schmidt et al., 2017; Sorensen et al., 2020

5. CRF in breast cancer survivors (BCS)
o One of the most frequent and distressing symptoms
o As many as 95% of BCS experience cancer-related fatigue at some point
in their disease trajectory
o Symptom onset may occur during or remote from treatment
o Lingering effect - does not resolve with tumor control or treatment
cessation
o Impacts quality of life, interpersonal relationships, and work productivity
Berger at al., 2012; Inglis et al., 2020; Person et al., 2020

6. What Causes CRF?
o Multifactorial biochemical, physiological, psychological, psychosocial, and
behavioral factors:
• Tumor characteristics and stage
• Direct effects of cancer
• Dysfunctional secretion of endocrine and inflammatory molecules
• Comorbidities
• Psychosocial issues
• Side effects of treatment
Huang et al., 2019; Inglis et al., 2020; Person et al., 2020; Puigpinos-Riera et al., 2020; Schmidt et al., 2017

7. Variability in CRF among BCS
• Low or very low symptoms throughout and following treatment –
comparable to women of similar age with no cancer history
• High fatigue during treatment, followed by recovery
• Late onset fatigue
• Persistently elevated fatigue
o Psychosocial factors were strongest predictors of group membership
o Treatment types impact fatigue trajectories
Bower et al., 2018

8. Factors Affecting Physical Health/Quality of Life in BCS
o Depression
o Anxiety
o Sleep disturbance
o Medical comorbidities
o Low socioeconomic status
o Lack of health insurance
Coughlin et al., 2015; Fox et al., 2020; Huang et al., 2019

9. Risk Factors for CRF
o Elevated BMI
o Poor sleep quality
o Depression/anxiety
o Childhood adversity
o Low socioeconomic status
o Comorbidities
Berger at al., 2012; Bowers at al., 2018; Person et al., 2020; Puigpinos-Riera et
al., 2019; Williams et al., 2021
o Spiritual suffering
o Living alone
o <50 years of age
o Physical inactivity
o Pre-existing fatigue

10. Treatable Contributing Factors
o Side effects of medication
o Pain
o Anemia
o Comorbidities – hypertension, hypothyroid
o Nutritional imbalances
o Mental health issues/emotional distress
o Requires medical evaluation and cooperation between oncologists, PCPs,
and mental health providers
Berger et al., 2012; Schmidt et al., 2017

11. Symptom Clusters
o Two or more concurrent symptoms that are related to one another
o Hasten or potentiate the effects of the other(s)
o Sleep problems, depression, CRF, and poorer overall quality of life
o Hot flashes, pain, CRF
o Fatigue, anxiety, and decreased quality of life
o Pain, fatigue, and psychological distress - associated with premenopausal
status, working less than full-time, lymphedema, and disability
Berger et al., 2012; Bjerkeset et al., 2020; Fox et al., 2020; Williams et al., 2021

12. Depression, Anxiety, and CRF
o Highly associated with affective fatigue
o History of depression and depressive symptoms predict post-treatment
fatigue
o Use of psycho-pharmaceuticals associated with CRF
o Pattern of adjustment to stressful life events is predictive for CRF
o Anxiety and CRF are associated with poor treatment adherence
o Resilience is protective against CRF
Bower et al., 2018; Puigpinos-Riera et al., 2020; Schmidt et al., 2017; Williams et al., 2021

13. Sleep Disturbance and CRF
o Multifactorial and interconnected
o Interventions should be targeted to cause of poor sleep quality
o Sleep disturbance due to physical fatigue versus affective fatigue
o Sleep quality measured during chemotherapy showed deficits in those with
both low and high self-reported symptoms
o Subjective sleep quality may differ from objective sleep quality
o Sleep disturbance associated with younger age group
o Less symptom burden in married participants
o Positive correlation with obesity and medical comorbidities
Fox et al., 2020

14. Hot Flashes
o Common for women undergoing endocrine therapy
o Impact both physical and cognitive fatigue
o Associated with sleep disturbance and CRF
o Acupuncture might benefit, but more research is needed
o Supplements may improve symptoms
Berger et al., 2012; Schmidt et al., 2017

15. Social Support and CRF
o Social support improves quality of life in BCS
o Support from spouses, partners, children, siblings, friends, colleagues,
and healthcare workers has been shown to be beneficial to feelings of
social support
o Lack of social support is associated with mental fatigue but not physical
fatigue
o Being single increases CRF
Sorensen et al., 2020

16. Population-Specific Considerations
o Fewer studies focus on the experience of African-American BCS
o African-American BCS have higher rates of obesity and lower rates of
physical activity than white survivors
o Spirituality and faith-based support
o Strong religious beliefs are protective against CRF
Coughlin et al., 2015; Puigpinos-Riera et al., 2020

