Post-Mastectomy Pain Syndrome (PMPS)

Author(s): Sayed E. Wahezi, MD, Paras Shah, MD

Originally published:09/20/2014

Last updated:09/20/2014

1. DISEASE/DISORDER:

Definition

Postmastectomy pain syndrome (PMPS) is a diagnosis of exclusion referring to chronic pain that develops after breast cancer surgery at or near the operative site and persists beyond 3 months after surgery. It is a distinct entity and should not be confused with complex regional pain syndrome or phantom breast pain.

Etiology

PMPS can occur with any surgery to the breast, including mastectomy, lumpectomy, reconstruction, and augmentation; however, rates seem to be highest after invasive surgeries compared with more minimally invasive procedures (eg, sentinel lymph node dissection).1,2

Epidemiology including risk factors and primary prevention

  1. The estimated prevalence of PMPS is 25% to 60%1
  2. Postoperative shoulder and/or thoracic pain incidence as a consequence of breast surgery for cancer is 27%1,2
    • Incidence of pain 6 months postsurgery is 52.9%1,2
    • Of those, 52.6% demonstrate involvement of the intercostobrachial nerve1,2
      • 1.3% of patients develop neuromas3
      • 3.2% develop phantom breast pain3
  3. Risk factors
    • Psychologic4
      • Anxiety
      • Depression
      • Catastrophizing
    • Surgical
      • Surgical technique
      • Incision site and type
      • Wide resection
      • Poorly controlled immediate postoperative pain
      • Postoperative complications
        • Infection
        • Hematoma
    • Other
      • Age <50 years
      • Chemotherapy
      • Radiation
      • Obesity
      • Generalized pain

Patho-anatomy/physiology

  1. Most investigators believe PMPS is caused by pathologic postsurgical changes of the intercostobrachial nerve.5,6The intercostobrachial nerve is frequently stretched or ligated during breast surgery resections. This mechanical stress can result in pain hypersensitivity by neurophysiologic changes that lead to peripheral and central sensitization.
  2. Postsurgical adhesions and hematoma7may also contribute to PMPS by mechanical irritation of local muscle, fascia, and neural structures causing somatic and visceral pain.
  3. Postoperative radiotherapy8may also lead to the development of PMPS by inducing local subclinical necrosis, neuritis, and myositis/fibrosis.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Onset of PMPS may begin immediately after surgery; however, diagnosis of PMPS is not made until 3 to 6 months after surgery to allow for the natural course of surgical healing. Pain may also begin insidiously after surgery and worsen in an ill-defined time frame. Other than surgical changes, the patient lacks visible or palpable surface transformations at the painful site on initial diagnosis. There are no accepted laboratory or radiographic criteria used to diagnose PMPS; it is a diagnosis of exclusion. The lack of reliable clinical markers mitigate this syndrome’s disease trajectory into temporal classifications (eg, phases or stages).

Specific secondary or associated conditions and complications

  1. Loss of shoulder function
  2. Muscle weakness of the affected extremity
  3. Rotator cuff dysfunction
  4. Adhesive capsulitis
  5. Brachial plexopathy
  6. Axillary web syndrome (cord shaped scarring of subcutaneous axillary tissue)
  7. Lymphedema
  8. Neuroma
  9. Phantom breast pain
  10. Complex regional pain syndrome
  11. Psychologic and socioeconomic dysfunction
    • Depression
    • Loss of employment

2. ESSENTIALS OF ASSESSMENT

History

  1. Lancinating or burning pain at or near the surgical site
  2. Pain aggravated by shoulder movement and stretching
  3. Hypersensitivity around the surgical site
  4. Functional loss and sleep disruption
  5. Psychosocial
    • Mood changes
    • Difficulty at work
    • Reduction of physical activities
  6. Attenuating factors
    • Rest and massage
  7. Medications
    • Amitriptyline
    • Venlafaxine
    • Capsaicin

