Oncology Rehab Conference Title: Rehabilitation Issues in Breast Cancer Survivorship Author: Maryam Lustberg

1. Rehabilitation Issues In
Breast Cancer Survivorship
Maryam B Lustberg, MD MPH
Medical Director of Survivorship
The OSU Comprehensive Cancer Center

2. Outline
 Recent updates in breast cancer management
 Common symptoms faced by breast cancer survivors:
- Chemotherapy induced neuropathy
- Chemobrain
- Arthralgias
 Exercise prescription
 Current challenges and future direction in Oncorehab and breast
cancer survivorship

3. Recent Updates in Breast
Cancer Management

4. Breast Cancer is a Common Disease of Women
Incidence of Invasive Breast cancer in the US 231, 840 (~124.8 per 100,000)
Incidence of invasive Breast Cancer in the World 1,300,000 per year
Life time Risk 1 in 8 women
Prevalence 2,747,459
Median Age of Diagnosis 61
Mortality in US 40,290
Based on Survaillance Epidemiology and End Result Database; American Cancer Society, Cancer Facts & Figures; 2015

5. Breast cancer treatment modalities
Treatment of Operable Breast Cancer
Surgery Chemotherapy
Local Control
Radiation
Therapy
Distant Control
Endocrine
Therapy
Lumpectomy Mastectomy

6. Stages of Breast Cancer
Localized Disease:
 Distribution - 60%
 5-Year Survival – 98%
Locally Advanced
 Distribution 33%
 5-year Survival 84%
Metastatic Disease
 Distribution 5-7%
 5-year survival 23%
Based on Survaillance Epidemiology and End Result Database

7. Breast Cancer
ER+
65-75%
HER2+
15-20%
Basaloid
15%
Most Important Paradigm Shift:
Breast Cancer is not one disease
“Triple Negative”
BRCA 1
P53
“A”
“B”

8. Berry et al NEJM 2005

9. Breast Cancer: Then and Now
Then
 ~75% of women survived ≥5 years
 Mastectomy was the only surgical option
 Single-agent chemotherapy was standard of
care
 Hormonal therapy with tamoxifen was
under investigation only
 Genes involved in breast cancer
development have not yet been identified
Now
 ~95% of women survive ≥5 years
 Lumpectomy is available
 Combination chemotherapy is the standard
of care
 Hormonal therapy is widely used
 Receptor-based therapy is widely used
 Understanding of genetic components have
expanded
National Cancer Institute. Available at: http://www.cancer.gov/cancertopics/cancer-advances-in-focus/breast.

10. Breast Cancer Systemic Therapy Options
 Endocrine Therapy
 Chemotherapy
 Biologics (trastuzumab, pertuzumab)

11. Pertuzumab
Hubbard SR. Cancer Cell. 2005;7:287-288.
Pertuzumab-HER2 Complex Trastuzumab-HER2 Complex
Pertuzumab
Dimerization domain
Trastuzumab
III
II
I
 Inhibits HER2 dimerization with other HER family
receptors (particularly HER3)
 Activates ADCC
 Inhibits multiple HER-mediated signaling
pathways
 Activates ADCC
 Inhibits HER-mediated signaling pathways
 Prevents HER2 domain cleavage
III
II
I
IV IV

12. Highly potent cytotoxic agent
Cytotoxic agent: DM1
Monoclonal antibody: Trastuzumab
Target expression: HER2
Systemically stable
Linker: SMCC
T-DM1
Average drug:antibody
ratio ≅ 3.5:1
Trastuzumab-DM1: Novel Antibody-Drug
Conjugate
Trastuzumab
MCCDM1
MCC (Non-reducible thioether bond to a linker
molecule)Meeream M., et al. J clin Oncol. 2008; 26 (May 20 suppl; abstract 1028)

13. Good news
 We are using less chemotherapy and smarter targeted therapies
 Selecting for higher risk tumors using tissue profiling (Oncotype Dx)

