Musculoskeletal issues in breast cancer - Sasha E. Knowlton, MD Assistant Director of Cancer Rehabilitation - Mass General Hospital
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Musculoskeletal issues in breast cancer
Your
Sashaname and credentials
E. Knowlton, MD
Assistant Director of Cancer Rehabilitation
Disclosures • I have no financial relationships with a commercial entity producing healthcare-related products and/or services to disclose.
Outline of talk • General information • Anatomy review • Impairments – Shoulder – Neck – Nerves – Pain – Others
The Past
• Egyptians through Hippocrates
• 1900s: Halsted radical mastectomy
• Further surgeries
• 1930s-1940s: Chemotherapy+Radiation Image:
http://www.amazon.com/Bathshebas-
Breast-Women-Cancer-
History/dp/0801880645
• 1970s: Mammograms and hormone therapy
Mandell, Jessica B. "Bathsheba’s breast Women, cancer & history." Journal of Clinical Investigation 115.6 (2005): 1397.
Who are we talking about? Figure 1 from: Siegel, Rebecca, et al. "Cancer treatment and survivorship statistics, 2012."CA: a cancer journal for clinicians 62.4 (2012): 220-241. Siegel, Rebecca, Deepa Naishadham, and Ahmedin Jemal. "Cancer statistics, 2013." CA: a cancer journal for clinicians 63.1 (2013): 11-30.
Examples of Cancer-related
Impairments
• Fatigue • Lumbosacral plexopathy
• Arthralgia • Neck pain
• Myalgia • Osteopenia/osteoporosis
• Neuropathic pain • Paralysis
• Weakness • Radiation Fibrosis Syndrome
• Deconditioning • Radiculopathy
• Autonomic dysfunction • Scapular winging
• Back pain • Scar adhesions
• Balance dysfunction • Sensory deficits
• Bowel dysfunction • Sexual dysfunction
• Chemotherapy-induced peripheral • Shoulder pain
neuropathy • Dysphagia
• Dystonia • Trismus
• Graft-versus-host-disease • Urinary dysfunction
• Headaches • Muscular asymmetry
• Falls • Visuospatial dysfunction
Silver, Julie K., Jennifer Baima, and R. Samuel Mayer. "Impairment‐driven cancer rehabilitation: An essential component of quality
care and survivorship."CA: a cancer journal for clinicians 63.5 (2013): 295-317.
How common are
impairments in breast cancer?
• In one study, 6 years after
diagnosis, >60% of women
experienced at least one
impairment
• In another study of
metastatic breast cancer
patients, 92% identified at
least one impairment
Figure 1 from: Cheville, Andrea L., et al. "Prevalence and treatment
Schmitz, Kathryn H., et al. "Prevalence of breast cancer treatment sequelae over 6 patterns of physical impairments in patients with metastatic breast
years of follow‐up." Cancer 118.S8 (2012): 2217-2225. cancer." Journal of Clinical Oncology 26.16 (2008): 2621-2629.
Cheville, Andrea L., et al. "Prevalence and treatment patterns of physical
impairments in patients with metastatic breast cancer." Journal of Clinical Oncology
26.16 (2008): 2621-2629.
What is it? “Cancer rehabilitation involves helping a person with cancer to help himself or herself to attain maximum physical, social, psychological and vocational functioning within the limits imposed by the disease and its treatment” Cromes 1978 “Cancer rehabilitation is a program that helps people with cancer to maintain and restore physical and emotional well-being. Cancer rehabilitation is available before, during and after cancer treatment.” Mayo Clinic 2012 Cromes Jr, G. Fred. "Implementation of Interdisciplinary Cancer Rehabilitation." Rehabilitation Counseling Bulletin 21.3 (1978): 230-7. Mayo Clinic Staff. Tests and Procedures: Cancer rehabilitation in Minnesota. http://www.mayoclinic.org/tests-procedures/cancer-rehabilitation/basics/definition/prc-20020133
Overview of breast cancer
interventions
• Partial mastectomy (i.e.
