Post-Mastectomy Pain Syndrome (PMPS)

Disease/ Disorder

Definition

Postmastectomy pain syndrome (PMPS) is a clinical diagnosis referring to chronic pain after mastectomy surgery at or near the operative site persisting 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, lateral chest wall, axilla, and upper arm.¹ However, chronic post-breast surgery pain is not limited to mastectomy, it can be a complication of other breast procedures, including lumpectomies, reconstruction after mastectomy, cosmetic breast surgery or breast reduction/augmentation. Therefore, recently the more encompassing name/concept Post Breast Surgery Pain Syndrome (PBSPS) has surfaced, which covers moderate chronic chest wall/breast pain after any breast surgery.² For simplicity, we will continue to use PMPS throughout this review.

Etiology

It is important to note that PMPS can occur with any surgery to the breast including radical or modified mastectomy and reconstruction, hence the term PBSPS. However, rates seem to be highest after complex operations compared with more minimally invasive procedures (e.g., sentinel lymph node dissection).^3,4  In addition to surgical intervention, radiation therapy, chemotherapy, and hormonal therapies, can also contribute directly to the development of pain or the emotional and psychological burden of disease.⁶

While the onset of symptoms can occur several months after surgery, they can persist well beyond the expected timeframe for surgical healing up to many years.⁵ One study found that 52% of breast cancer patients that developed Post Mastectomy pain after surgery, still had the symptoms 7-12 years after.³⁸ Epidemiology including risk factors and primary prevention.

• The estimated prevalence of PMPS is 25% to 60%^6.
  • This wide variability in prevalence is due to the varying definition of PMPS.
• Risk factors
  • Psychosocial^7,8,9,10
    • Anxiety
    • Catastrophizing and frequent somatization
    • Depression
    • Sleep disorders
    • Pre-existing generalized pain conditions
    • Pre-existing surgical area pain
  • Genetic¹⁰
    • Genetic polymorphisms associated with variations in opioid, catecholamine, and chemokine receptors.
  • Surgical
    • Sentinel lymph node biopsy is associated with a lower incidence of PMPS compared to axillary lymph node dissection.¹¹
    • Wide excisions can result in an increased risk of axillary web syndrome, adhesive capsulitis, brachial plexopathy, and rotator cuff injury.¹²
    • Direct injury to nerves during surgery can cause intercostobrachial neuralgia or formation of neuromas.¹³
      • 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 pain¹⁴
    • Postoperative complications¹⁷
      • Infection
      • Hematoma
    • Other^17,18
      • Age <50 years
      • Obesity
      • Diabetes mellitus¹⁹
  • Adjuvant therapy¹⁹
    • Radiation therapy
      • Concomitant complicating factors include increased incidence of tissue fibrosis, neural entrapment, and shoulder dysfunction.^13,14
    • Chemotherapeutic agents
      • Taxanes, Changchun flower alkaloids, platinum drugs
    • Endocrine and HER2-targeted therapy
      • Tamoxifen, aromatase inhibitors
      • Anti-HER2 monoclonal antibodies

Patho-anatomy/physiology

There are numerous potential causes of PMPS. Although the exact mechanisms are yet to be fully understood, it is believed that the pathophysiology of PMPS is likely caused by multiple factors.²⁰ Contributing factors can include injury to nerves, neuromas, fibrosis, and incisional pain. The main nerves at risk of injury during breast cancer procedures are the intercostobrachial, lateral cutaneous branches of the intercostals, medial and lateral pectoral, long thoracic, and thoracodorsal nerves. Currently, PMPS is most commonly attributed to neuralgia of the lateral cutaneous branches of the intercostal nerve. The lateral cutaneous branch traverses the muscles of the lateral chest wall providing sensory information from the skin. Another common involved nerve is the intercostobrachial nerve (ICBN), a cutaneous branch of the second intercostal nerve. The ICBN penetrates through the serratus anterior muscle before traversing the axilla to reach the medial aspect of the arm, where it then merges with the medial brachial cutaneous nerve. The ICBN and lateral cutaneous branches are often encountered within the surgical field during breast surgery and axillary lymph node dissections and are at risk of being severed during the procedure. Furthermore, even if the nerves remain intact, it may still be subject to post-surgical inflammation or traction.²¹

• Direct nerve injury is typically an intraoperative complication associated with transection (neurotmesis).
• Indirect nerve injury can occur both intraoperative or postoperative and is associated with compression, ischemia, stretching and/or retraction of the nerve. For example, poor arm positioning during surgery can cause indirect stretching and retraction injury to the nerves, while post-op formation of hematoma, seroma, lymphedema, or scarring can indirectly cause damage via stretch and compression.²²
• Mechanical stress to peripheral nerves can result in pain due to peripheral and central sensitization.
• Post-surgical adhesions and hematomas²³may also contribute to PMPS by mechanical irritation of local muscle, fascia, and neural structures, causing somatic and visceral pain.
• Postoperative radiotherapy²⁴ 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 clinical diagnosis.

