Version July 2025
INTRODUCTION —
Postmastectomy pain syndrome (PMPS) is a type of chronic neuropathic pain disorder that is likely caused by damage to nerves in the chest wall or axilla during the surgical treatment of breast cancer [1-3].
Pain can be severe enough to cause long-term disabilities and interfere with sleep and performance of daily activities including use of the affected arm, leading to shoulder adhesive capsulitis (frozen shoulder) or complex regional pain syndrome (causalgia) [2]. Altered sensation can also be observed within the distribution of the injured nerve, although it may not be as debilitating as chronic pain [2]. The pain can also seriously affect the patient's mood, functional mobility, and severely impact quality of life [4]. (See "Frozen shoulder (adhesive capsulitis)" and "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis".)
The clinical manifestations and diagnosis of PMPS are discussed here. Its treatment and prevention are discussed in another topic. (See "Postmastectomy pain syndrome: Risk reduction and management".)
DEFINITION —
The definition of PMPS has not been standardized.
●The current definition for PMPS used by the International Association for Study of Pain is "chronic pain in the anterior aspect of the chest, axilla, shoulder, and/or upper half of the arm beginning after mastectomy or quadrantectomy and persisting for more than three months after surgery" [5].
●The time frame to diagnose PMPS is widely debated; three to six months of pain is generally agreed upon. A systemic review of PMPS suggested that six months of neuropathic pain that occurs at least 50 percent of the time should be used for PMPS research to create uniformity in future studies [4,6].
●The author of this topic defines PMPS as pain persisting for more than six months after breast surgery.
PATHOPHYSIOLOGY —
Many experts believe that PMPS is caused by injury to the intercostobrachial nerve (ICBN) [7,8]. The breast parenchyma and overlying skin are innervated by the anterior and lateral cutaneous branches of intercostal nerves T3 to T6 (figure 1). The ICBN is the lateral cutaneous branch of the second intercostal nerve, which emerges through the serratus anterior muscle and reaches the axilla and inner arm area to provide cutaneous sensation [9]. The ICBN is frequently injured during axillary dissection, both directly (stretch, compression, transection), and indirectly (subsequent inflammation and fibrosis, formation of a traumatic neuroma or scar tissue) [10]. Additionally, breast cancer operations can damage the brachial plexus, long thoracic, and medial and lateral pectoral nerves that innervate the breast, chest wall, and ipsilateral extremity (figure 2 and figure 3 and figure 4) [11-13].
Surgical procedures in the upper outer quadrant of the breast and the axilla can injure nerves in the operative field [14]. Axillary node dissection or retraction during mastectomy may lead to inflammation and nerve damage, resulting in pain sensations [11,15]. In addition, local radiation treatments and neurotoxic systemic therapy (eg, taxanes, platinum agents, vinca alkaloids) may also exacerbate PMPS [12,15-19]. (See "Postmastectomy pain syndrome: Risk reduction and management", section on 'Preservation of axillary nerves'.)
Different types of sensory disturbances (eg, tingling, burning, numbness) can then result from nerve injury [4,20].
INCIDENCE —
The overall incidence of nerve injury or impairment and resultant chronic pain following a breast cancer operation ranges from 20 to 72 percent [1,3,4,8,10,12,13,16,21-32]. This wide variation can be partly explained by discrepancies in terms of definitions used to ascertain PMPS, timing of assessment, or age group of the population studied [1,8,10].
The incidence of PMPS may also be underestimated since there may be multiple barriers for patients to report their pain to their physicians. Some of these reasons may include [33,34]:
●Expectation that surgery should result in pain
●Fear that persistent pain may be a sign of cancer recurrence
●Fear of bothering their physicians
●Fear their physicians may become annoyed at them
●Fear that if they complain about pain, this might take their physician's focus off of discussions about cancer surveillance and prognosis
RISK FACTORS —
Based upon retrospective and prospective studies [2,4,10,35-38], the most common variables associated with a higher risk of developing PMPS include:
Acute postoperative pain — Severe acute postoperative pain is a risk factor for developing chronic pain [16,19,35,36,39-43]. In a multivariate analysis of 537 breast cancer patients followed for one year after surgery, patients with moderate-to-severe acute postoperative pain were more likely to develop persistent pain compared with patients with less intense postoperative pain (odds ratio [OR] 2.8) [42].