Physical examination

• General inspectionfor muscle wasting, asymmetry, and gross masses
• Lung examforchest wall adhesion, lung masses, infection, and symmetric chest wall rise
• Skin exam forneuroma, scar, and vesicular lesions to rule out infectious etiology
• Lymphatic examination
• Shoulder mobility assessment to rule out shoulder joint pathology as a cause for pain
• Neuromuscular assessment

  1. Intercostobrachial(axillary paresthesia)
  2. Thoracodorsal(latissimus weakness)
  3. Long thoracic(serratus anteriorweakness)
  4. Medial/lateralpectoral (pecoralis weakness)

•Exam toevaluate forlower cervical radiculopathy

  1. Spurling test
  2. Sensory-motor testing andreflexes

•Sensory assessment dermatomes T1-6 (anterior and posterior chest) andaxilla

Functional assessment

  1. Mitigating physical quality of life (QOL) factors
    • Pain
    • Physical appearance
    • Lymphedema
    • Shoulder mobility
  2. Mitigating psychosocial QOL factors
    • Pain
    • Perceived stress
    • Depression
    • Emotional stability
  3. Outcome surveys
    • Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
      • Impact of Cancer Scale SF-36
    • National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) short-form surveys

Laboratory studies

We suggest the following:

  1. Biopsy of breast tissue
    • Treatment/prognostic markers
      • Estrogen tumor markers
      • Progesterone tumor markers
      • Human epidermal growth-factor receptor 2 (HER2/neu)
    • Cancer aggressiveness
      • Urokinase-type plasminogen activator/plasminogen activator inhibitor-1
  2. Genetic testing
    • Breast cancer genes 1 and 2
  3. Markers for treatment efficacy
    • Cancer antigen 15-3
    • Cancer antigen 27-29
    • Carcinoembryonic antigen

Imaging

We suggest the following:

  1. Radiographs
    • Chest
      • Intraparenchymal lung disease
      • Rib fracture
    • Shoulder
  2. Musculoskeletal ultrasound evaluation of shoulder, chest wall, and axilla
  3. Mammography, magnetic resonance imaging (MRI), or positron emission tomographic scans to assess the following:
    • Malignancy
    • Radiculopathy
    • Shoulder dysfunction
  4. Computed tomography scan
  5. MRI neurography to assess brachial plexus involvement
  6. Lymphography
  7. Lymphangiography
  8. Magnetic resonance lymphography

Supplemental assessment tools

We suggest the following:

  1. Electrodiagnosis to assess for radiculopathy, plexopathy, and neuropathy (paraneoplastic, chemotherapy, radiation)
  2. Diagnostic interventional procedures
    • Intercostobrachial nerve block
    • Intercostal nerve blocks
    • Stellate ganglion nerve block
    • Suprascapular nerve block

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

Though there are no published PMPS guidelines, our recommendations are as follows:

  1. Exercise has demonstrated improved patient outcomes.9
    • Tailored physical therapy regimens10for PMPS can improve postoperative range of motion deficits caused by pain or postsurgical changes of local soft tissue structures.
    • Physical modalities must be implemented cautiously because their safety and efficacy is uncertain.
  2. A comprehensive multidisciplinary pain management program,11including medical, psychologic, and interventional therapies complimented by alternative therapies should be considered in the treatment of PMPS.
  3. The treating physician should always consider the possibility of cancer recurrence when new or worsening pain is reported.

At different disease stages

We suggest the following:

