Optimal Management of Post-mastectomy Pain Syndrome

Between 25% and 60% of women develop chronic neuropathic pain after mastectomy, a condition known as post-mastectomy pain syndrome.

Between 25% and 60% of women develop chronic neuropathic pain after mastectomy, a condition known as post-mastectomy pain syndrome (PMPS).¹

Pain associated with PMPS manifests in the anterior thorax, axilla, and/or upper arm and is hypothesized to result from damage to major peripheral nerves during surgery.² The pain typically starts shortly after surgery and persists for at least 3 to 6 months.^1,2 However, the clinical picture of PMPS is highly heterogeneous, which has complicated efforts to standardize its definition and management.^1,2 PMPS may not arise for several months after surgery, may occur after breast surgeries other than mastectomy, and may resolve within a few years or last a decade or longer.^1-3 What is consistent about PMPS is the negative effect it has on sufferers’ qualify of life.³

Despite widespread recognition of PMPS, data suggest it often goes untreated or undertreated.⁴One reason for inadequate management of PMPS may be the lack of quality information about optimal treatment.^1,4

Recently, researchers from Denmark reviewed the literature to assess whether sufficient data existed to identify a safe and reliable treatment for PMPS.¹ Of 88 relevant studies identified in the PubMed database, only 6 satisfied the authors’ criteria for inclusion. Treatment modalities evaluated in the eligible studies included antidepressants (amitriptyline or venlafaxine), an antiepileptic (levetiracetam), topical capsaicin, and autologous fat grafting. None of the studies included assessed the effects of analgesics such as nonsteroidal anti-inflammatory drugs, which a survey of Japanese breast cancer specialists found were the most commonly used treatment for PMPS.⁴

Amitriptyline is a tricyclic antidepressant routinely prescribed to treat various types of neuropathic pain, including PMPS. In a randomized controlled trial (RCT), which Magdalena Larsson, MD, from the Department of Plastic Surgery, Odense University Hospital, Denmark, and colleagues reviewed, a 4-week-long amitriptyline treatment was effective in reducing neuropathic pain in the arms and in the vicinity of the breast scar significantly more than placebo (P <.05). In another RCT, the serotonin-norepinephrine reuptake inhibitor venlafaxine significantly decreased average and maximum pain intensity (P <.05), but did not significantly reduce average daily pain intensity. The levetiracetam RCT found the antiepileptic drug had no significant effect on PMPS pain at doses of up to 3 g/day.

A RCT of topical capsaicin (0.075%, applied 4 times per day) found significant improvement in jabbing pain (P <.05) and overall pain scores (P =.04) after 6 weeks of treatment, but no improvement in steady pain or skin pain. Of note, several patients reported an unpleasant burning sensation at the application site. Dr Larsson and her colleagues noted that “[t]he findings are in line with two other studies, which also found a significant effect of topical capsaicin on PMPS.”

Two studies in the systematic review evaluated autologous fat grafting for PMPS. Fat grafting is hypothesized to induce scar tissue remodeling, and possibly analgesia. Both studies found significant reductions in pain scores after fat grafting (P =.0005; P ≤.005), and the researchers estimated this treatment to be promising.

Summary & Clinical Applicability

Many women are affected by PMPS, yet few quality studies have evaluated optimal management for this condition. Some evidence suggests antidepressants, topical capsaicin, and fat grafting offer pain relief, but In the absence of supporting data from larger, better-quality studies, the findings have limited applicability to practice.

Limitations & Disclosures

The systematic analysis included only 6 studies, almost all of which were small and had serious limitations. Two studies were decades-old. The 2 studies of what the authors considered a promising treatment were not randomized. Poor reporting on the methodology of several studies made it difficult for the authors to assess the quality of the data.

Nevertheless, the researchers concluded that the studies show there is “a palette of effective treatment modalities of PMPS today.”

Many physicians continue to prescribe analgesics for PMPS, yet evidence shows neuropathic pain responds poorly to analgesics.^4,5

The researchers called for larger, higher-quality studies to provide greater knowledge of PMPS and determine how to more adequately manage this debilitating condition.

References

1. Larsson IM, Sørensen JA, Bille C. The post-mastectomy pain syndrome-a systematic review of the treatment modalities [published online January 30, 2017]. Breast J. doi: 10.1111/tbj.12739
2. Waltho D, Rockwell G. Post-breast surgery pain syndrome: establishing a consensus for the definition of post-mastectomy pain syndrome to provide a standardized clinical and research approach—a review of the literature and discussion. Can J Surg. 2016;59:342-350. doi: 10.1503/cjs.000716
3. Macdonald L, Bruce J, Scott NW, Smith WC, Chambers WA. Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome. Br J Cancer. 2015;31:92:225-230. doi: 10.1038/sj.bjc.6602304
4. Kojima KY, Kitahara M, Matoba M, Shimoyama N, Uezono S. Survey on recognition of post-mastectomy pain syndrome by breast specialist physician and present status of treatment in Japan. Breast Cancer. 2014;21:191-197. doi: 10.1007/s12282-012-0376-8
5. Galluzzi KE. Management of neuropathic pain. J Am Osteopath Assoc. 2015;105;S212-S19.