Pain definition: “An unpleasant sensory and emotional experience associated with actual or potential tissue injury or described in terms of such damage.”
(International Association for the Study of Pain
Figure 1. Pain and the quality of life (Qol)
Definitions(6):
AI Arthralgia (AIA) = joints pain/stiffness NOT caused by arthritis
AI-induced musculoskeletal syndrome (AIMSS) = arthralgia or joint pain + musculoskeletal pain + carpal tunnel syndrome + joint stiffness + paresthesia
Aromatase Inhibitors Arthralgia (AIA)(1,2,5) Major criteria:
Currently taking aromatase inhibitors (AI)
Joint pain which has developed or worsened since starting AI
Joint pain improves or resolves within 2 weeks of stopping AI
Joint pain returns upon resuming AI.
Minor criteria:
Symmetrical joint pains
Pain in hands and/or wrists
Carpal tunnel syndrome
Decreased grip strength
Morning stiffness
Improvement in joint discomfort with use or exercise
Diagnosis: all of the following major criteria, and at least three minor criteria
44-47% women - joint pain and stiffness
20-50% women - arthralgia
Joint symptoms most often develop within the first 3 months on therapy and peak at 6 months
Typically affect the fingers, hands, wrists, elbows, shoulders, knees and ankles.
Figure 2. Occurence of 5 types of pain syndrome over the 1-year study period. The data shown for each visit are the numbers of patients developing a specific pain syndrome
AIA complications
Pain → discontinuation of AI in up to 20% of patients.
AIA treatment(1,3-5,9-11,13)
AIA complications
Pain → discontinuation of AI in up to 20% of patients.
AIA treatment(1,3-5,9-11,13)
n Definitive therapy for AI-induced arthralgias has not been developed.
1) Patient education
patients uncertain which healthcare professional address the AIs side effects.
advise patients: AIA is common; can be managed by drug therapy and lifestyle changes
⇒ Adherence to AI therapy.
2) Pain assessment
Women on AI should undergo pain assessments for at least 1 year.
Yoga may be effective; needs verification in further trials.
Acupuncture may reduce pain from joint symptoms and improve functioning and well-being.
4) Calcium and vitamin D supplements
n Vitamin D levels should be measured routinely and optimized throughout the patient,s lifetime.
n Women,s Health Initiative Observational Study:
31% increased risk of fracture in women with vs. those without breast cancer
5-fold increased risk of vertebral compression fractures in women with breast cancer with or without bony metastases.
5) Omega-3 fatty acids
Anti-inflammatory effects
Placebo-controlled trial:
3.3 g Omega-3-fatty acids, 249 women on AIs with severe pain (≥5/10) and/or stiffness
60% improvement observed in the group randomized to Omega-3
similar reduction was seen in the placebo (soybean/corn oil) arm.
6) Pharmacologic
NSAIDs (ibuprofen) or a COX2 inhibitor - recommended as first-line treatment
APAP
Anticonvulsants: gabapentin, pregabalin
Opioids
Duloxetine:
single-arm, open-label phase 2 study:
29 women with breast cancer with new or worsening pain with AI
21 women (72.4%) achieved at least 30% decrease in average pain
Bisphosphonates:
May prevent AI-related joint symptoms
ASCO recommends bisphosphonate therapy for all women undergoing adjuvant therapy for breast cancer with T score <-2.5
Prednisolone, short course, low-dose:
small, non-randomized trial of 27 patients
5 mg of prednisolone daily for 1 week
67% of patients reported immediate relief in joint pain
63% still reporting improvement at 1 month
Consider switching to tamoxifen if symptoms cannot be managed - Tamoxifen + Cymbalta (CYP2D6)!
Stop therapy for 6 to 8 weeks to ensure the AI is the cause of the symptoms prior to switching.
Figure 3. Pharmacologic options for the amelioration of pain in early breast cancer patients with symptoms of athralgia
Figure 3. Pharmacologic options for the amelioration of pain in early breast cancer patients with symptoms of athralgia
Figure 4. Potential interventions for athralgia
Figure 5. Potential treatments for myalgias and arthralgias caused by cancer
Figure 6. The management of arthralgias in cancer patients
Bibliografie
1. J. Files, M. Ko, S. Pruthi - Managing Aromatase Inhibitors in Breast Cancer Survivors: Not Just for Oncologists - Mayo Clinical Proceedings, 2010 Jun; 85(6): 560–566.
2. C. Thorne - Management of arthralgias associated with aromatase inhibitor therapy, Current Oncology, 2007 Dec; 14(Suppl 1): S11–S19.
3. OncoLink, Penn Medicine, last modified: September 29, 2016.
4. F. Laroche, J. Coste, T. Medkour, PH Cottu, JY Pierga, JP Lotz, K. Beerblock, et al. - Classification of and Risk Factors for Estrogen Deprivation Pain Syndromes Related to Aromatase Inhibitor Treatments in Women With Breast Cancer: A Prospective Multicenter Cohort Study - The Journal of Pain, Vol 15, No 3 (March), 2014: pp 293-303.
5. P. Niravath - Aromatase inhibitor-induced arthralgia: a review, Annals of Oncology (2013) 24 (6): 1443-1449.
6. A. Lintermans, P. Neven - Pharmacology of arthralgia with estrogen deprivation, Steroids, 2011 Jul;76(8):781-5.
7. D. Wendling, H. Letho-Gyselinck, X. Guillot, C. Prati, X. Pivot - Arthralgia and aromatase inhibitors, Joint Bone spine, 2014 Mar;81(2):187-8.
8. HJ Burstein - Aromatase inhibitor-associated arthralgia syndrome, The Breast, vol. 16, Issue3, June 2007, Pages 223–234.
9. RE Coleman, WW Bolten, M Lansdown, S Dale, C Jackisch, D Merkel, N Maass, P Hadji - Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations, Cancer Treatment Reviews, 2008 May;34(3):275-82.
10. C Yeh, W Lin, L Wood, D Bovbjerg, G van Londen - Auricular point acupressure to manage aromatase inhibitor-induced arthralgia in postmenopausal breast cancer survivors, Journal of pain 2016 Apr;17(4S):S114.
11. K Bae, HS Yoo, G Lamoury, F Boyle, DS Rosenthal, B Oh - Acupuncture for Aromatase Inhibitor-Induced Arthralgia: A Systematic Review, Integrative Cancer Therapeutics, 2015 Nov;14(6):496-502.
12. J Younus, L Kligman. Management of aromatase inhibitor–induced arthralgia, Current Oncology, 2010 Feb; 17(1): 87–90,PMCID: PMC2826784.
13. DL Hershman, C Loprinzi, BP Schneider- Symptoms: Aromatase Inhibitor Induced Arthralgias, Advances in Experimental Medicine and Biology, 2015;862:89-100.
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