  1. Preoperative
    • Patient education about PMPS
  2. Perioperative pain control
    • Recommend minimization of surgical dissection area
    • Recommend nerve sparing procedures
    • Adequate intraoperative analgesia
      • Intravenous analgesia
      • Paravertebral block
  3. Postoperative (up to 1 month after surgery)
    • Good postoperative pain control
      • Intravenous analgesia (inpatient only)
        • Ibuprofen
        • Acetaminophen
        • Opiates
        • Ketamine
    • Oral analgesia
      • Nonsteroidal anti-inflammatories
      • Acetaminophen
      • Opiates
      • Antiseizure medications
      • Nonselective serotonin reuptake inhibitors
      • Antispasmotics
    • Topical
      • Lidocaine
      • Prilocaine/lidocaine
      • Capsaicin12
    • Continuous
      • Paravertebral block via controlled local anesthesia delivery
    • Rehabilitation
      • Shoulder and soft tissue mobilization
      • Desensitization therapy
      • Transcutaneous electrical nerve stimulation (TENS)
  4. Subacute (up to 3 months after surgery)
    • Oral analgesia
      • As previously listed
    • Topical
      • As previously listed
    • Rehabilitation
      • Shoulder and soft tissue mobilization
      • Desensitization therapy
      • TENS
      • Lymphedema management (if appropriate)
    • Interventional
      • Intercostal nerve block/thoracic dorsal root ganglia radiofrequency ablation
      • Intercostobrachial nerve block
      • Botulinum toxin injections
      • Trigger point injections of painful muscles
      • Paravertebral nerve block
  5. Chronic
    • All aforementioned under the Subacute section with the addition of the following:
      • Cognitive behavioral therapy
      • Scar management
      • Chest wall adhesions
      • Spinal cord stimulation
      • Peripheral nerve stimulation
      • Peripheral field stimulation

Coordination of care

  1. Development of acute pain service for management of postoperative pain.
  2. Providing multimodal analgesia to improve postoperative pain treatment.
  3. Patients should be managed by an extended multidisciplinary team (pain, hematology, surgery, rehabilitation, psychiatry) and enrolled in psychologist-administered cancer survivor support groups.

Patient & family education

Educational pamphlets and social media can educate patients with PMPS about managing the effects of disease and treatment; cancer survivor groups can also be effective in reducing emotional stressors, which can be a precursor to PMPS.13,14

Emerging/unique Interventions

  1. Pain assessment4
    • Breast Cancer Pain Questionnaire
    • Brief Pain Inventory
    • Short form of the McGill Pain Questionnaire
    • Pain Burden Index
    • Leeds Assessment of Neuropathic Symptoms and Signs
  2. Psychosocial assessment4
    • Pain Catastrophizing Scale
    • Depressive symptoms, anxiety, and sleep disturbance assessment
      • PROMIS
    • Brief Symptom Inventory-18 somatization scale
    • Perceived Stress Scale
    • 10-item Neuroticism scale
  3. Physical assessment
    • Shoulder
      • 25° or more difference in range of motion between affected and nonaffected side
    • Lymphedema assessment
      • Defined as 10% or more volume difference between sides and water submersion test
  4. Global assessment
    • SF-36
    • Impact of Cancer Scale SF-36

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  1. The etiology of PMPS is not clearly defined, though it may be incited by perioperative trauma and persists because of maladaptive psychopathology.
  2. Although PMPS can be managed at any point in time, it is best to recognize early signs and symptoms in order to institute treatment as quickly as possible.
  3. Presurgical patient education and perioperative pain/surgical management may discourage PMPS evolution; postoperative rehabilitation may reduce symptoms.
  4. Cognitive behavioral therapy after onset can offer improved global function.
  5. Treatment is challenging and requires a multimodal approach for effective care. Practitioners should always consider the possibility of cancer recurrence when treating PMPS.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

  1. Intraoperative
    • Autologous fat grafting15
      • Aesthetic and adhesion management
    • Axillary web syndrome management using therapeutic ultrasound and/or myofascial release16
    • Maximize analgesia
  2. Acute pain management
    • Lidocaine infusion
    • Ketamine infusion
    • Intravenous ibuprofen
    • Intravenous acetaminophen
  3. Postoperative subacute and chronic pain management
    • Spinal cord stimulation
    • Peripheral field stimulation
    • Ablation of intercostal or intercostobrachial nerve
    • Botulinum toxin
    • Acupuncture and massage
  4. Imaging
    • Targeting the pain modulatory systems and functional magnetic neuroimaging