Acute postoperative pain is a consistent modifiable risk factor for PMPS [6,31]. Therefore, attention to perioperative analgesia is an increasingly important opportunity to reduce the incidence of PMPS. Enhanced recovery after surgery (ERAS) pathways resulting in decreased postoperative pain scores should be considered [44-46]. Currently, the author uses a protocol which includes (see "Postmastectomy pain syndrome: Risk reduction and management", section on 'Preventive analgesia'):
●Preoperative administration of oral gabapentin (afternoon before and morning of surgery) and acetaminophen (morning of surgery).
●Perioperative administration of regional nerve blocks (pectoral blocks type 1 and 2) with liposomal bupivacaine after induction of general anesthesia.
●Intraoperative administration of 5-level pectoral intercostal fascial nerve blocks and serratus nerve blocks once breast is removed off the chest wall.
●For patients under age 40, or those with pre-existing anxiety/depression, intraoperative ketamine given as either a single dose (0.5 mg/kg) or continuous low dose infusion of ketamine (0.25 mg/kg/hr) to be turned off at least one hour prior to the end of surgery
●Intravenous ketorolac when medically appropriate.
●Postoperative administration of gabapentin around the clock for up to seven to ten days after surgery.
Younger age at diagnosis — Many studies show increased odds of persistent pain with younger age [4,10,16,32,35-38,42]. In a prospective cohort study of 174 females undergoing breast cancer surgery, the incidence of PMPS at six months was higher in those >40 than those <40 years (relative risk [RR] 5.23, 95% CI 1.11-24.64) [38]. The definitions of "younger” age in the literature vary from <35 years to <50 years [4,30,38,47].
The mechanism through which younger age represents a risk factor for PMPS is not well understood. It is possible that younger patients tend to present with higher-grade tumors and may undergo more aggressive treatments including surgery and adjuvant therapies, which may influence the prevalence of chronic pain following breast cancer treatment [15]. Other possible explanations include a reduction in sensitivity of pain receptors in older women [20,48] and increased nerve sensitivity in younger patients [43,49].
Higher body mass index — Several studies have found that the odds of developing chronic pain after mastectomy are associated with higher body mass index (BMI) [40,50-52].
●A retrospective Netherlands study of 492 patients who underwent breast cancer surgery found that 35 percent had persistent pain at six months. Multivariate analysis demonstrated that both age (p <0.01) and BMI (p = 0.04) remained independently predictive. The OR for PMPS increased with every one-point increase in BMI [51].
●In a separate study that evaluated outcomes from the Women's Healthy Eating and Living (WHEL) study of 3088 females, baseline BMI was associated with an increased risk of PMPS at four years of follow-up (OR 1.07, 95% CI 1.05-1.10). Similar to the Netherlands study, after adjusting for baseline BMI, every one-point increase in BMI was associated with an increase in PMPS (OR 1.10, 95% CI 1.04-1.16). Pooling estimates from the WHEL and eight additional studies, the meta-analysis suggested a linear relationship between every one point increased in BMI and persistent pain (OR 1.05, 95% CI 1.02-1.07) [52].
Axillary radiation — Neuropathic pain is frequently identified in patients undergoing postoperative breast/axillary radiation treatments and can occur months to years after treatment [10,12,15-19,33,40,50]. Radiation fibrosis and chronic inflammation can cause nerve entrapment and restricted shoulder movement.
●In a Danish cross-sectional questionnaire study of 3754 females who underwent breast cancer surgery with adjuvant therapy, radiation was associated with a higher risk of PMPS (OR 1.5, 95% CI 1.08-2.07) [1].
●Another study of 295 patients who underwent radiation therapy after breast cancer surgery reported that the most common complication of adjuvant radiation was breast pain (62.1 percent). Additionally, a boost dose of radiation was associated with an increased risk of pain (p = 0.013) [53].
Axillary lymph node dissection — Breast cancer surgery usually involves the breast parenchyma (mastectomy or lumpectomy), axilla (axillary lymph node dissection [ALND] or sentinel lymph node biopsy [SLNB]), and possible reconstruction.
●Breast surgery – In a review of 611 patients, surgical treatment approach toward the breast, such as partial mastectomy (n = 458) or total mastectomy, or one (n = 420) or multiple breast procedures, was not associated with PMPS [54]. Surgical factors and complications, including reoperation and bilateral surgery as well as incidence of seroma, hematoma, cellulitis, or lymphedema, also did not appear to be significant contributors [55].
