Post Mastectomy Pain Syndrome

Several studies have shown that persistent pain after treatment for breast cancer is a common problem, ranging between 25% and 60% depending on definition, measurement, and methods of treatment. The term refers to pain in and around the area of surgery lasting beyond three months after surgery when all other causes of pain such as recurrence have been ruled out. Persistent pain after treatment has a considerable negative influence on the quality of life in breast cancer survivors, and persistent pain, in general, has important economic consequences for the healthcare system. Many potential pre-, intra-, and postoperative risk factors for persistent pain after treatment for breast cancer have been proposed, including young age, pain elsewhere in the body, radiotherapy, and the extent of axillary surgery.

The global epidemiology of persistent pain after breast cancer treatment (PPBCT) is still incomplete probably because of the neglected recognition of PPBCT. It is conceivable that the incidence of PPBCT may be underestimated, since there may be multiple barriers for patients to report their pain to their physicians. Ongoing pain after treatment is an unexpected reality for some women with breast cancer and may induce anxiety about cancer recurrence, and some women may not report persistent pain for fearing that they may find out to be cancer recurrence.

Estimates of the prevalence of phantom breast sensation in patients following mastectomy have been as high as 60– 80%. Estimates of the prevalence of ICN (or PMPS) also vary widely. Stevens et al. (1995) reported that the prevalence of PMPS was 20% after breast cancer surgery.

 

Types of breast cancer surgery

Radical mastectomy

This operation was developed by Halsted in the late 19th century. It involves removing the breast, skin and fat, pectoralis major and minor muscles of the chest, and all the lymph nodes under the ipsilateral arm. It is the most disfiguring breast cancer surgery and exploration of other options began in the 1970s when it was realized that most breast cancer recurrences are not in the chest muscles.

Modified radical mastectomy

The pectoralis muscles are not removed but all other aspects of radical mastectomy are retained. Although removal of pectoralis minor was included with the initial modifications, it is now rarely performed.

Lumpectomy with axillary node dissection

The primary tumor and a margin of normal tissue are removed and axillary node dissection is performed through a separate incision in the armpit. Post-operative radiation therapy is administered to the remaining breast and the tumor bed. When disease is found in the axillary nodes, post-operative chemotherapy is administered.

Breast-conserving surgery (lumpectomy)

Breast-conserving surgical treatments have evolved rapidly in recent years and currently account for as much as 40% of breast cancer surgery. Although commonly referred to as lumpectomy, these procedures have also been termed breast preservation, conservative breast surgery, wide local excision, partial mastectomy, segmentectomy, or tylectomy. Lumpectomy involves removal of the primary tumour and a margin of normal tissue, and it is important to distinguish lumpectomy from lumpectomy with axillary node dissection and lumpectomy with sentinel node biopsy. Patients who undergo only lumpectomy generally have earlier breast cancer (in situ disease) than those who require an axillary procedure.

Lumpectomy with sentinel lymph node biopsy

This is the most recent and least invasive option. The sentinel lymph node (i.e. the first axillary lymph node to receive drainage from the breast tumor) is identified by injecting a dye or radiolabelled colloid into the area of the tumor before surgery and then the labeled node is identified and removed for pathologic examination. If no tumor is found within this node, the patient does not undergo axillary dissection. With sentinel node biopsy, only those patients with disease in the sentinel lymph node undergo axillary dissection, sparing many patients from axillary dissection and its complications. Post-operative breast radiation therapy is administered to all patients.

Anatomical considerations

The innervation of the cutaneous and subcutaneous (adipose, lactiferous) structures of the breast is simple, with somatic and preganglionic sympathetic innervation being supplied through the medial and lateral cutaneous branches of the ventral ramus of the third through sixth intercostal nerves. The lateral cutaneous branch of T2 (intercostobrachial nerve) crosses the axilla to innervate the upper medial portion of the arm while the lateral and anterior branches innervate the anterior chest and upper back. T3 innervates the skin of the axilla as well as the anterior and posterior torso, and T4 and below are restricted to the torso. The nipple is primarily innervated by T4 .