lumpectomy)
• Mastectomy
– Simple
– Skin-sparing (or nipple sparing)
– Modified radical
– Radical
• Lymph node dissection
– Axillary versus Sentinel
• Radiation/Chemotherapy http://www.cancer.org/cancer/breastcancer/detailedguide/breast-
cancer-treating-surgery
Anatomy Review - Chest https://plus.google.com/+ammedicine/posts/UiZJzT8ZYkS#+ammedici http://rakdojke.kbsplit.hr/images/fig10.jpg ne/posts/UiZJzT8ZYkS
Anatomy Review - Shoulder Posterior shoulder Anterior Shoulder http://www.iaeeperth2012.org/recommendations-on-netter-atlas-of- human-anatomy/anatomy-of-the-shoulder-joint-human-atlas-of-anatomy- https://www.pinterest.com/pin/494833077782501164/ netter/
Anatomy Review - Neck
http://www.suggestkeyword.com/c2hvdWxkZXIgbXVzY2xlcw/Why should we be concerned about musculoskeletal issues in breast cancer? • High prevalence of arm/shoulder problems in breast cancer survivors • Nesvold (2011) investigated breast cancer survivors (stage II –III) between 4-7 years after diagnosis • All had modified radical mastectomy or lumpectomy with axillary lymph node dissection with radiation (50 Gy in 25 fractions) • Women who had arm/shoulder problems reported lower quality of life scores which did not change significantly 3 years later Nesvold, Inger-Lise, et al. "The relation between arm/shoulder problems and quality of life in breast cancer survivors: a cross-sectional and longitudinal study." Journal of Cancer Survivorship 5.1 (2011): 62-72. Yang, Eun Joo, et al. "Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study." Journal of surgical oncology 101.1 (2010): 84.
The Need for Cancer Rehab Services • Cheville et al: 163 patients with stage IV breast cancer Figure 1 from: Cheville, Andrea L., Alice B. Kornblith, and Jeffrey R. Basford. "An examination of the causes for the underutilization of rehabilitation services among people with advanced cancer." American Journal of Physical Medicine & Rehabilitation 90.5 (2011): S27-S37.
Part I: Shoulder
How do breast cancer survivors compare to those
who have not had breast cancer?
• Diagnosed with stage 0-III breast cancer and completed all
treatment within 6 months
• Compared to similar women:
– Decreased shoulder strength
– Decreased active and passive range of motion
– Increased shoulder disability
Harrington, Shana, et al. "Comparison of shoulder flexibility, strength, and function between breast cancer survivors and healthy participants."
Journal of Cancer Survivorship 5.2 (2011): 167-174.Rotator Cuff
• Symptoms include
– Pain
– Limited movement*
– Weakness*
– Reduced function
• Treatment
– Physical therapy
– Medications
– Injections
https://www.nlm.nih.gov/medlineplus/ency/imagepages/19622.htm
Ebaugh, David, Bryan Spinelli, and Kathryn H. Schmitz. "Shoulder impairments and their association with symptomatic rotator cuff disease in
breast cancer survivors." Medical hypotheses 77.4 (2011): 481-487.Adhesive Capsulitis
• AKA “Frozen Shoulder”
• Symptoms
– Pain
– Reduced movement
• Treatment
– Physical therapy
– Medications
http://www.kleisertherapy.com/adhesive-capsulitis-frozen-shoulder/Axillary Web Syndrome
• Aka “Cording”
• Painful palpable cords of
fibrous tissue that develop
post-operatively and limit
movement
• Incidence 12 months post-
operatively: 28-48% http://klosetraining.com/course/in-classroom/breast-cancer-
rehabilitation/
http://www.breastcancer.org/treatment/side_effects/aws
Lacomba, María Torres, et al. "Axillary web syndrome after axillary dissection in breast cancer: a prospective study." Breast cancer research and treatment 117.3 (2009): 625-
630.
Bergmann, Anke, et al. "Incidence and risk factors for axillary web syndrome after breast cancer surgery." Breast cancer research and treatment 131.3 (2012): 987-992.
Lacomba, María Torres, et al. "Incidence of myofascial pain syndrome in breast cancer surgery: a prospective study." The Clinical journal of pain 26.4 (2010): 320-325.Aromatase Inhibitor-Induced
Arthralgia
• Aromatase Inhibitors (AI)
– Anastrozole
– Letrozole
– Exemestane
• Arthralgia includes:
– Symmetric joint pains
– Carpal tunnel syndrome
– Trigger finger
• Boonstra et al:
– Incidence 74% Figure 1 from Niravath, P. "Aromatase inhibitor-induced arthralgia: a review."
Annals of oncology 24.6 (2013): 1443-1449
Niravath, P. "Aromatase inhibitor-induced arthralgia: a review." Annals of oncology 24.6 (2013): 1443-1449.
Boonstra, Amilie, et al. "Arthralgia during aromatase inhibitor treatment in early breast cancer patients: prevalence, impact, and recognition by healthcare providers." Cancer
nursing 36.1 (2013): 52-59.