Specific secondary or associated conditions and complications

• Loss of shoulder function
• Muscle weakness of the affected extremity
• Rotator cuff dysfunction
• Adhesive capsulitis
• Brachial plexopathy
• Axillary web syndrome
• Lymphedema
• Neuroma
• Phantom breast pain
• Complex regional pain syndrome
• Psychological and socioeconomic dysfunction
• Fatigue
• Sexual dysfunction

Essentials of Assessment

History

• Lancinating or burning pain at or near the surgical site or in the ipsilateral arm.
  • The majority of patients report pain at multiple sites, studies vary but the breast, lateral chest wall and axilla are typically the most common, followed by the arm.^{25, 26.} 
• Paresthesias, numbness, or hyperesthesia
• Pain aggravated by shoulder movement and stretching.
• Functional loss and sleep disruption
• History of previous shoulder injuries or surgical intervention
• Psychosocial history
• Attenuating factors
  • Rest and massage
• Type of breast cancer and stage of the disease
• Surgical approach and intraoperative course
  • Reconstruction or plans for other surgical interventions.
  • Methods for chemotherapy, radiation treatment, hormonal treatments, immunotherapy
• History of adjuvant therapy
  • Radiation therapy
  • Chemotherapy
  • Endocrine therapy

Physical examination

• Respiratory/Lung Examination:
  • Symmetric chest wall rises decreased breath sounds.
• Skin inspection
  • Neuroma, scar, and vesicular lesions to rule out infectious etiology.
• Breast examination
  • Soft tissue masses, seroma, hematoma, hypertonic pectoralis muscle
• Lymphatic exam
  • New swelling of the upper extremity, upper back, chest
• Shoulder Examination
  • Range of motion and strength assessment to rule out shoulder joint pathology or rotator cuff dysfunction.
• Neurologic Evaluation
  • Intercostobrachial nerve(axillary paresthesia)
  • Thoracodorsal nerve (latissimus weakness)
  • Long thoracic nerve (serratus anterior weakness)
  • Medial/lateral pectoral nerve (pectoralis weakness)

Functional assessment

• Mitigating physical quality of life (QOL) factors
  • Pain
  • Physical appearance
  • Lymphedema
  • Shoulder mobility
• Mitigating psychosocial QOL factors
  • Pain
  • Perceived stress
  • Depression
  • Emotional stability
• 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

Not all patients require imaging. The need for imaging modalities will depend on the patient history and physical examination. The primary concern and goal is to rule out that the pain is from metastatic disease. Imaging can assist in finding lesions if the history and physical exam is consistent with metastasis. After ruling out metastasis imaging can be done to confirm other musculoskeletal/neuromuscular reasons for pain.

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

Supplemental assessment tools

Consider the following

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

Rehabilitation Management and Treatments

A comprehensive multidisciplinary pain management program,²⁹  including medical, psychologic, and interventional therapies complemented by alternative therapies should be considered in the treatment of PMPS.  We have developed a 4 Tiers concept as a guideline to help providers organize the different treatment modalities.  An important concept is that the treating physician should always consider the possibility of cancer recurrence when new or worsening pain is reported.

Conservative treatment and Rehabilitation (Tier 1)

• Physical/Occupational therapy
  Individualizing rehabilitation protocols for PMPS is crucial due to the variability in patients’ symptoms. Tailored physical therapy regimens and exercise can address the specific needs of each patient and has been proven effective in improving patient outcomes.³⁰  Physical therapy after the surgical intervention has shown to improve upper extremity function and quality of life 3 to 6 months after completing treatment as opposed to those only given information about exercise.²⁸ Typically, postmastectomy rehabilitation can commence within the initial week following surgery, provided that the patient has received clearance from the surgical team and the drains have been removed.³¹
  • Desensitization techniques: desensitize affected areas by gradual exposure to more intense sensations over time improving blood flow to reduce pain and inflammation.
    • Tactile stimulation
  • Manual therapy
    • Soft tissue mobilization to address tight muscle groups
    • Myofascial release
    • Trigger point therapy / Dry Needling
  • Therapeutic exercise³¹
    • Improve range of motion (ROM) – progressive passive to active ROM
    • Increase flexibility and reduce stiffness
    • Strengthening of cervical, scapular and shoulder girdle muscles
• Aquatic Therapy
  • Water Exercises are another therapeutic option that can offer advantages by enabling individuals to engage in physical activities that they may not be capable of performing on land.This type of therapeutic exercises in addition to myofascial treatment for PMPS can improve postoperative ROM deficits caused by pain or postsurgical changes of local soft tissue structures.²⁷

Oral and topical medications (Tier 2)

Pharmacologic therapy is typically the initial treatment for PMPS. Anticonvulsant and antidepressant medications have proven efficacy for neuropathic pain and may be the preferred approach in patients with this clinical presentation. However, there are some patients that are hesitant and tired of taking any additional medications and prefer to avoid this therapeutic option and consider interventions as the next step in treatment.