14. Bad news
 Our newer endocrine therapy options are more toxic than tamoxifen
 More arthralgias
 More fatigue
 More weight gain

15. Bad news
 When we do use chemotherapy, our regimens in some ways have
become more dose dense and toxic
 Longer duration of therapy: 1 year for Her2 + disease

16. Good news
 We know more about the benefits of lifestyle modifications- nutrition
and exercise than ever before
 Cancer diagnosis and treatment are filled with teachable moments
and opportunities for change

17. Bad news
 It’s not so easy to change
 Many survivors continue to struggle and are not facing the effects of
treatment related toxicities (neuropathy, chemobrain, fatigue etc)

18. Common symptoms faced by
breast cancer survivors

19. Potential Side Effects from Breast Cancer Therapy
Hayes DF. N Engl J Med. 2007;356:2505-2513.
Hot flashes/night sweats
Arthralgia/joint symptoms
Sexual dysfunction
Cognitive
dysfunction
Depression
Genitourinary symptoms
Other 2nd-malignancy
(ie, endometrial cancer)
Chronic fatigue
Cardiovascular effects
Osteoporosis/
bone fractures
Early breast cancer
treatments including:
Radiation therapy
Chemotherapy
Monoclonal antibody
Hormonal therapy
Weight gain

20. Common Symptoms Faced by Breast Cancer
Survivors
 Psycho-neurological cluster: Depressive/anxiety symptoms; Sleep disturbance;
Cognitive changes; Fatigue
20
Treatment Related
Symptom Clusters
Chemotherapy
Induced
Neuropathy
Aromatase
Inhibitor
Arthralgias

21. Mechanistic Biologic Rationale of Symptom
Toxicities
21
Is still missing.
We began to look at chemotherapy effects
in mice and humans to better understand
the role of central inflammation in
symptom cluster as well in chemotherapy
induced neuropathy.
Mouse model of chemotherapyHuman clinical trials; natural history and
Intervention studies

22. Overarching Hypothesis of our group’s
research
Neuroinflammation resulting from chemotherapy administration
promotes:
 Depression
 Anxiety
 Cognitive deficits
 Fatigue.
 Neuropathy
22

23. Chemotherapy induced
neuropathy

24. Chemotherapy induced neuropathy (CIPN)
 Common and can be debilitating
 Associated with a variety of
chemotherapeutic agents
 In breast population: taxanes,
eribulin and platinums
 Impacts ability to give drug, and
has huge impact on function and
quality of life

25. Gaps in Knowledge: CIPN
 How severe are quantitative functional effects of CIPN on gait and
balance in patients undergoing chemotherapy?
 Are early changes in these measures predictors of more severe CIPN
with additional therapy?
 By intervening earlier on functional deficits, can we change the course
of CIPN?
25

26. CIPN Challenges
So common yet so little is known about
*the mechanism of injury
**Who is most at risk
***How to prevent it?
****How to treat it?

28. Summary of preventative strategies for CIPN
There are no agents recommended for the
prevention of CIPN.

30. Summary of therapeutic strategies for CIPN
 Moderate recommendation for use of duloxetine
 Based on limited options that are available for this prominent clinical
problem and the demonstrated efficacy of the following agents in other
neuropathic conditions, it is reasonable to try
*tricyclic antidepressant such as nortriptyline and
amitriptyline
*gabapentin
*A topical agent including baclofen, amitriptyline,
ketamine
 Discuss with patients limited scientific evidence in patients suffering from
CIPN, potential harms and benefits.