Axillary dissection poses risks to the intercostobrachial nerve, from stretch during retraction as well as from frank transection. Many patients will be left with an area of numbness on the upper inner arm, signifying damage to the intercostobrachial nerve, but only a minority of these will be painful. Other nerves at risk for damage from axillary dissection include the medial cutaneous nerve of the arm, which contains fibers from C8 and T1 and arises from the medial cord of the brachial plexus. It can be harmed during section of the tributaries of the axillary vein, leaving patients with a sensory loss on the lower medial skin of the upper arm. Pain accompanied by a sensory loss in one of these areas provides the basis for a diagnosis of injury to these specific nerves.

Neuropathic pain arises from damage to nociceptive axons; damage to primarily motor nerves is less likely to cause chronic pain. However, even motor nerves have sensory nervi nervorum and vasorum . Vulnerable motor nerves in the area include the medial and lateral pectoral nerves, which innervate the pectoralis minor and major muscles and are lost during resection of these muscles. The long thoracic nerve to the serratus anterior muscle runs along the posterior part of the medial wall of the axilla behind the axillary nodes. Damage produces ‘ winging’ of the scapula. The thoracodorsal nerve to the latissimus dorsi muscle runs vertically through the axilla in close proximity to the subscapular artery and vein. Preservation of these neurovascular structures is required if a latissimus dorsi flap is needed for reconstructive breast surgery. Weakness of the latissimus dorsi (which adducts the upper arm) can usually be compensated for by the teres major and pectoralis major muscles.

Classification of chronic pain following breast surgery

Persistent pain in a patient with a prior surgical procedure for breast cancer can occur for many reasons, including tumor recurrence, complications of radiotherapy or chemotherapy, or surgical injury. Chronic pain that is a direct consequence of surgery can be either nociceptive – for example, resulting from injury to ligament or muscle – or neuropathic in origin. Nociceptive pain usually resolves as damaged tissues heal, whereas pain from neuronal dysfunction can persist indefinitely.

Jung et al distinguished four different types of chronic neuropathic pain following breast cancer surgery due to surgical trauma:

Phantom Breast Pain

Phantom Breast Pain is pain experienced in the area of a removed breast. Patients commonly experience the sensation that the removed breast is still present after a radical mastectomy or a modified radical mastectomy. In considering chronic pain following breast cancer surgery, it is important to distinguish non-painful phantom sensation from phantom pain. Non-painful phantom breast sensation is a sensory experience of a removed breast that still feels present. Phantom breast pain is a sensory experience of a removed breast that is still present and is painful. Phantoms, either painful or non-painful, can occur after removal of any innervated body part.

Neuroma pain

Neuromas can form whenever peripheral nerves are severed or injured. Macroneuromas consist of a palpable mass of tangled axons unable to regenerate to their target, fibroblasts, and other cells, whereas microneuromas contain small numbers of axons and may not be palpable. Both mastectomy and lumpectomy leave a scar in which neuromas can form. Axons entrapped within these scars can cause spontaneous pain and severe mechanosensitivity. Neuroma pain may be more common following lumpectomy than mastectomy.

Other nerve injury pain

Other nerve injury pain may result from damage or traction to the medial and lateral pectoral, long thoracic, or thoracodorsal nerves, which are routinely spared but may be injured by scarring or by traction during mastectomy.

Post-mastectomy pain syndrome (PMPS)

Foley and colleagues (Granek et al., 1984; Foley, 1987 ) described a distinct syndrome of pain and sensory abnormalities following mastectomy that they termed post-mastectomy pain syndrome (PMPS). In PMPS, pain is typically localized to the axilla, medial upper arm, and/or the anterior chest wall on the affected side. Damage to the intercostobrachial nerve, which can occur with axillary node dissection, has been considered the most common cause of PMPS. Intercostobrachial Neuralgia is pain often accompanied by sensory changes, in the distribution of the intercostobrachial nerve following breast cancer surgery with or without axillary dissection. The intercostobrachial nerves run from the chest wall through the axilla to innervate the shoulder and upper arm. With axillary node dissection, these nerves are impossible to spare.