• Oral
  • Gabapentinoids (Gabapentin, Pregabalin)
  • SNRI’s (Venlafaxine, Duloxetine)
  • TCA’s (Amitriptyline)
• Topical
  • Lidocaine
  • Capsaicin

Interventional techniques (Tier 3)

• Ultrasound Guided Procedures
  • Nerve blocks
    • Intercostobrachial nerve block
    • Intercostal nerve block
    • Paravertebral nerve block
    • Fascial plane blocks (inter pectoral plane blocks, serratus anterior plane blocks, transversus thoracic muscle plane block)
  • Botulinum toxin injections
  • Trigger point injections of painful muscles
• Pulsed Radio Frequency (PRF) ablation of thoracic dorsal root ganglia (DRG)
• Neuromodulation
  • Spinal cord stimulation
  • Peripheral nerve stimulation
• Surgery
  • Neuroma resection
  • Axillary scar release
  • Autologous fat grafting
• Alternative  and complementary approaches
  • Acupuncture
  • Hypnosis³²
  • Music therapy

Comprehensive Chronic Pain Rehabilitation Program (Tier 4)

Given the well-established psychological and social components of the pain experience, it is crucial to adopt comprehensive treatment strategies that incorporate interventions targeting physical, behavioral, and psychosocial factors. An integrative rehabilitation approach for managing chronic post mastectomy pain should encompass a team of healthcare professionals trained in different areas, such as pain medicine, physical therapy/rehabilitation, psychology, and sleep medicine. Together, these experts can work collaboratively to design and implement holistic rehabilitation plans that address the unique needs of the patient.

Coordination of care

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.^{34, 35}

Emerging/unique interventions

• Pain assessment⁵
  • Breast Cancer Pain Questionnaire
  • Brief Pain Inventory
  • Short form of the McGill Pain Questionnaire
  • Pain Burden Index
  • Leeds Assessment of Neuropathic Symptoms and Signs
  • 10-item Neuroticism scale
• Psychosocial assessment⁵
  • Pain Catastrophizing Scale
  • Depressive symptoms, anxiety, and sleep disturbance assessment
    • PROMIS
  • Brief Symptom Inventory-18 somatization scale
  • Perceived Stress Scale
  • 10-item Neuroticism scale
• Physical assessment
  • Shoulder
    • 25° or more difference in range of motion between affected and unaffected side
  • Lymphedema assessment
    • Defined as 10% or more volume difference between sides and water submersion test.
  • Impact of Cancer Scale SF-36
• 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

• The etiology of PMPS is not clearly defined, though it may be incited by perioperative trauma and persists because of maladaptive psychopathology.
• 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.
• Presurgical patient education and perioperative pain/surgical management may discourage PMPS evolution; postoperative rehabilitation may reduce symptoms.
• Cognitive-behavioral therapy after onset can offer improved global function.
• Treatment may be challenging and requires a multimodal approach for adequate care. Practitioners should always consider the possibility of cancer recurrence when treating PMPS.

Cutting Edge/ Emerging and Unique Concepts and Practice

• Intraoperative
  • Autologous fat grafting³⁶ 
    • Aesthetic and adhesion management
  • Axillary web syndrome management using therapeutic ultrasound and/or myofascial release³⁷
  • Maximize analgesia
• Acute pain management
  • Lidocaine infusion
  • Ketamine infusion
  • Intravenous ibuprofen
  • Intravenous acetaminophen
• Postoperative subacute and chronic pain management
  • Spinal cord stimulation
  • Peripheral field stimulation
  • Ablation of intercostal or intercostobrachial nerve
  • Botulinum toxin
  • Acupuncture and massage
• Imaging
  • Targeting the pain modulatory systems and functional magnetic neuroimaging

Gaps in the Evidence-Based Knowledge

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

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Original Version of the Topic

Sayed E. Wahezi, MD, Paras Shah, MD. Post-Mastectomy Pain Syndrome (PMPS). 9/20/2014

Previous Revision(s) of the Topic

Jesuel Padro-Guzman, MD, Hanna Oh, MD, Franchesca König, MD. Post-Mastectomy Pain Syndrome (PMPS). 11/19/2019

Author Disclosure

Raul A. Rosario-Concepcion, MD
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Daniel Almodovar-Frau, MD
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Julia Carter, MD
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