32. Duloxetine

34. Sensory Influences on Postural Control
34

35. Balance Testing in Routine Clinic Visits
35
(1) Quiet standing with eyes closed and eyes open for 30 seconds.
(2) Standing reach with dominant foot.
(3) Functional reach with dominant hand.
Evaluate postural stability by measuring center of pressure (CoP) using a force plate

36. Balance Testing in the Lab
Participant walking on treadmill with reflective
markers, and screen shot of motion analysis
software.
Movement
Analysis &
Performance
(MAP) Research
Program’s
Laboratory

37. OSU 13010
 Current NCI R03 (Lustberg, Chaudhari Co-PIs)
 30 breast cancer patients accrued
 Recruited at the time of initiating taxane therapy
 30 additional colon cancer patients initiating oxaliplatin therapy will be
accrued next for comparison

38. 38

39. Self-reported Outcomes
Increasing Motor Complaints
(CIPN20)
Increasing Sensory
Complaints (CIPN20)

40. Quite Standing Balance
40
Increased
Ellipse area
corresponds
to increased
instabilityP<0.001 all time points
0
200
400
600
800
1000
1 2 3 4 5
COP Area
[mm2]
Mean±SE
Timepoint

41. Interim Analysis Results
 For most of these parameters, the significant changes were observed
as early as the 2nd treatment.
 Pain interference from the BPI-SF did not show any significant
changes throughout the study.
 Balance and gait testing are feasible in the clinical setting
 Balance, function and physical functions may all be affected even
without pain symptoms.

42. Next Steps: Future Clinical Trial
Intervene on Early Balance Changes
 Preclinical evidence is emerging that rigorous treadmill exercise
prevents the development of CIPN in a mouse model by reduction of
axonal degeneration.
 Animals undergoing exersise had normal tubulin levels suggesting
that exercise interferes with paclitaxel’s ability to alter microtubule
dynamics in long axons.
 Upregulated BDNF and other neurotropic factors which may also be
beneficial in mitigating CIPN

43. Schema for Proposed Intervention Study

44. Next Steps: Back to the LabWhat is the
Mechanism of Balance Changes?
 Neurotoxicity is impacting peripheral nervous system
 Additional mechanistic information and exact role of central neuro-
inflammation not known
 Role of microglia in spinal cord and brain?
 Contribution of other symptom clusters to neuropathy symptoms and
vice versa
44

45. Conceptual Model of Neuropathy
?
Cancer Treatment
Host Factors

48. Growing a neuron

49. Study Design
 Case controlled study
 20 patients who developed grade 3 CIPN
 20 patients who have no recorded symptoms of CIPN

50. Trial Design
Punch Biopsy Fibroblasts
Differentiate to
Neurons
Evaluate differences in response in
patients who had neuropathy
compared to those that did not
Chemotherapy
Mechanism
Genetic changes
Prevention and
therapeutics.

51. Peripheral neuropathy: what are the central
effects
 Increasing evidence that effects are not all peripheral
 Peripheral neuropathy symptoms after systemic chemotherapy for
breast cancer are associated with changes in cerebral perfusion and
gray matter
 Additional studies are needed for potential diagnostic and
therapeutic implications.

54. Decrease in gray matter density
Less CIPN symptoms
Changes seen in left
cingulate gyrus and right
superior frontal gyrus

55. Chemobrain

56. Chemotherapy and Cognitive Function
 Anthracyclines: [Adriamycin (ADR), Doxorubicin (DOX)] frequently
used treatment in breast cancer patients
 Impact greater than 30% of patients
 Symptoms last 12-24 months in most
 No effective preventative or treatment options

57. Cognitive impairement defined
 Chemobrain is a common term used by cancer survivors to describe
thinking and memory problems that can occur after cancer
treatment.
 Other terms included chemo fog, cognitive changes or cognitive
dysfunction.

58. Memory
Concentration
(Processing time)
Language
(Verbal Fluency
Neurocognitive Changes

59. What patients say about cognitive effects of
chemotherapy:
 “I just don’t feel as sharp as I was before I started my treatment.”
 “I forget things more easily.”
 “I have to work really hard to remember what I did all day.”

60. What patients say….
 I used to run on automatic, now I have to really think and process
things before I do them.
 I find myself checking and re-checking before going through a stop
sign.”
 “It’s a very shaky feeling that makes me unsure of myself.”