Unfortunately, the risk of damage to the intercostobrachial nerve in breast-conserving surgery can be at times equivalent to that which occurs with complete mastectomy. There is a wide variation in the size, location, and branching of the intercostobrachial nerve which may explain the high risk of damage to these nerves irrespective of surgical approach.

Because patients with chronic pain following lumpectomy with axillary node dissection, as well as those with PMPS, can have neuropathic pain, at present intercostobrachial neuralgia (ICN) is a more appropriate term than PMPS for the neuropathic pain syndrome that appears to result from damage to the intercostobrachial nerve.

RISK FACTORS

There are a number of assumed factors causing or perpetuating persistent neuropathic pain after breast cancer surgery. There is, however, a lack of large-scale multiple risk factor studies identifying the variables as independent risk factors or evaluating their relationships with other variables, which are known to affect the development of chronic pain. From the literature currently available, the most well-established risk factors for developing phantom breast pain and other related-neuropathic pain syndromes are severe acute postoperative pain and greater post-operative use of analgesics.These are consistent with all persistent post-surgical neuropathic pain syndromes. Hence, it is assumed that the relief of severe acute pain may reduce the risk of chronic pain. Pre-operative breast pain correlated with increased phantom breast sensation and phantom breast pain.

Evidence to support age as a risk factor is currently inconclusive. Younger patients, however (under 35 years of age) have poorer prognosis due to more aggressive cancers or higher rates of recurrence.

Nerve preservation approaches have shown reduced incidence of sensory deficits (53 percent vs. 84 percent of women) but nerve sparing is only successful in 65 percent of the cases where it was attempted.

Chemotherapy and radiation therapy are reported not to be direct risk factors for phantom breast pain but may cause additional pain through peripheral neuropathy, plexopathy, and plexitis.

Psychosocial distress has been found to be both a consequence of chronic pain and a risk factor for its development. In particular, Katz et al found that greater preoperative anxiety independently predicted both clinically meaningful pain in the immediate postoperative period as well as for a period of up to 30 days post surgery. While younger age and being unmarried were also independently associated with persisting acute pain, these were postulated to reflect the psychosocial effects of reduced social support.

PROGNOSIS

There is some evidence that chronic pain and sensory abnormalities do decrease over time. Unfortunately, there are very few studies looking at the natural history of pain duration of individual neuropathic pain syndromes. Most are retrospective studies using data combined from all sources of pain following surgery. In the best existing population-based study of long-term outcomes, Macdonald et al found that 7-12 years post-surgery, 52 percent of women who had PMPS at four- year follow-up still had PMPS; these women had a significantly lower quality of life compared with those women whose PMPS had resolved.

Treatment of chronic post-mastectomy pain

There are very few randomized, double-blind, placebo-controlled trials of treatments for chronic pain following breast cancer surgery.

Non Pharmacological treatments

Non Pharmacological treatments like TENs and acupuncture may offer some symptomatic pain relief. In addition,  a rehabilitative approach with a focus on gentle exercise, coping and pacing strategies and relaxation techniques have been shown to help patients manage their pain better.

 

Psychological treatments

Although multidisciplinary treatment – which includes psychological interventions and physical therapy as well as medical and interventional treatments – has not been studied in patients following breast cancer surgery, it has very well established efficacy in the treatment of other chronic pain syndromes. Indeed, patients with metastatic carcinoma of the breast treated with group therapy with or without self-hypnosis training reported significantly less pain and suffering compared to control patients over the course of 1 year.

