Author(s): Jesuel Padro-Guzman, MD, Hanna Oh, MD, Franchesca König, MD
Originally published: September 20, 2014 Last updated: November 19, 2019
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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 three months after surgery. It is a distinct entity and should not be confused with complex regional pain syndrome or phantom breast pain. Symptoms can affect the anterior thorax, axilla, and upper arm.1

Etiology

It is important to note that PMPS can occur with any surgery to the breast including radical or modified mastectomy and reconstruction. However, rates seem to be highest after complex operations compared with more minimally invasive procedures (e.g., sentinel lymph node dissection)2,3

While the onset of symptoms can occur several months after surgery, they can persist well beyond the expected timeframe for surgical healing and up to many years.4 In addition to surgical intervention, treatment of breast cancer, including radiation therapy, chemotherapy, and hormonal therapies, can also contribute directly to the development of pain or the emotional and psychological burden of disease.5

Epidemiology including risk factors and primary prevention

  1. The estimated prevalence of PMPS is 25% to 60%5
    • This wide variability in prevalence is due to the varying definition of PMPS
  2. Risk factors
    • Psychologic6,7,8
      • Anxiety
      • Catastrophizing
      • Depression
      • Pre-existing generalized pain condition
    • Surgical
      • Sentinel lymph node biopsy is associated with a lower incidence of PMPS compared to axillary lymph node dissection9
      • Wide excisions can result in an increased risk of axillary web syndrome, adhesive capsulitis, brachial plexopathy, and rotator cuff injury10
      • Direct injury to nerves during surgery can cause intercostobrachial neuralgia or formation of neuromas11
        • Subsequent sensory disturbances, such as phantom breast pain, allodynia, numbness, and paresthesias, can also occur.
      • Other variables, such as surgical approach and breast conservative or reconstructive strategies have not been linked to long-term pain outcomes.
    • Post-Operative
      • Poorly controlled immediate postoperative pain12
      • Radiation therapy
        • Concomitant complicating factors include increased incidence of tissue fibrosis, neural entrapment, and shoulder dysfunction.13,14
      • Postoperative complications15
        • Infection
        • Hematoma
      • Other15,16
        • Age <50 years
        • Obesity

Patho-anatomy/physiology

There are numerous potential causes of PMPS. Contributing factors can include injury to nerves, neuromas, fibrosis, and incisional pain.

  1.  Mechanical stress to peripheral nerves can result in pain due to peripheral and central sensitization.
  2. Postsurgical adhesions and hematomas17 may also contribute to PMPS by mechanical irritation of local muscle, fascia, and neural structures, causing somatic and visceral pain.
  3. Postoperative radiotherapy18 may lead to the development of PMPS by inducing local neuritis, myonecrosis or 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
  7. Lymphedema
  8. Neuroma
  9. Phantom breast pain
  10. Complex regional pain syndrome
  11. Psychologic and socioeconomic dysfunction
  12. Fatigue
  13. Sexual dysfunction

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. History of previous shoulder injuries or surgical intervention
  6. Psychosocial
    • Mood changes
    • Difficulty at work
    • Reduction of physical activities
  7. Attenuating factors
    • Rest and massage
  8.  Type of breast cancer and stage of the disease
  9.  Surgical approach and intraoperative course
    •  Reconstruction or plans for other surgical interventions
    • Methods for chemotherapy, radiation treatment, hormonal treatments, immunotherapy

Physical examination

  1. Respiratory/Lung Examination:
    • Symmetric chest wall rises decreased breath sounds
  2. Skin inspection
    • Neuroma, scar, and vesicular lesions to rule out infectious etiology
  3. Breast examination
    • Soft tissue masses, seroma, hematoma, hypertonic pectoralis muscle
  4. Lymphatic exam
    • New swelling of the upper extremity, upper back, chest
  5. Shoulder Examination
    • Range of motion and strength assessment to rule out shoulder joint pathology or rotator cuff dysfunction
    • Neuromuscular Assessment
    • Intercostobrachial (axillary paresthesia)
    • Thoracodorsal (latissimus weakness)
    • Long thoracic (serratus anterior weakness)
    • Medial/lateral pectoral (pectoralis weakness)
    • Neurologic examination to evaluate for cervical radiculopathy
    • Sensory-motor testing, reflexes, Spurling maneuver.