61. Factors Affecting Cognitive Functioning
 Age and menopausal status
 Fatigue
 Depression, anxiety, stress
 Pain and pain medications
 Other physical illnesses
 No baseline assessment prechemo
 Above complicates the studies plus biologic mechanism not well-
understood

62. Proposed Mechanisms
 Inflammation
 Oxidative stress
 Neuronal damage

63. Proposed Mechanism: Neuroinflammation and
Oxidative Stress
Block et al. Nature Reviews Neuroscience 8, 57–69 (January 2007) | doi:10.1038/nrn2038
Initial Focus:
microglia
and proinflammatory
cytokines

64. Interactions and Functional Consequences
Chemotherapy Administration
Neuroinflammation
Neuronal Changes
Behavioral Changes
Systemic
Inflammation
Oxidative Stress

65. Chemotherapy Mouse Model
Experimental Design
-1 month
Ovariectomize
CD-1 outbred
female mice
Day 0
Chemo
Day 3
Behavior testing
Cognitive testing
Neuropathy testing

66. Chemotherapy Increases Depressive-like
Behavior in Porsolt Test
Not likely due to fatigue

67. Assessing Cognitive Deficits Using The Barnes Maze:
A Spatial Learning & Memory Task in Rodents
• There is one escape box- the mice are motivated to find it by a dislike of
open spaces
• Important measures
• Latency to enter escape box
• Distance travelled
• Number of Errors
Increased latency and errors are associated with a cognitive deficit.
-1 month
Ovariectomize
CD-1 outbred
female mice
Day 0
Inject mice IV with 45 mg/m2
Doxorubicin + 450 mg/m2
Cyclophosphamide
(approximately 75% of human
equivalent dose)
Day 3-13
Three trials per day
in Barnes Maze

68. Chemotherapy Impairs, But Does Not
Prevent, Learning in the Barnes Maze
*
*
Training Days Reversal Days

69. Increased Proinflammatory Cytokine Expression in
Hippocampus and Cortex is Apparent by 72h

70. Microglial Activation is Apparent by 72h
after Chemotherapy

71. Neuronal Damage
Basal CA1
0
0.5
1
1.5
Vehicle Chemo
SpineDensity/µm *
*
Apical CA3
0
0.5
1
1.5
Vehicle Chemo
SpineDensity/µm
Apical CA1
0
0.4
0.8
1.2
ChemoVehicle
Basal CA3
0
0.5
1
1.5
*
Vehicle Chemo

72. Does a Causal Relationship Exist
Between Neuroinflammation and
Cognitive Deficits?
Minocycline:
In rodents: greater
neuroprotective effect
DoxycyclineTetracyclines
Broad inhibitor of microglial
activation

73. Minocycline Normalizes Pro-inflammatory
Signals
73

74. Minocycline Reduced Cognitive Changes
74

75. Lots to Do…..
 Other agents like Omega 3 supplements– Recent R01
funding to conduct these experiments in mice
 Additional studies investigating CIPN and microglia
peripherally and centrally and whether these are
mitigated by different interventions such as exercise,
minocycline, Omega 3 supplementation
 Additive effects of tumor and chemotherapy on
inflammation
 Social and stress influences on chemo-induced
neuroinflammation and behavioral consequences

76. OSU 13165: Randomized Phase II Study
Chemotherapy: Adrimycin/cytoxan 60 mg/m2/600mg/m2 every 2 weeks x 4 doses
Mincocyline: 100 mg po BID , start 2 weeks prior to chemotherapy and continue for 1 week after chemotherapy
ends.
OSU Pelotonia
Funded Study