Anti neuropathic medications

Anti neuropathic medications are likely to be the main stay of management of in chronic neuropathic pain post breast cancer surgery. Amitriptyline has been examined in a randomized, double-blind, placebo-controlled, crossover trial of neuropathic pain following breast cancer surgery. Pain relief was significantly greater with amitriptyline than placebo. A recent study of patients with postherpetic neuralgia demonstrated that nortriptyline and amitriptyline provide equivalent analgesic benefits but that nortriptyline is better tolerated. A recent randomized, double-blind, placebo-controlled, crossover trial failed to find a significant benefit of venlafaxine versus placebo on the primary endpoint.

Interventional treatments for post-mastectomy pain

Trigger point injections

Injection of local anaesthetic and steroid at the points of maximal tenderness can relieve chronic post mastectomy pain. Approximately 1 in 5 patients will need a repeat injection in approximately 6 months.

Intercostal nerve blocks

Intercostal nerve block and pulsed radiofrequency ablation of the nerve under ultrasound guidance can be used in patients who do not respond to simpler treatments.

Serratus plane block (SPB)

SPB is a novel peripheral nerve block technique first described in 2013 by Blanco et al to provide analgesia for breast and thoracic wall surgeries. Lateral and anterior cutaneous branches of the second to sixth intercostal nerves pierce the external intercostals and serratus anterior in the anterior-to-mid axillary line. SPB involves deposition of local anesthetics in a plane that is superficial to or deep underneath the serratus anterior muscle in the mid-axillary line between the fourth and fifth ribs. This technique achieves blockade of sensory nerves through the axillary compartment. SPB is surely effective for the T2 intercostobrachial nerves, which play an important role in the pathology of chronic post-mastectomy pain. Pectoral nerves (PECS) II block was introduced as a deposition of local anesthetics in 2 layers, with one layer located between the intercostal and serratus anterior muscles and the other between the pectoralis major and minor at the level of the third and fourth ribs. Both SPB and PECS II blocks provide some degree of analgesia in the anterolateral thoracic wall, similar to the transversus abdominis plane blocks that are effective for somatic pain management of the anterolateral abdominal wall. Although SPB has been described as a progression from the PECS II block, it has not yet been proven as an effective treatment for chronic post breast surgery pain or more advantageous than the PECS II block.

Botox injections

Botox injections under ultrasound guidance targeting the pectoral muscles, latissimus dorsi and serratus anterior muscles can help in the management of chronic post breast surgery pain. Breast reconstruction often involves the positioning of a temporary expander implant between layers of the chest muscle, which is then filled with water to create a pocket where a permanent implant will reside. Pain can result from muscle contractions and spasms in response to the tissue expansion. Botox injections could offer relief by temporarily paralyzing the muscle so that fewer spasms occur, thereby reducing pain and discomfort.

Pulsed radiofrequency of dorsal root ganglion

Pulsed RF of the DRG has been shown to be superior to both medical management and pulsed RF of the intercostal nerve in the treatment of patients suffering from chronic post-surgical chest pain. However, given the inherent risk of performing thoracic interventional procedures, it cannot be recommended it as a first-line treatment and should be reserved for those patients refractory to pharmacotherapy. The mode of action of pulsed RF is not understood, but may include inhibition of excitatory C-fiber responses by repetitive, burst-like stimulation of A-delta fibers, global reduction of evoked synaptic activity, and minor structural changes in nerve tissue elicited by alterations in the function of the blood-nerve barrier, fibroblast activation and collagen deposition. Which, if any, of these effects plays the dominant role in analgesia is not known.

 

Summary

Chronic pain post breast cancer surgery affects nearly half the number of patients who undergo surgery for breast cancer and adversely affects their functioning. The etiopathogenesis, risk factors, natural history and effective treatments still remain areas of active research as there is little consensus in the existing literature about these issues. Prospective studies on larger populations of breast cancer survivors are required to address the existing lacunae in knowledge. Treatments including trigger point injections, botox injections and pulsed radiofrequency ablation of intercostal nerve and thoracic DRG should be considered in patients who do not respond to conservative management.

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