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

Imaging modalities to consider

  1. Radiographs
    • Shoulder
      • Glenohumeral or acromioclavicular arthritis
    • Chest
      • Intraparenchymal lung disease
      • Rib fractures
  2. Musculoskeletal ultrasound
    • Shoulder
      • Tendinopathy, bursitis, rotator cuff tears
  3. Computed tomography (CT) scan
    • Chest
      • Metastatic lesions in the lung or ribs
  4. Magnetic resonance imaging (MRI) of the cervical spine
    • Bony metastases
    • Radiculopathy
  5. MRI shoulder
    • Rotator cuff tendinopathy, tears, bursitis, adhesive capsulitis, labral tear, and skeletal metastases to the humerus
  6. MRI brachial plexus
    • Brachial plexus injury

Supplemental assessment tools

Consider 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
    • Axillary nerve block

3. REHABILITATION MANAGEMENT AND TREATMENTS

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

  1. Exercise has demonstrated improved patient outcomes.19
    • Tailored physical therapy regimens20 for PMPS can improve postoperative range of motion deficits caused by pain or postsurgical changes of local soft tissue structures.
    • Patients who underwent physical therapy after the surgical intervention had improved upper extremity function and quality of life 3-6 month after completing treatment as opposed to those only given information about exercise.21

Therapeutic interventions should focus on early desensitization techniques, myofascial mobilization, pectoralis and latissimus dorsi stretching, cervical/shoulder/scapular range of motion and shoulder girdle strengthening.

  1. A comprehensive multidisciplinary pain management program,22 including medical, psychologic, and interventional therapies complemented by alternative therapies should be considered in the treatment of PMPS.
  2. The treating physician should always consider the possibility of cancer recurrence when new or worsening pain is reported.

At different disease stages

Consider the following:

  1. Preoperative
    • Patient education about PMPS
  2. Perioperative pain control
    • Minimization of surgical dissection area
    • Nerve-sparing procedures
    • Adequate intraoperative analgesia
      • Intravenous analgesia
      • Paravertebral block
  3. Postoperative (up to 1 month after surgery)
    • Intravenous analgesia (inpatient only)
      • Ibuprofen
      • Acetaminophen
      • Opiates
      • Ketamine
    • Oral analgesia
      • Nonsteroidal anti-inflammatories
      • Acetaminophen
      • Opiates
      • Antiseizure medications
      • Nonselective serotonin reuptake inhibitors
      • Antispasmodics
    •  Topical
      • Lidocaine
      • Prilocaine/lidocaine
      • Capsaicin23
    •  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)
    • Consider tapering any above mentioned oral or topical pain medications
    • Evaluate for the need for 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
    • Those mentioned above under the Subacute section with the addition of the following:
      • Cognitive-behavioral therapy
      • Scar management
      • Spinal cord stimulation
      • Peripheral nerve stimulation
      • Peripheral field stimulation

Coordination of care

  1. Co-management with pain service for management of acute and chronic 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.24,25

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 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 may be challenging and requires a multimodal approach for adequate 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 grafting26
      • Aesthetic and adhesion management
    • Axillary web syndrome management using therapeutic ultrasound and/or myofascial release27
    • 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

REFERENCES

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  3. Smith WC, Bourne D, Squair J, et al. A retrospective cohort study of post mastectomy pain syndrome. Pain. 1999; 83:91-95.
  4. Vilholm OJ, Cold S. Rasmussen L, et al. The postmastectomy pain syndrome: an epidemiological study on the prevalence of chronic pain after surgery for breast cancer. Br J Cancer. 2008; 99:604-10.
  5. Gartner R, Jensen MB, Nielsen J, et al. Prevalence of and factors associated with persistent pain following breast cancer surgery. Jama. 2009; 302:1985-1992.
  6. 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.
  7. Miaskowski C, Cooper B, Paul SM et all. Identification of patient subgroups and risk factors for persistent breast pain following breast cancer surgery. J Pain. 2012; 13:1172-1187.
  8. Schrieber KL, Martel MO, Shnol H et al. Persistent pain in post mastectomy patients: comparison of psychological, medical, surgical and psychosocial characteristics between patients with and without pain. Pain. 2013; 154:660-668.
  9. Mansel RE, Fallowfield L, Kissin M. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC trial. J Natl Cancer Inst. 2006; 98:599-609.
  10. Hayes SC, Johannson K, Stout NL, et al: Upper body morbidity after breast cancer: incidence and evidence for evaluation, prevention, and management within a prospective surveillance model of care. Cancer. 2012; 118:2237-2249.
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  20. 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.
  21. Beurskens CH, van Uden CJ, Strobbe LJ. The efficacy of physiotherapy upon shoulder function following axillary dissection in breast cancer, a randomized controlled study. BMC Cancer. 2007; 7:166.
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Original Version of the Topic

Sayed E. Wahezi, MD, Paras Shah, MD. Post-Mastectomy Pain Syndrome (PMPS). 09/20/2014.

Author Disclosure

Jesuel Padro-Guzman, MD
Nothing to Disclose

Hanna Oh, MD
Nothing to Disclose

Franchesca König, MD
Nothing to Disclose