●Axillary surgery – Patients undergoing a standard ALND frequently have chronic neuropathic symptoms, while a less extensive axillary surgery (ie, SLNB) is associated with less frequent chronic pain complications [15,16,35,37,48-50,56,57]. As an example, a European Organization for Research and Treatment of Cancer Quality of Life Questionnaire survey of 317 breast cancer patients found that more women undergoing an ALND with breast surgery (n = 105; ie, mastectomy or partial mastectomy) had chronic pain compared with women not undergoing an ALND (51 versus 23 percent) [15]. Some patients not undergoing an ALND did undergo an SLNB. A prospective cohort study of 174 patients undergoing breast cancer surgery found that those who underwent ALND with more than 15 nodes excised had a higher risk of PMPS (RR 2.01, 95% CI 1.08-3.75) [38].
●Reconstructive surgery – With regards to breast reconstruction, a meta-analysis published in 2020 revealed no significant difference between the prevalence of persistent pain after mastectomy alone versus mastectomy and reconstruction [58].
This may be due to more aggressive preemptive analgesic techniques [11] or the adoption of new implant-based techniques using acellular dermal matrices and prepectoral breast reconstruction (PBR) in the modern era of breast reconstruction. A meta-analysis comparing outcomes of prepectoral versus subpectoral breast reconstruction (SBR) found that PBR resulted in fewer complications and fewer PMPS compared with SBR [59]. (See "Implant-based breast reconstruction and augmentation", section on 'Surgical techniques'.)
Psychosocial factors — Patients undergoing breast cancer surgery have particularly high levels of preoperative anxiety and depression, key risk factors for the development of PMPS [25,26]. Persistent PMPS is associated with several psychosocial factors (eg, anxiety, depression, sleep disturbance, catastrophizing, somatization) [16,32,36,37,56,60,61]. In a cross-sectional cohort study of 611 patients who had a total or partial mastectomy more than six months prior to the telephone interview, 32.5 percent reported a clinically relevant pain severity of ≥3 out of 10 in the breast (34.3 percent), axilla (19.9 percent), side (8.6 percent), or arm (8.2 percent) [54]. Patients with PMPS pain ≥3 out of 10 were significantly more likely to report anxiety, depressive symptoms, sleep disturbance, somatization, catastrophizing, and perceived stress compared with women who had no PMPS.
Preoperative pain — A number of studies have demonstrated a significant association between preoperative pain and the development or severity of persistent pain several months to a year following surgery [16,37,61].
●In a clinical prediction model using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231), preoperative pain in the surgical area was associated with not only more severe acute postoperative pain but also persistent pain [56]. It has been hypothesized that pain sensitivity and/or central sensitization may increase the susceptibility to persistent pain after surgery.
●In a separate prospective, longitudinal study, 96 percent of females with preoperative pain developed persistent postsurgical pain, compared with 55 percent of those who did not have preoperative breast pain in a six-month follow-up period [62].
Smoking — A potential association of smoking with PMPS has also been found in several studies [10,37]. In a prospective study of 200 patients who underwent breast cancer, PMPS was observed with a rate of 31.6 percent. A statistically significant relationship was found between smoking and PMPS, with 27 of 30 patients who smoked (90 percent) developing chronic pain [37]. Nicotine in tobacco products has been found to play a critical role in pain-related pathophysiology. Long-term exposure leads to the development of tolerance and increased pain sensitivity [10].
Reduced physical activities — Some researchers have also reported an association between reduced physical activity and the development of PMPS [55,63]. A prospective observation cohort study reported that adequate physical activity reduced the intensity of pain, depression, and anxiety symptoms in females affected by PMPS at both three and six months after surgery [63].
CLINICAL FEATURES
Clinical manifestations
Patient presentation — Patients with PMPS typically present with burning, electric shock, or stabbing pain and/or neuropathic symptoms (eg, numbness, hyperesthesia, paresthesia) at the operative site and/or the ipsilateral arm [4,8,10]. Other symptoms include chest wall muscle pain, decreased muscle strength, and reduced range of motion of the shoulder [33,34,64,65].
A discussion on the critical components of the history for assessing chronic pain is reviewed separately. (See "Evaluation of chronic pain in adults", section on 'Neuropathic pain'.)