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

  1. Acupuncture and massage for management is encouraging but inconclusive
  2. Nutritional intervention in chronic postoperative pain
  3. Surgery-induced spinal pain amplification mechanisms
  4. Interventional pain management
    • Sympathetic blocks
    • Intercostal nerve blocks/radiofrequency ablation
    • Radiofrequency ablation/chemoablation of intercostobrachial nerve
    • Spinal cord stimulation
    • Peripheral nerve and field stimulation

REFERENCES

1. Schulze T, Mucke J, Markwardt J, et al. 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.

2. Smith WC, Bourne D, Squair J, et al. A retrospective cohort study of post mastectomy pain syndrome.Pain. 1999;83:91-95.

3. Tasmuth T, von Smitten K, Hietanen P, et al. Pain and other symptoms after different treatment modalities of breast cancer.Ann Oncol. 1995;6:453-459.

4. Belfer I, Schreiber KL, Shaffer JR, et al. Persistent postmastectomy pain in breast cancer survivors: analysis of clinical, demographic, and psychosocial factors.J Pain. 2013;14:1185-1195.

5. Vecht CJ. Arm pain in the patient with breast cancer.J Pain Symptom Manage. 1990;5:109-117.

6. Foley KM. Pain syndromes in patients with cancer.Med Clin North Am.1987;71:169-184.

7. Blunt C, Schmiedel A. Some cases of severe post-mastectomy pain syndrome may be caused by an axillary hematoma. Pain. 2004;108:294-296.

8. Amichetti M, Caffo O. Pain after quadrantectomy and radiotherapy for early-stage breast cancer: incidence, characteristics and influence on quality of life.Oncology. 2003;65:23-28.

9. Hase K, Kamisako M, Fujiwara T, et al. The effect of zaltoprofen on physiotherapy for limited shoulder movement in breast cancer patients: a single-blinded before-after trial.Arch Phys Med Rehabil. 2006;87:1618-1622.

10. de Rezende LF, Franco RL, de Rezende MF, Beletti PO, Morais SS, Gurgel MS. Two exercise schemes in postoperative breast cancer: comparison of effects on shoulder movement and lymphatic disturbance.Tumori. 2006;92:55-61.

11. Robb KA, Williams JE, Duvivier V, et al. A pain management program for chronic cancer treatment-related pain: a preliminary study.J Pain. 2006;7:82-90.

12. Dini D, Bertelli G, Gozza A, Forno GG. Treatment of the post-mastectomy pain syndrome with topical capsaicin.Pain. 1993;54:223-226.

13. Kwekkeboom K. Post mastectomy pain syndromes.Cancer Nurse. 1996;19:37-43.

14. Syrjala KL, Abrams JR, Polissar NL, et al. Patient training in cancer pain management using integrated print and video materials: a multisite randomized controlled trial.Pain. 2008;135:175-186.

15. Caviggioli F, Vinci V, Codolini L. Autologous fat grafting: an innovative solution for the treatment of post-mastectomy pain syndrome.Breast Cancer. 2013;20:281-282.

16. Fourie WJ, Robb KA. Physiotherapy management of axillary web syndrome following breast cancer treatment: discussing the use of soft tissue techniques.Physiotherapy. 2009;95:314-320.

Bibliography

Ebaugh D, Spinelli B, Schmitz KH. Shoulder impairments and their association with symptomatic rotator cuff disease in breast cancer survivors.Med Hypotheses. 2011;77:481-487.

Edwards RR, Mensing G, Cahalan C, et al. Alteration in pain modulation in women with persistent pain after lumpectomy: influence of catastrophizing.J Pain Symptom Manage. 2013;46:30-42.

Nesvold IL, Reinertsen KV, Fosså SD, et al. The relation between arm shoulder problems and quality of life in breast cancer survivors: a cross-sectional and longitudinal study.J Cancer Surviv. 2011;5:62-72.

Author Disclosure

Sayed E. Wahezi, MD
Nothing to Disclose

Paras Shah, MD
Nothing to Disclose

 

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