Gaillard, Stéphanie, and Vered Stearns. "Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management."
Breast Cancer Res 13.2 (2011): 205.Management of AI-induced
arthralgia
• Non-pharmacologic
– HOPE trial
• Pain management
– Psychological treatments
– NSAIDs or Tylenol
– Narcotics
• Briot et al: The ATOLL study
– Switching to a different aromatase inhibitor agent
• Overall needs more investigation
• Irwin M et al. Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Onc 33(10). 2015. 1104-1111.
• Janni, Wolfgang, and Philip Hepp. "Adjuvant aromatase inhibitor therapy: outcomes and safety." Cancer treatment reviews 36.3 (2010): 249-261.
• Briot, Karine, et al. "Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer:
the ATOLL (articular tolerance of letrozole) study." Breast cancer research and treatment 120.1 (2010): 127-134.
• Renshaw, L., et al. "Comparison of joint problems as reported by patients in a randomised adjuvant trial of anastrozole and letrozole." Breast Cancer Research and
Treatment. Vol. 106. 233 SPRING STREET, NEW YORK, NY 10013 USA: SPRINGER, 2007.
• Roberts K et al. Management of aromatase inhibitor induced musculoskeltal symptoms in postmenopausal early breast cancer: A systematic review and metanalysis.
Critical Reviews in Oncology/Hematology. 2017. 111:66-80.Part II: Neck
Cervical Radiculopathy
• Symptoms include
– Neck and arm pain
– Numbness
– Weakness
• Additional testing if worsening
symptoms
• Treatment
– Medications
– Physical/Occupational Therapy
– Injections http://www.advancedspineboston.com/conditions/cervical-
radiculopathy/
– Surgery
Stubblefield, Michael D., and Nandita Keole. "Upper body pain and functional disorders in patients with breast cancer." PM&R 6.2 (2014): 170-
183.Myofascial pain syndrome
• Syndrome of active
myofascial trigger points
• Incidence 12 months after
surgery: 44.8%
– Commonly in lattisimus dorsi,
serratus anterior, pectoralis
major
• Not influenced by surgery, http://www.fysioteam-hilversum.nl/behandelingen/triggerpoint-
radiation, number of lymph therapie/
nodes removed
Lacomba, María Torres, et al. "Incidence of myofascial pain syndrome in breast cancer surgery: a prospective study." The Clinical journal of pain
26.4 (2010): 320-325.Part III: Nerves
Brachial Plexopathy
• Possible cancer-related causes
– Radiation
– Recurrence/Metastases
• Symptoms
– Pain
– Sensation changes
– Weakness
• Treatment based on cause
http://www.assh.org/handcare/hand-arm-injuries/Brachial-Plexus-
Injury#prettyPhoto[Gallery 3977_38203]/0/
Stubblefield, Michael D., and Nandita Keole. "Upper body pain and functional disorders in patients with breast cancer." PM&R 6.2 (2014): 170-
183.Chemotherapy Induced
Peripheral Neuropathy
• Results from damage or
dysfunction of peripheral
nerves
– Sensory
– Motor
– Autonomic
• Review by Seretny et al:
– 68.1% prevalence of CIPN
within 1st month
– 60% at 3 months
Figure 1 from: Han, Yaqin, and Maree T. Smith. "Pathobiology of
– 30% at 6 months or more cancer chemotherapy-induced peripheral neuropathy
(CIPN)." Frontiers in pharmacology 4 (2013).
Stubblefield, Michael D., et al. "A prospective surveillance model for physical rehabilitation of women with breast
cancer." Cancer 118.S8 (2012): 2250-2260.
Seretny, Marta, et al. "Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review
and meta-analysis."PAIN® 155.12 (2014): 2461-2470.Why care about CIPN?
• Quality of life
– Tofthagen et al: Worse quality of life associated
with increased CIPN
– Mols et al: CIPN and quality of life systematic
review
• Majority of studies show more CIPN
symptoms correlated with lower quality of
life
• Tofthagen, Cindy, et al. "Oxaliplatin-induced peripheral neuropathy’s effects on health-related quality of life of colorectal cancer
survivors." Supportive Care in Cancer 21.12 (2013): 3307-3313.
• Mols, Floortje, et al. "Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review." Supportive Care
in Cancer22.8 (2014): 2261-2269.Why care about CIPN?