17. Age and CRF
o Premenopausal women are at increased risk for CRF
• Premature menopause
• Infertility
• Risk of recurrence
• Caregiver responsibilities
• Concerns about employment/career
o Different issues for postmenopausal women
Coughlin et al., 2015; Puigpinos-Riera et al., 2020; Sorensen et al., 2020

18. Obesity and CRF
o Often present at diagnosis – risk factor for breast cancer and cancer
recurrence
o Weight gain is common in post-menopausal women
o May occur as a side effect of breast cancer treatment
o Associated with chronic inflammation
o Higher BMI at baseline is associated with increased physical fatigue
before, during, and after treatment
Coughlin et al., 2015; Inglis et al., 2020; Schmidt et al., 2017

19. CRF and chemotherapy
o CRF is a common symptom in BCS undergoing chemo
o Fatigue peaks about 4 days after chemo, then gradually subsides
o For some BCS, fatigue does not subside prior to the next cycle and
accumulates over time
Hsiang-Pin et al., 2019

20. Benefits of Physical Activity for BCS
o Inverse relationship between physical activity and recurrence and breast
cancer-related death
o Greater physical activity associated with decrease in recurrence and
mortality compared to less activity
o During breast cancer treatment, early intervention can provide long-
lasting benefits that last after treatment is completed
Berger et al., 2012; Coughlin et al., 2015; Kim et al., 2019; Schmidt et al., 2015

21. Exercise and CRF
o The most effective intervention for CRF (moderate benefit)
o Aerobic and resistance exercise, both jointly and separately, have
demonstrated effectiveness
o Performed in a supervised or home-based environment
o Should be individualized, with gradual progression of intensity
o Effects depend on stage of treatment and type of intervention
o Majority of BCS do not meet physical activity guidelines
Berger at el., 2012; Ehlers et al., 2020; Gebruers et al., 2018; Hagstrom et al., 2016; Huang et al., 2019; Kim et al., 2019; Schmidt et al., 2015

22. Exercise Recommendations
o Moderate intensity to increase heart rate
o 30 min/day or 10 min, 3 times/day
o 5 days/week
Huang et al., 2019

23. Benefits of Exercise for BCS
Positive effects on:
• Body image/self-esteem
• Emotional well-being
• Sexuality
• Sleep disturbances
• Social functioning
• Anxiety
• Pain
Coughlin et al., 2015

24. How Does Exercise Help?
o Inactivity leads to deconditioning, muscle wasting, and sleep disturbance
o Increased levels of moderate to strenuous activity may mitigate fatigue
through various metabolic and inflammatory pathways
o Improvements in muscle strength, aerobic capacity, and fatigue
o Beneficial in activities of daily living
Berger et al., 2012; Gebruers et al., 2018; Huang et al., 2019; Juvet et al., 2017

25. Psychosocial Benefits
o Increased self-esteem and health-related quality of life
o Decreased anxiety and depression
o Peer-based exercise programs demonstrate benefits from interacting
with other BCS
o Decreased affective and cognitive fatigue, although to a lesser degree
than physical fatigue
Gebruers et al., 2018; Juvet et al., 2017; Kim et al., 2019; Schmidt et al., 2017

26. Exercise Throughout the Treatment Continuum
o BCS who were physically active prior to diagnosis were more likely to
achieve desired activity levels
o Interventions implemented during adjuvant chemotherapy
demonstrated a small to moderate effect
o Resistance exercise during adjuvant radiotherapy demonstrated
reduction in CRF
o Benefits increase for programs started after treatment is completed
o Wearable sensors and mobile health tools provide an opportunity to
engage in physical activity
Ehlers et al., 2020; Gebruers et al., 2018; Kim et al., 2019; Juvet et al., 2017

27. Barriers to Exercise
o Treatment-related side effects – dizziness, nausea, chemotherapy-
induced neuropathy (tingling in the hands and feet), joint pain, too tired
to exercise
o Class not tailored to BCS – feel like an outsider (body image, hair loss)
o Decreased arm mobility/pain
o Concern about lymphedema
o Prior sedentary lifestyle
Kim et al., 2019

28. Resistance Exercise (RE) and CRF
o Counteracts muscle wasting, improves deficits in affected limb and functional well-
being in BCS
o RE during adjuvant chemotherapy decreased CRF and improved quality of life as
compared to a relaxation control group
o Little demonstrated benefit for affective or cognitive fatigue
o RE improved CRF and quality of life in previously sedentary BCS
o Moderate-intensity RE after treatment showed greater benefits than lower-intensity
RE, or aerobic exercise at any intensity
o Resistance training alone, or in combination with aerobic conditioning, seems to
provide the best results with regard to physical performance outcomes and perceived
fatigue
Gebruers et al., 2018; Hagstrom et al. 2016; Juvet et al., 2017; Schmidt et al., 2015