77. Neurology. 2009 January 6; 72(1): 56–62.
Microgilia activation
Neuro PET Imaging

78. n-3 PUFA and neuroinflammation
 Reduce markers of oxidative stress
 4- hydroxynonenal (4-HNE), malondialdehyde (MDA)
 Produced when free radicals react with double bonds of
phospholipids -> mitochondrial damage
 Decrease inflammatory cytokines
 TNFα, IL-1β, IL-6
 Decrease post-ischemic/traumatic neuronal damage
 Prevents microglial activation
Eicosapentaenoic acid (EPA); Docosahexaenoic acid (DHA)
DHA is most abundant n-3 PUFA in brain tissue

79. n-3 PUFA and neuroinflammation
Proposed effects of Adriamycin (ADR) and n-3 FAs on TNFα in systemic circulation & brain
Eicosapentaenoic acid (EPA); Docosahexaenoic acid (DHA)
↑4-HNE & MDA
↑SOD
↓4-HNE & MDA

80. n-3 PUFA may preserve cognitive function
 EPA+DHA supplementation/enrichment increases brain tissue EPA+DHA, decreases n-6:n-
3 ratio in rodents
 Short-term feeding of DHA (pre or post injury) enhances cognitive function in rodent
models of traumatic brain injury
 Long-term feeding of EPA+DHA decreases neuronal damage post-ischemic injury in
rodents
 DHA alone or in combination with EPA improves cognitive function (verbal fluency,
recognition and memory) and reduces depression in healthy or mildly cognitively
impaired adults

81. Hypothesis
 A DHA enriched diet will decrease chemotherapy-induced
proinflammatory cytokine expression and markers of oxidative
stress in brain tissue, also decreasing microglial activation, which in
turn will reduce the ADR associated cognitive decline.

82. Study Design
MEG-3 microencapsulated powder added to diet pellets
Human Equivalent Dose Range of ~3.3-6.7 g EPA+DHA/d.
EPA:DHA ratio 1:4

83. Endpoints
 Laboratory measures
 Cognitive function
 Barnes Maze
Brain Assays Blood Assays
Preferred
Sample
Volume to perform in
duplicate
Fatty acids (Gas chromatography) Fatty Acids (Gas chromatography) RBC 100 μL
IL-1beta (Flow cytometry) Corticosterone (RIA) Plasma/Serum 10 μL
TNF alpha (Flow cytometry) C-Reactive Protein (ELISA) Plasma/Serum 10 μL
CD68 (Flow cytometry) MDA (Bioxyteck assay) Plasma/Serum 100 μL
Oxidative stress and antioxidant
defense array
4-HNE (ELISA) Plasma/Serum 200 μL
Cytokine and chemokine array
Dendritic spine density(Dil staining)

84. Significance
 Understanding the mechanisms by which chemotherapy causes
cognitive changes and intervening with DHA to potentially alleviate
these deficits, could vastly improve the quality of life for breast cancer
survivors.
 Additional studies with non pharmacologic interventions are needed
including exercise intervention studies

85. Arthralgias

86. Aromatase Inhibitors
 Three FDA approved drugs: Femara
(anastrazole), Arimidex (anastrazole),
Aromasin (exemestane)
 Improved disease free survival
compared to tamoxifen in
postmenopausal women
 Different side effect profile from
tamoxifen

87. Side-effects of Aromatase Inhibitors
 Hot flashes and other low estrogen symptoms
 Bone loss: recommend regular bone density monitoring
every 2 years while on therapy
 Joint pain
-20-47% of women develop joint symptoms
-Limited treatment options: interruptions in
therapy and nonsteroidal anti-inflammatory drugs
(NSAIDs)
-Not effective in all patients: leads to alteration or
termination of therapy in up to 20% of women.

88. Background: Why?
 Why do arthralgias occur?
 ? Estrogen deprivation directly mediated by AIs is implicated
 Pro-inflammatory cytokines may also be regulated by estrogen

89. Background: Prevention
 Fish and fish oil supplement contain long chain n-3 polyunsaturated
fatty acids (n-3 PUFAs).
 A recent meta-analysis of randomized trials showed reduced joint pain
intensity, morning stiffness, and analgesic use in patients with
rheumatoid arthritis supplemented with these n-3 PUFAs.
 The efficacy of n-3 PUFAs in the prevention of AIIAs was reported as a
feasibility study by our group at the 2014 San Antonio Breast Cancer
symposium:
 Although promising trends were demonstrated by this
investigation, conclusive results were not seen.

