Abstract
Chronic pain after breast cancer treatment is a major clinical problem, affecting
25 to 60% of patients. Development of chronic pain after breast cancer treatment,
as well as other surgical procedures, involves a complex pathophysiology that involves
pre-, intra- and post-operative factors. This review is a systematic analysis on methodology
and evidence in research into persistent pain after breast cancer treatment during
the period 1995 to 2010, in order to clarify the significance and relative role of
potential risk factors. Literature was identified by a search in PubMed and OVID,
as well as by obtaining relevant studies from a systematic review of reference lists.
Sixty papers were identified, most of these being retrospective or questionnaires.
Only 2 studies included quantitative sensory testing and only 26 studies were prospective.
Furthermore, about a third of the studies did not apply modern principles of surgical
and adjuvant therapy. In summary, the data show inconsistencies in definition of chronic
pain and treatment groups, as well as in the collection of pre- intra- and post-operative
data, precluding conclusions with regard to pathophysiologic mechanisms as well as
rational strategies for prevention and treatment. However, nerve damage and radiotherapy
appear to be significant risk factors for chronic pain. A proposal for the design
of future prospective studies is presented.
Perspective
A comprehensive and systematic approach to research in chronic pain after breast cancer
treatment is necessary in order to understand the pathophysiology and thus develop
strategies for prevention and treatment.
Key words
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References
- Chronic postoperative pain: The case of inguinal herniorrhaphy.Br J Anaesth. 2005; 95: 69-76
- Predictive risk factors for persistent postherniotomy pain.Anesthesiology. 2010; 112: 957-969
- Prospective randomized controlled trial of preservation of the intercostobrachial nerve during axillary node clearance for breast cancer.Br J Surg. 1998; 85: 1443-1445
- Pain after quadrantectomy and radiotherapy for early-stage breast cancer: Incidence, characteristics and influence on quality of life. Results from a retrospective study.Oncology. 2003; 65: 23-28
- Depression and pain comorbidity: A literature review.Arch Intern Med. 2003; 163: 2433-2445
- Is there a life-long risk of brachial plexopathy after radiotherapy of supraclavicular lymph nodes in breast cancer patients?.Radiother Oncol. 2004; 71: 297-301
- Subjective morbidity and quality of life after sentinel node biopsy and axillary lymph node dissection for breast cancer.J Surg Oncol. 2005; 92: 17-22
- Some cases of severe post-mastectomy pain syndrome may be caused by an axillary haematoma.Pain. 2004; 108: 294-296
- Risk factors for chronic pain after hysterectomy: A nationwide questionnaire and database study.Anesthesiology. 2007; 106: 1003-1012
- Preventive analgesia to reduce wound hyperalgesia and persistent postsurgical pain: Not an easy path.Anesthesiology. 2005; 103: 681-683
- Pain and quality of life after surgery for breast cancer.Breast Cancer Res Treat. 2003; 80: 39-48
- Mind-body interactions in pain: The neurophysiology of anxious and catastrophic pain-related thoughts.Transl Res. 2009; 153: 97-101
- Postmastectomy/postlumpectomy pain in breast cancer survivors.J Clin Epidemiol. 1998; 51: 1285-1292
- Risk factors for pain after mastectomy/lumpectomy.Cancer Pract. 1999; 7: 66-70
- Aromatase inhibitor-induced arthralgia: Clinical experience and treatment recommendations.Cancer Treat Rev. 2008; 34: 275-282
- Outcome of patients with severe chronic pain following repair of groin hernia.Br J Surg. 2002; 89: 1310-1314
- Neurologic complications of radiation therapy.Neurol Clin. 2003; 21: 249-277
- Anatomical variants of the intercostobrachial nerve encountered during axillary dissection.Breast. 2001; 10: 160-162
- Morbidity comparison of sentinel lymph node biopsy versus conventional axillary lymph node dissection for breast cancer patients: Results of the sentinella-GIVOM Italian randomised clinical trial.Eur J Surg Oncol. 2008; 34: 508-513
- Genetic architecture of human pain perception.Trends Genet. 2007; 23: 605-613
- Core outcome measures for chronic pain clinical trials: IMMPACT recommendations.Pain. 2005; 113: 9-19
- Effect of early administration of the N-methyl-d-aspartate receptor antagonist amantadine on the development of postmastectomy pain syndrome: A prospective pilot study.J Pain. 2007; 8: 223-229
- Early and late morbidity associated with axillary levels I-III dissection in breast cancer.J Surg Oncol. 2002; 79: 151-155
- The analgesic effect of gabapentin and mexiletine after breast surgery for cancer.Anesth Analg. 2002; 95 (table): 985-991
- EMLA reduces acute and chronic pain after breast surgery for cancer.Reg Anesth Pain Med. 2000; 25: 350-355
- Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer.Anesth. Analg. 2005; 101: 1427-1432