• Worse performance on functional
tests
• Conservative gait with slowed
walking speed = increased fall risk
• Lower levels of function/ADLs
• Increased odds of falling x 1.8
• Winters-Stone KM et al. Falls, functioning and disability among women with persistent symptoms of chemotherapy-induced peripheral
neuropathy. J Clin Oncology. 35(23). 2017. 2604-2610.CIPN: Prevention and
Treatment
• Hershman et al: Practice Guideline
– No agents for prevention
– Duloxetine can be used for treatment
• PT - desensitization, proprioceptive feedback,
TENS
• AFOs
• Others – acupuncture
• Smith, Ellen M. Lavoie, et al. "Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful
peripheral neuropathy: a randomized clinical trial." Jama 309.13 (2013): 1359-1367.
• Argyriou, Andreas A., et al. "Chemotherapy-induced peripheral neurotoxicity (CIPN): an update." Critical reviews in oncology/hematology 82.1
(2012): 51-77.
• Hershman, Dawn L., et al. "Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American
Society of Clinical Oncology clinical practice guideline." Journal of Clinical Oncology(2014): JCO-2013.
• Kleckner IR et al. Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomizedMononeuropathy
• Types
– Carpal tunnel syndrome
– Ulnar mononeuropathy
• Testing
– Electrodiagnostics
• Treatment
– Splints
– Physical+occupational therapy http://www.wecareforlife.com/hand-
center/endoscopiccarpaltunnelrelease
– Medications
– Injections
– Surgical release
Stubblefield, Michael D., and Nandita Keole. "Upper body pain and functional disorders in patients with breast cancer." PM&R 6.2 (2014): 170-
183.Part IV: Post-mastectomy Pain Syndrome http://image.slidesharecdn.com/axillabrachialplexus-150228083159-conversion-gate02/95/axilla-brachial-plexus-14-638.jpg?cb=1425120668
Proposed 2016 definition • Post-mastectomy pain syndrome: • Occurs after any breast surgery • At least moderate severity • Possesses neuropathic qualities • Located in the ipsilateral breast/chest wall, axilla, and/or arm • Lasts at least 6 months • Occurs at least 50% of the time • May be exacerbated by movements of the shoulder girdle. Waltho D and Rockwell G. Post-breast surgery pain syndrome: establishing a consensus for the definition of post-mastectomy pain syndrome to provide a standardized clinical and research approach – a review of the literature and discussion. J can chir. 2016. 59(5): 342- 350.
Management of PMPS
• Medications
• Gabapentin
• Venlafaxine/Duloxetine
• TCAs: amitriptyline, imipramine, doxepin, nortriptyline
• Topicals (lidocaine, capsaicin)
• Nerve Blocks
• Rehabilitation
• Resection of neuroma
• Tinel’s sign followed by lidocaine block
• Alternative medicine
• Counseling
• Wisotzky E et al. Deconstructing Postmastectomy Syndrome: Implications for Physiatric Management. Phys Med Rehabil Clin N Am. 28.
2017. 153-169
• UpToDate: Postmastectomy pain syndrome: Risk reduction and management
• Amichetti M and O Caffo. Pain after quadrantectomy and radiotherapy for early-stage breast cancer: Incidence, characteristics and
influence of quality of life. Oncology 2003. 65:23-28.Part V: Other
Lymphedema
• Accumulation of fluid
• Limits motion; pain,
heaviness, numbness
• Treatments include
– Physical therapy
– Medications
– Surgery/lasers
http://www.womenshealthsection.com/content/gyno/gyno005.php3
Stubblefield, Michael D., and Nandita Keole. "Upper body pain and functional disorders in patients with breast cancer." PM&R 6.2 (2014): 170-
183.
Taghian, Nadine R., et al. "Lymphedema following breast cancer treatment and impact on quality of life: A review." Critical reviews in
oncology/hematology 92.3 (2014): 227-234.
Harris, Susan R., et al. "Clinical practice guidelines for breast cancer rehabilitation." Cancer 118.S8 (2012): 2312-2324.Are there any guidelines?
• Clinical practice guideline published 2012
– Preoperative arm function assessment
– Postoperative physical therapy
– Active stretching
– Frequent reassessments
– Progressive resistance exercises
• Other guidelines for cancer-related pain, fatigue,
peripheral neuropathy
Harris, Susan R., et al. "Clinical practice guidelines for breast cancer rehabilitation." Cancer 118.S8 (2012): 2312-2324.QUESTIONS?