90. MRI wrist at baseline and 24 weeks. The axial images
reveal inflammatory induced fluid collections that are more
comprehensibly visualized on the 3D display of the left
wrist volume at both time points. A reduction in
inflammatory changes can be seen.

91. Hypothesis
 Based on observations that n-3 PUFAs have anti-inflammatory effects and
that the mechanism of AIIAs may be in part due to inflammation, we
posit women taking n-3 PUFA supplements will be less likely to develop
AIIAs compared to women on placebo.
 We hypothesize that a woman’s risk for AIIAs and her response to n-3
PUFA supplementation can be predicted by multi-SNP analysis and
modeling.
 This is the first randomized study assessing the efficacy of
preventing AIIAs with n-3 PUFA supplementation while
validating genomic predictors of AI-induced toxicity and
response to therapy.
 Funded by Gateway Foundation

92. Objectives
Objective 1. To determine the efficacy of the complementary
therapy n-3 PUFA supplementation in preventing AIIAs.
Hypothesis. Women receiving n-3 PUFA supplementation will
experience significantly less AIIAs compared to women
receiving placebo.

93. Objectives
Objective 2. To prospectively define the population most at risk for
developing AIIAs by the identification and validation of genetic risk
predictors and to develop an SNP/gene profile predictive of treatment
intervention response.
Hypothesis. In the control group, expanded genomic analysis of germ line
DNA will differentiate patients who develop significant AIIAs from those
patients without symptoms. Among women receiving n-3 PUFA
supplementation, treatment response will be predicted by the
identification of an SNP-based Bayesian network from peripheral blood-
sourced DNA. We further hypothesize that the genes associated with the
SNPs defined in our predictive network will be associated with
inflammatory pathways.

94. Eligibility Criteria
Inclusion criteria
 Women diagnosed with breast cancer stages I-III initiating first line adjuvant AI
therapy with any of the FDA-approved AIs (anastrazole, exemestane, letrozole)
 Concurrent GnRH agonist therapy is allowed. Concurrent breast related
radiation therapy is allowed.
 Prior tamoxifen use is allowed.
 Prior chemotherapy is allowed.
 Age >18 years.
 Ability to understand and the willingness to sign a written informed consent
document.

95. Schema

96. Design
 This is a double-blinded, randomized study of postmenopausal women
with breast cancer stages I-III who are initiating adjuvant endocrine
therapy with FDA approved third generation AIs (letrozole, anastrozole,
or exemestane)
 Enrollment goal: 200 patients with collaboration from The Cleveland
Clinic
 Upon study enrollment, peripheral blood samples will be collected from
these patients in order to obtain genomic DNA.
 Using a fixed-block 1:1 randomization, each subject will then be
randomized to a 6-month treatment period with either oral
administration of n-3 PUFA supplements or a placebo of a mixture of
oils typical of the American diet (TAD) fatty acid ratio.

97. Evaluation
 RBC n-3 PUFAs levels: these are important for capturing long-term (~3
month) n-3 PUFAs intake
 Inflammatory markers: IL-1β, IL-6, IL-17, TNF-RI and TNF-RII
 Arthralgia Assessment: validated instruments that have been used to
evaluate joint symptoms, functional capacity, and quality of life in our
target population.
 Brief Pain Inventory (BPI)
 FACT-B and endocrine subscale (FACT-ES)
 Western Ontario and McMaster Universities Osteoarthritis Index
(WOMAC)
 Modified Score for the Assessment and Quantification of Chronic
Rheumatoid Affections of the Hands (M-SACRAH)