- Acute and persistent postoperative pain after breast surgery.Pain Med. 2009; 10: 708-715
- Long term results of a randomised prospective study of preservation of the intercostobrachial nerve.Eur J Surg Oncol. 2003; 29: 213-215
- Self-reported arm-lymphedema and functional impairment after breast cancer treatment–A nationwide study of prevalence and associated factors.Breast. 2010; 19: 506-515
- Prevalence of and factors associated with persistent pain following breast cancer surgery.JAMA. 2009; 302: 1985-1992
- Age-related differences in pain perception and report.Clin Geriatr Med. 2001; 17: 433-456
- Psychophysical examination in patients with post-mastectomy pain.Pain. 2000; 87: 275-284
- Physical and psychological morbidity after axillary lymph node dissection for breast cancer.J Clin Oncol. 1999; 17: 143-149
- Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: A comparative evaluation.Breast Cancer Res Treat. 2002; 73: 31-36
- Lymphedema therapy reduces the volume of edema and pain in patients with breast cancer.Ann Surg Oncol. 2007; 14: 1904-1908
- Ethnic differences in pain coping: Factor structure of the coping strategies questionnaire and coping strategies questionnaire-revised.J Pain. 2004; 5: 304-316
- Fear of pain, pain catastrophizing, and acute pain perception: Relative prediction and timing of assessment.J Pain. 2008; 9: 806-812
- The associations between severity of early postoperative pain, chronic postsurgical pain and plasma concentration of stable nitric oxide products after breast surgery.Anesth Analg. 2006; 103: 995-1000
- Predictors of postoperative pain and analgesic consumption: A qualitative systematic review.Anesthesiology. 2009; 111: 657-677
- Results of a questionnaire survey for symptom of late complications caused by radiotherapy in breast conserving therapy.Breast Cancer. 2006; 13: 197-201
- Treatment of morbidity associated with the management of the axilla in breast-conserving therapy.Acta Oncol. 2000; 39: 349-354
- Pain perception and detailed visual pain mapping in breast cancer survivors.Breast Cancer Res Treat. 2010; 119: 105-110
- Neuropathic pain following breast cancer surgery: Proposed classification and research update.Pain. 2003; 104: 1-13
- Neuropathic pain associated with non-surgical treatment of breast cancer.Pain. 2005; 118: 10-14
- Preincisional paravertebral block reduces the prevalence of chronic pain after breast surgery.Anesth Analg. 2006; 103: 703-708
- Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer.Pain. 1996; 64: 293-302
- Impairments, activity limitations and participation restrictions 6 and 12 months after breast cancer operation.J Rehabil Med. 2005; 37: 180-188
- Persistent postsurgical pain: Risk factors and prevention.Lancet. 2006; 367: 1618-1625
- Persistent postsurgical pain: The path forward through better design of clinical studies.Anesthesiology. 2010; 112: 514-515
- Mastalgia and breast cancer: A protective association?.Cancer Detect Prev. 2002; 26: 192-196
- Predictors and consequences of multiple persistent postmastectomy pains.J Pain Symptom Manage. 2007; 34: 619-627
- Long-term morbidity following axillary dissection in breast cancer patients–clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors.Breast Cancer Res Treat. 2000; 64: 275-286
- Progress in genetic studies of pain and analgesia.Annu Rev Pharmacol Toxicol. 2009; 49: 97-121
- Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion axillary lymph node dissection after breast cancer surgery: A prospective Swiss multicenter study on 659 patients.Ann Surg. 2007; 245: 452-461
- Long-term outcomes of breast cancer patients after endoscopic axillary lymph node dissection: A prospective analysis of 52 patients.Breast Cancer Res Treat. 2005; 90: 85-91
- The consequences of long-time arm morbidity in node-negative breast cancer patients with sentinel node biopsy or axillary clearance.J Surg Oncol. 2005; 92: 23-31
- The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration.BMJ. 2009; 339: b2700
- The gross anatomy of the extrathoracic course of the intercostobrachial nerve.Clin Anat. 2006; 19: 106-111
- Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome.Br J Cancer. 2005; 92: 225-230
- The molecular epidemiology of pain: A new discipline for drug discovery.Nat Rev Drug Discov. 2008; 7: 647-658
- Morbidity related to intercostobrachial nerve damage following axillary surgery for breast cancer.Breast. 1998; 7: 209-212
- Chronic pain following total hip arthroplasty: A nationwide questionnaire study.Acta Anaesthesiol Scand. 2006; 50: 495-500
- Chronic pain following Caesarean section.Acta Anaesthesiol Scand. 2004; 48: 111-116
- Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2.Genome Res. 2010;
- Pain and sensory dysfunction after breast cancer surgery: Neurometer CPT evaluation.Anticancer Res. 2006; 26: 3839-3844
- Localization of the sentinel node of the upper outer breast quadrant in the axillary quadrants.Ann Surg Oncol. 2007; 14: 633-637