Physical examination — The pertinent findings on the physical examination include sensory changes (eg, hypersensitivity, hyposensitivity) at the operative site and/or ipsilateral extremity and decreased range of motion and strength in the ipsilateral arm [64]. For example, intercostobrachial neuralgia pain is typically accompanied by altered sensation in the distribution of the intercostobrachial nerve (axilla, lateral chest, and medial aspect of the arm), whereas neuroma pain is found in the region of the scar, which can be provoked by percussion.
In addition to sensory alterations, nerve impairment can result in decreased shoulder strength and range of motion. Methodological differences have resulted in a wide range of reported incidences, ranging from 2 to 51 percent for impairments in range of motion that interfered with normal daily activities and 17 to 33 percent for decreased muscle strength [64,65].
Radiographic studies — There are no specific radiographic findings for PMPS. In the clinical setting of pain confined to the breast, a mammogram, an ultrasound, or magnetic resonance imaging (MRI) may identify a fluid collection or evidence of recurrent disease. A plain film of the shoulder and humerus can identify local abnormalities such as a fracture, arthritic changes, metastatic disease, or benign bone cysts.
Laboratory studies — There are no specific laboratory findings for PMPS. Abnormal laboratory tests (eg, blood count, serologic markers of inflammation, cancer markers) may signify other causes of pain such as rheumatologic, infectious, or oncologic etiologies.
Neurophysiologic testing — Neurophysiologic testing, principally nerve conduction studies and electromyography, are frequently employed in suspected disorders of the peripheral nervous system but are not commonly used in PMPS, which remains a clinical diagnosis.
DIAGNOSIS —
The diagnosis of PMPS is made based upon characteristic symptoms of a burning, electric, or stabbing pain or paresthesia in the chest wall, axilla, and/or ipsilateral extremity following a breast cancer operation and/or local radiation therapy or chemotherapy, in the absence of an infection or recurrent disease [4,8].
The physical examination includes a breast, chest wall, and axillary examination that identifies post-treatment changes (ie, surgical, radiation) in the absence of signs of local recurrence or infection. A detailed sensory and motor neurologic evaluation of the affected sites reveals motor and/or sensory deficiencies in the distribution of the affected peripheral nerve (eg, intercostal brachial, long thoracic, thoracodorsal nerves).
Imaging studies are not necessary or useful for making the diagnosis of PMPS. However, if there is diagnostic uncertainty, imaging studies can be helpful in excluding other disorders in differential diagnosis.
DIFFERENTIAL DIAGNOSIS
●Locoregional recurrent breast cancer – Pain is not a common presenting symptom for a local recurrence of breast cancer. A locoregional recurrence is typically identified on the physical examination as a palpable mass or as an abnormality on an imaging study, such as a mammogram. (See "Clinical manifestations and evaluation of locoregional recurrences of breast cancer".)
●Metastatic breast cancer – Bones are a common site of metastasis from breast cancer [66]. Bone pain from metastatic disease is severe and debilitating and results from destruction of bone tissue. Localized bone pain may indicate a fracture or impending fracture at the site of disease. Diagnosis can be made by imaging studies. (See "The role of local therapies in metastatic breast cancer".)
●Breast inflammation/infection – Pain can accompany erythema in noninfectious breast disorders, such as postirradiation mastitis, superficial thrombophlebitis, or cellulitis and abscess. An abscess can also occur in the axilla following an axillary dissection. Infection as a cause of postmastectomy breast pain typically occurs early in the postoperative course. (See "Nonlactational mastitis in adults".)
●Phantom breast pain or phantom sensations – Chronic pain or chronic sensations can develop as phantom symptoms following a total or partial mastectomy, similar to those that occur after a limb amputation. The postsurgical nonpainful sensations are called phantom breast sensations (PBSs), while a painful sensation is called phantom breast pain (PBP). While the symptoms of PBP are similar to those of PMPS, subjectively, patients with PBP report the persistence of sensations within their amputated breast.
•PBS includes all sensations that are experienced in the amputated breast, whereas PBP includes sensations so intense that they are experienced as pain [67]. The prevalence of PBS and PBP ranges from 0 to 66 percent, with the wide range most likely attributed to differences in methodologies [2,15,67]. PBSs are characterized by a sensation of persistence of the removed breast after its removal. PBSs are distinguishable from pain or other sensory disturbances in or around the scar.