98. Trial to open Summer 2016
 Funding: The Gateway For Cancer Research
 Collaboration with The Cleveland Clinic

101. The Exercise Prescription

102. Leading causes of death
 Heart disease is the #1 killer of women with a history
of breast cancer
91.9
38.6 40.2
21.9
115.6
53.4
36.9 31.1
0
20
40
60
80
100
120
140
CHD STROKE LUNG CANCER BREAST
CANCER
White Women AA Women
Rateper100,000population

103. Cancer treatments can increase the risk of
CHD
 Radiation
 Increases risk of coronary artery disease and myocardial infarction
 Anthracyclines
 Increases risk of heart failure in the subsequent 10 years
 Herceptin (Tratuzumab)
 Increases risk of hypertension or low-normal heart function
 Combination therapy (anthracycline + herceptin)
 Increases risk of heart disease up to 7 times

104. Common risk factors
 Smoking, unhealthy diet, physical inactivity
Breast
Cancer
Cardiovascular
Disease

105. Physical activity reduces mortality among
women
 For each 1-unit ↑ in METs, there is a 17% ↓ risk of death
from all causes
0
1
2
3
4
5
<5 MET 5-8 MET >8 MET
HazardsRatioofDeath
All-Cause
Cardiac
p<0.001

106. Physical activity undertaken after diagnosis
 Physical activity post-diagnoses results in a lower risk of death
Ballard-Barbash et al, JNCI, 2012
Breast cancer mortality All-cause mortality

107. Few women meet physical activity guidelines
 Only 16% of women met physical activity guidelines in 2008
 19% of white women
 11% of black women
 Up to 90% of breast cancer survivors post-treatment do not exercise
regularly
Source: National Health Interview Survey, 2010

108. Existing research on exercise
 Weaknesses of existing exercise studies include a lack of evidence-
based protocol for exercise prescriptions and inconsistent adherence
to the principles of exercise (frequency, intensity, and duration)
 CR is designed to induce changes in the cardiovascular risk profile of
participants
 Includes education on the topics of stress management, smoking cessation,
nutrition, and weight loss
 Exercise prescriptions can be modified for survivors with treatment side-
effects such as lymphedema

109. Cardiac rehabilitation (CR)
 CR programs have substantial extant infrastructure and may improve
morbidity and mortality from both cardiovascular disease and cancer
among breast cancer patients post-treatment
 CR programs, comprising exercise and education, are efficacious in
improving cardiorespiratory fitness, reducing modifiable risk factors,
and improving quality of life (QoL) among high-risk female cardiac
patients
 It remains unknown if a CR program would be efficacious among
lower-risk breast cancer patients

110. Study aims
1. Assess the feasibility of conducting a 14-week CR program in women after
completion of acute therapy for breast cancer
2. Preliminarily evaluate the efficacy of CR in improving cardiorespiratory fitness
(peak oxygen uptake, VO2 max) at 14 weeks.
3. Explore changes in risk factors (blood pressure, cholesterol, fasting glucose,
and body mass index) between baseline and 14-week follow-up.
4. Quantify the difference in QoL between baseline and 14 weeks, adjusting for
baseline QoL values.

111. Study schema
Eligibility
criteria
• Breast cancer patients stages 0-III after
completion of surgery, radiation and/or
chemotherapy
Intervention
• 36-session CR program
• 1-hour sessions, approximately 3x/week for
up to 14 weeks
Analysis
• Feasibility of CR program
• Preliminary assessment of VO2 max, risk
factors, and QoL

112. Inclusion and exclusion
criteria
 Women within 6 months
after completion of all
planned surgery, radiation,
and chemotherapy
 Concurrent endocrine
therapy permissible
 Ages 30-75
 Signed written informed
consent
 Willingness to participate
in CR program
 Metastatic breast cancer
 Other concurrent
malignancies except skin
cancer
 Uncontrolled illness that
would limit compliance
with study requirements
 Pregnant or nursing
women
 Any contraindication to
cardiac stress testing
Inclusion criteria Exclusion criteria