29. High Intensity Interval Training (HIIT) During
Chemotherapy and CRF
o 16 week program, broken into 3 groups:
• Resistance training & HIIT
• Aerobic exercise & HIIT
• Usual care
o Resistance training & HIIT prevented increases in physical and cognitive
fatigue
o Aerobic exercise & HIIT decreased pain and improved emotional
functioning
Mijwel et al., 2017

30. Aerobic Exercise and CRF
o Improves both physical and affective fatigue
o May impact CRF through:
• Mobilizing body fat
• Increased insulin sensitivity/glucose uptake
• Decreasing inflammatory cytokines
Berger et al., 2012; Mijwel et al., 2017

31. 12-week Home-Based Brisk Walking Program
o Women undergoing adjuvant chemotherapy
o Progressed from 3-5 times/week, 15-40 min/session
o Fatigue levels increased over time for both walkers and control groups
o Walkers demonstrated less fatigue than control group
o Effects lasted 9 months after completion of exercise program
o Women who exercised prior to their diagnosis had less fatigue than
those who exercised less
Huang et al., 2019

32. Lymphedema Concerns
o Outdated recommendations to “not lift anything heavy” with the
affected arm
o Endurance training in affected limb improves quality of life in BCS
o Supervised and progressive resistance exercise is beneficial in regaining
strength and functioning on the affected side
o Resistance training has not been shown to increase incidence of
lymphedema
Puigpinos-Riera et al., 2020; Schmidt et al., 2015

33. Psychosocial and Complementary Interventions
o Cognitive Behavioral Therapy – not readily available, can be costly
o Counseling
o Support groups
o Expressive therapies
o Relaxation/Imagery
o Acupressure/Acupuncture
o Mostly weak evidence, more research needed
Berger et al., 2012; Puigpinos-Riera et al., 2020; Schmidt et al., 2017

34. Yoga and CRF
o 8-week supervised program showed a large effect on physical fatigue in
the post-treatment setting, small effect on women undergoing treatment
o Medium impact on cognitive fatigue
o No impact on emotional fatigue
Dong et al., 2019

35. Swedish Massage Therapy
o One 6-week study showed massage reduces CRF compared to control
groups receiving either a light-touch intervention or on a wait-list
o Prior studies have demonstrated that massage decreases depression,
anxiety, and pain in BCS
o Further studies needed
Kinkead et al., 2018

36. Art Therapy
o Offers a way to express feelings that are difficult to communicate
verbally
o Includes music, visual arts, dance & movement, sculpture, poetry, drama
o May provide benefits for BCS with respect to anxiety, depression, and
fatigue
o Studies have been short-term and in group settings
o More studies needed
Tang et al., 2018

37. Music Therapy and Radiotherapy-Induced
Fatigue
o Individual 30-40 minute sessions with a professional music therapist
o Twice weekly, at three different times during treatment
o Each session progressed through slow tempo songs chosen by therapist,
favorite songs chosen by the participant, faster tempo songs chosen by
the therapist, and concluded with a song performed by an orchestra and
singer
o Improved fatigue, symptoms of depression, and quality of life versus
control group
Alcantara-Silva et al., 2018

38. Diet
o Reduced risk of non-cancer mortality with healthy diet
o In post-menopausal women, lower diet quality is associated with shorter
sleep duration
o In one study, higher soy and cruciferous vegetables (broccoli,
cauliflower) intake was associated with decreased menopausal symptoms
and fatigue in white BCS
Coughlin et al., 2015; Nomura et al., 2018; Pereira et al., 2018; Zick et al., 2017

39. Fatigue-Reduction Diet
o Improved fatigue and sleep quality in BCS when compared to control
group during a 3-month intervention
• Researchers hypothesize that a diet high in antioxidants decreases
inflammation and thus, alleviates fatigue
• Maintained baseline calories, but replaced typical foods with fatty fish,
nuts and seeds, whole grains, fruits, and vegetables (particularly green
leafy vegetables/tomatoes)
Zick et al., 2017

40. Dietary Supplements and CRF
o A systematic review aimed to identify dietary supplements beneficial in CRF
• Chlorella extracts and granules reduced fatigue in one study
• Coconut oil was beneficial in one study of patients receiving chemotherapy
• Ginseng may provide a small benefit
• Guarana studies show mixed results and adverse side effects
• CoQ 10 with vitamin E did not reduce CRF
• Acetyl-l-carnitine NOT recommended – risks outweigh the benefits
• Discuss with your oncologist - supplements may interact negatively with
oncologic treatment
Pereira et al., 2018

41. In Summary
o No magic bullet
o CRF is complex and not well-understood
o Exercise shows the biggest reduction in symptoms
o Resistance exercise, coupled with aerobic exercise and/or HIIT, is
recommended
o Increase consumption of omega-3 rich fish, nuts, and seeds, whole
grains, fruits, and vegetables
o Engage in activities that improve your sense of well-being and provide
social support

42. Thank you!

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