•PBP is characterized by disturbing and painful sensations in the area of the nipple alone or involving the entire breast or segment that was resected and may persist for years after the operation. The etiology includes central nervous system sensitization and cortical reorganization, which are associated with nerve damage and are considered to have a role in pain chronification [15]. The injury to neurons results in spontaneous and evoked hyperexcitability. Psychological factors have also been implicated.
●Chemical neuropathy – Chemotherapeutic agents (eg, taxanes, platinum based) can produce peripheral neuropathies. The presentation includes a distal, symmetric distribution of pain and/or paresthesia. Electrodiagnostic testing and clinical presentation help establish the diagnosis. (See "Overview of polyneuropathy", section on 'Toxic'.)
●Lymphedema – Lymphedema can present as an insidious soft tissue enlargement of the hand and arm. It can occur as a result of injury from an axillary dissection and/or radiation therapy or from obstruction of the lymphatic channels (eg, tumor cells, mass effect). Discomfort and the sensation of heaviness is the most common presenting symptom, rather than pain. (See "Clinical features, diagnosis, and staging of peripheral lymphedema".)
●Musculoskeletal disorders – Common musculoskeletal disorders, such as bursitis, adhesive capsulitis (frozen shoulder), tendonitis, or rotator cuff injury, can present with shoulder pain and a limited range of motion. Diagnosis can be established based on the history, clinical examination, and radiographic imaging (eg, MRI). (See "Evaluation of the adult with shoulder complaints".)
●Cervical radiculopathy – Cervical radiculopathy can present with pain; paresthesia; numbness; or weakness of the shoulders, arms, or hands [66]. The onset of symptoms is most frequently acute when caused by a herniated nucleus pulposus but may be more indolent when due to spondylosis. Imaging studies, electrodiagnostic studies, and the clinical presentation can help establish the diagnosis. (See "Clinical features and diagnosis of cervical radiculopathy".)
QUALITY OF LIFE —
Quality of life (QoL) is a multidimensional term that includes the physical, social, and psychological well-being domains. For a cancer patient, the appearance of pain may represent a continuous memory of the treatment and the disease. Additionally, pain may be incorrectly viewed as a sign of recurrent cancer and cause considerable psychological distress and a poor QoL, even in the absence of disease [6,15,64,68]. (See "Assessment of cancer pain" and "Overview of cancer pain syndromes".)
PMPS has been found to exert a significantly negative impact on the overall QoL, even in patients in whom its severity is mild [6]. PMPS may limit the range of motion of the upper extremities, which would negatively impact the capacity to perform daily tasks and even basic occupational tasks [64]. Furthermore, PMPS has been found to take a significant toll on mental health, emotional well-being, and social relationships [68].
SUMMARY AND RECOMMENDATIONS
●Pathophysiology – Postmastectomy pain syndrome (PMPS) is a chronic neuropathic disorder caused by direct nerve injury (eg, transection, compression, ischemia, stretching, retraction) during the breast cancer operation or the subsequent formation of a traumatic neuroma or scar tissue and possibly exacerbated by local radiation treatments and neurotoxic chemotherapies (eg, taxanes). (See 'Pathophysiology' above.)
●Clinical presentation – Patients with PMPS typically present with burning, electric shock, or stabbing pain and/or neuropathic symptoms (eg, numbness, hyperesthesia, paresthesia) at the operative site and/or the ipsilateral arm. Other symptoms of patients with PMPS include chest wall muscle pain, reduced range of motion of the shoulder, and reduced shoulder and/or hand grip strength. (See 'Patient presentation' above.)
●Physical findings – The pertinent findings on the physical examination include sensory changes (eg, hypersensitive, hyposensitive) at the operative site and/or ipsilateral extremity and decreased range of motion and strength in the ipsilateral arm. (See 'Physical examination' above.)
●Diagnosis – The diagnosis of PMPS is made based upon symptoms of a burning, electric, or stabbing pain or paresthesia in the chest wall, axilla, and/or ipsilateral extremity following a breast cancer operation and/or local radiation therapy or chemotherapy, in the absence of an infection or recurrent disease. (See 'Diagnosis' above.)
●Differential diagnosis – The differential diagnosis for PMPS includes recurrent breast cancer, metastatic breast cancer, benign inflammatory disorders, and postradiation and chemotherapy effects. (See 'Differential diagnosis' above.)