113. Study procedures and process
Graded exercise stress
test
Graded exercise stress
test
Risk factor
assessment
Baseline
assessment
14-week
assessment
Risk factor
assessment
QoL QoL
CR program
36-sessions
(14 weeks)
OSUMC Martha
Morehouse
outpatient CR

114. OSU 14060
 10 out of 20 women currently enrolled
 General satisfaction with program is high
 Logistical issues/barriers to exercise remain for many women

115. Current challenges and future
direction in Oncorehab and breast
cancer survivorship

116. Survivorship Care: Why now?
• Rapidly growing population of survivors
• Promote optimal health for survivors
• Increasing expectations for a better quality of life
• Greater emphasis on patient-centered issues

117. Definition of Cancer Survivor
– Individuals living after (or with) cancer, their families as
well as their care givers, “From the day of diagnosis
through the remainder of their lives”*
– Survivorship as a continuum, integrated into cancer care
*National Coalition for Cancer Survivorship (NCCS) NCI Office of Survivorship, Centers for Disease Control and
Prevention and Lance Armstrong Foundation

118. Institute of Medicine (IOM) 2006:
Lost in Translation
Prevention of recurrent and new
cancer
Management of late effects
Assessment of medical and
psychosocial late effects
Interventions for consequences of
cancer and treatment
Coordination of care among providers

120. Hewitt M, et al. eds. From Cancer Patient to Cancer Survivor: Lost in Transition.
Washington DC; The National Academies Press; 2005.
Essential Components of Follow-up Care of a Breast
Cancer Patient
Treating the consequences
of cancer and its
treatments
New cancers,
recurrence, late
effects
Recurrence, second cancers,
and assessing medical and
psychosocial late effects
Interdisciplinary
coordination between
PCPs and specialists

122. Distress Assessment: James Supportive Care
Screening Tool
 Use of the James Supportive Care Screening (SCS):
 A patient self-report instrument designed to
capture the most common symptoms reported
by cancer survivors
 When combined with targeted referrals, our
tool will allow cancer programs to meet:
 The screening standards of the NCCN
 ACS Accreditation Standards

123. James Supportive Care Screening Tool

125. Goals
 100% of all nonmetastatic cancer patietns will have a survivorship
care plan
 100% will have distress screening
 Currently at 60-70% at the Stefanie Spielman Breast Center

126. Rehabilitation Needs of Breast Cancer
Survivors
 We oncologists cannot do this alone
 Many challenges
 Many opportunities
 Landscape will be changed in the next decade

131. More research is needed
 Understand the biological basis of the symptoms patients experience as a
consequence of treatment
 Evidence based approaches on how to best intervene
 How to coordinate care and referrals
 How to individualize care for reach patient, survivor, thriver

132. Vision
Develop a program project grant in neurological complications of cancer treatment
Biologic Basis of Chemo Brain
And treatment /preventative
strategies
Novel neuroimaging of treatment
induced toxicities
Upcoming steps: apply for Pelotonia Team Award
*Neuro-Imaging; expand R01 funding
Chemotherapy induced neuropathy
Ajit Chaudhari
Mechanical Engineering
Health and Rehab Sciences
Courtney DeVries
Neuroscience
Maryam Lustberg
Medical Oncology
Fen Xia
Radiation Oncology
Brian Focht
Kinesiology
Michael Knopp
Wright Center
Ali Rezai
Center for Neuroscience

133.  DeVries Laboratory
 Chaudhari Laboratory
 Michael Knopp
 Rebecca Andridge
 Rebecca Jackson
 Charles Shapiro
 Janice Kiekolt-Glaser
 SSCBC Breast medical oncology
colleagues
 Patients and families
 CCTS funding
 Pelotonia funding (Idea Award
2012)
 Spielman Fund
 NCI: R01CA189947
R01CA194924
R03CA182165
Acknowledgements

134. Thank You
134