References http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-treating-surgery Stubblefield, Michael D., and Nandita Keole. "Upper body pain and functional disorders in patients with breast cancer." PM&R 6.2 (2014): 170-183. Mandell, Jessica B. "Bathsheba’s breast Women, cancer & history." Journal of Clinical Investigation 115.6 (2005): 1397. Siegel, Rebecca, Deepa Naishadham, and Ahmedin Jemal. "Cancer statistics, 2013." CA: a cancer journal for clinicians 63.1 (2013): 11-30. Silver, Julie K., Jennifer Baima, and R. Samuel Mayer. "Impairment‐driven cancer rehabilitation: An essential component of quality care and survivorship."CA: a cancer journal for clinicians 63.5 (2013): 295-317. Schmitz, Kathryn H., et al. "Prevalence of breast cancer treatment sequelae over 6 years of follow‐up." Cancer 118.S8 (2012): 2217-2225. Cheville, Andrea L., et al. "Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer." Journal of Clinical Oncology 26.16 (2008): 2621-2629. Nesvold, Inger-Lise, et al. "The relation between arm/shoulder problems and quality of life in breast cancer survivors: a cross-sectional and longitudinal study." Journal of Cancer Survivorship 5.1 (2011): 62-72. Yang, Eun Joo, et al. "Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study." Journal of surgical oncology 101.1 (2010): 84. Harrington, Shana, et al. "Comparison of shoulder flexibility, strength, and function between breast cancer survivors and healthy participants." Journal of Cancer Survivorship 5.2 (2011): 167-174. Ebaugh, David, Bryan Spinelli, and Kathryn H. Schmitz. "Shoulder impairments and their association with symptomatic rotator cuff disease in breast cancer survivors." Medical hypotheses 77.4 (2011): 481-487. http://www.breastcancer.org/treatment/side_effects/aws Lacomba, María Torres, et al. "Axillary web syndrome after axillary dissection in breast cancer: a prospective study." Breast cancer research and treatment 117.3 (2009): 625-630. Bergmann, Anke, et al. "Incidence and risk factors for axillary web syndrome after breast cancer surgery." Breast cancer research and treatment 131.3 (2012): 987-992. Lacomba, María Torres, et al. "Incidence of myofascial pain syndrome in breast cancer surgery: a prospective study." The Clinical journal of pain 26.4 (2010): 320-325. Niravath, P. "Aromatase inhibitor-induced arthralgia: a review." Annals of oncology 24.6 (2013): 1443-1449. Boonstra, Amilie, et al. "Arthralgia during aromatase inhibitor treatment in early breast cancer patients: prevalence, impact, and recognition by healthcare providers." Cancer nursing 36.1 (2013): 52-59. Gaillard, Stéphanie, and Vered Stearns. "Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management." Breast Cancer Res 13.2 (2011): 205. Briot, Karine, et al. "Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study." Breast cancer research and treatment 120.1 (2010): 127-134. Renshaw, L., et al. "Comparison of joint problems as reported by patients in a randomised adjuvant trial of anastrozole and letrozole." Breast Cancer Research and Treatment. Vol. 106. 233 SPRING STREET, NEW YORK, NY 10013 USA: SPRINGER, 2007. Janni, Wolfgang, and Philip Hepp. "Adjuvant aromatase inhibitor therapy: outcomes and safety." Cancer treatment reviews 36.3 (2010): 249-261. Stubblefield, Michael D., and Nandita Keole. "Upper body pain and functional disorders in patients with breast cancer." PM&R 6.2 (2014): 170-183. Lacomba, María Torres, et al. "Incidence of myofascial pain syndrome in breast cancer surgery: a prospective study." The Clinical journal of pain 26.4 (2010): 320-325. Lacomba, María Torres, et al. "Incidence of myofascial pain syndrome in breast cancer surgery: a prospective study." The Clinical journal of pain 26.4 (2010): 320-325. Stubblefield, Michael D., et al. "A prospective surveillance model for physical rehabilitation of women with breast cancer." Cancer 118.S8 (2012): 2250-2260. Seretny, Marta, et al. "Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis."PAIN® 155.12 (2014): 2461-2470. Taghian, Nadine R., et al. "Lymphedema following breast cancer treatment and impact on quality of life: A review." Critical reviews in oncology/hematology 92.3 (2014): 227-234. Harris, Susan R., et al. "Clinical practice guidelines for breast cancer rehabilitation." Cancer 118.S8 (2012): 2312-2324. Harris, Susan R., et al. "Clinical practice guidelines for breast cancer rehabilitation." Cancer 118.S8 (2012): 2312-2324.
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