- Comparison of quality of life and arm complaints after axillary lymph node dissection vs sentinel lymph node biopsy in breast cancer patients.Br J Cancer. 2003; 89: 648-652
- Chronic pain and other sequelae in long-term breast cancer survivors: Nationwide survey in Denmark.Eur J Pain. 2009; 13: 478-485
- Risk factors for chronic pain following breast cancer surgery: A prospective study.J Pain. 2006; 7: 626-634
- Ethnic identity predicts experimental pain sensitivity in African Americans and Hispanics.Pain. 2007; 129: 177-184
- Chemotherapy-induced peripheral neuropathy as a predictor of neuropathic pain in breast cancer patients previously treated with paclitaxel.J Pain. 2009; 10: 1146-1150
- Treatment-related upper limb morbidity 1 year after sentinel lymph node biopsy or axillary lymph node dissection for stage I or II breast cancer.Ann Surg Oncol. 2004; 11: 1018-1024
- Long term treatment related upper limb morbidity and quality of life after sentinel lymph node biopsy for stage I or II breast cancer.Eur J Surg Oncol. 2006; 32: 148-152
Saarto T, Wiffen PJ: Antidepressants for neuropathic pain. Cochrane Database Syst.Rev. CD005454–2007
- Preservation versus section of intercostal-brachial nerve (IBN) in axillary dissection for breast cancer–a prospective randomized trial.Eur J Surg Oncol. 1998; 24: 158-161
- Comparison of morbidity between axillary lymph node dissection and sentinel node biopsy.Eur J Surg Oncol. 2003; 29: 341-350
- Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.Cancer. 2000; 88: 608-614
- Long-term morbidity of patients with early breast cancer after sentinel lymph node biopsy compared to axillary lymph node dissection.J Surg Oncol. 2006; 93: 109-119
- A retrospective cohort study of post mastectomy pain syndrome.Pain. 1999; 83: 91-95
- Effect of axillary lymph node dissection on prevalence and intensity of chronic and phantom pain after breast cancer surgery.J Pain. 2008; 9: 813-822
- Prevalence, characteristics, and impact of postmastectomy pain syndrome: An investigation of women’s experiences.Pain. 1995; 61: 61-68
- Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer.Ann Surg Oncol. 2002; 9: 745-753
- Chronic post-treatment symptoms in patients with breast cancer operated in different surgical units.Eur J Surg Oncol. 1999; 25: 38-43
- Effect of present pain and mood on the memory of past postoperative pain in women treated surgically for breast cancer.Pain. 1996; 68: 343-347
- Venlafaxine in neuropathic pain following treatment of breast cancer.Eur J Pain. 2002; 6: 17-24
- Treatment-related factors predisposing to chronic pain in patients with breast cancer–a multivariate approach.Acta Oncol. 1997; 36: 625-630
- Pain and other symptoms after different treatment modalities of breast cancer.Ann Oncol. 1995; 6: 453-459
- Pain and other symptoms during the first year after radical and conservative surgery for breast cancer.Br J Cancer. 1996; 74: 2024-2031
- Morbidity associated with axillary surgery for breast cancer.ANZ J Surg. 2004; 74: 314-317
- Impact of the preservation of the intercostobrachial nerve in axillary lymphadenectomy due to breast cancer.Breast J. 2003; 9: 389-392
- Neuropathic pain: Redefinition and a grading system for clinical and research purposes.Neurology. 2008; 70: 1630-1635
- The risk of developing arm lymphedema among breast cancer survivors: A meta-analysis of treatment factors.Ann Surg Oncol. 2009; 16: 1959-1972
- A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer.N Engl J Med. 2003; 349: 546-553
- Risk, severity and predictors of physical and psychological morbidity after axillary lymph node dissection for breast cancer.Eur J Cancer. 2001; 37: 991-999
- Effect of levetiracetam on the postmastectomy pain syndrome.Eur J Neurol. 2008; 15: 851-857
- The postmastectomy pain syndrome: An epidemiological study on the prevalence of chronic pain after surgery for breast cancer.Br J Cancer. 2008; 99: 604-610
- Sensory function and pain in a population of patients treated for breast cancer.Acta Anaesthesiol Scand. 2009; 53: 800-806
- Role of skin biopsy in the diagnosis of peripheral neuropathic pain.Curr Pain Headache Rep. 2009; 13: 191-196
- Prediction of postoperative pain: A systematic review of predictive experimental pain studies.Anesthesiology. 2010; 112: 1494-1502
- Chronic post-thoracotomy pain: A critical review of pathogenic mechanisms and strategies for prevention.Eur J Cardiothorac Surg. 2009; 36: 170-180
- Chemotherapy-induced neuropathy.J Peripher Nerv Syst. 2008; 13: 27-46
Article info
Publication history
Published online: March 25, 2011
Footnotes
This study is a part of the Europain project, funded by the Innovative Medicines Initiative Joint Undertaking (IMI JU)’ Grant No. 115007 (www.imi.europa.eu), and was supported by a grant from the Lundbeck Foundation.
The authors declare no potential conflict of interest.
Identification
Copyright
© 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
