Post-Mastectomy Pain Syndrome Following Breast Cancer Treatment: A Neuroimmune Disorder from an Integrative Oncology Perspective

Kathy M. Mahalati MD*, John O. Collins MD, Douglas L. Forman MD

Department of Obstetrics and Gynecology, University of Maryland Medical Systems, USA Dupont Integrative Neurological Center/ Fort Wayne NeuroCenter Associates, USA Department of Plastic Surgery, Georgetown University School of Medicine and Department of Plastic and Reconstructive Surgery, John Hopkins University, USA

^*Correspondance to: Kathy M. Mahalati 

 PDF  Full Text Review Article | Open Access

Abstract:

Post-mastectomy pain syndrome (PMPS) is a common and often disabling complication of breast cancer treatment that may persist long after surgical recovery and substantially impair quality of life among survivors. Recent estimates suggest that PMPS affects approximately 20–68% of women following breast surgery, with significant long-term consequences for physical functioning, sleep quality, emotional well-being, and participation in daily activities [1-3]. Historically, PMPS has been conceptualized primarily as a localized postsurgical neuropathic condition resulting from peripheral nerve injury sustained during breast surgery [4]. However, growing evidence indicates that persistent pain following mastectomy reflects a more complex and enduring condition that extends beyond peripheral nerve damage alone. Sustained immune activation, chronic neuroinflammation, microglial dysregulation, central sensitization, and altered neuroendocrine stress-response signaling appear to play central roles in pain persistence, consistent with mechanisms described in chronic postsurgical and cancer-related pain states [5-7]. From an integrative oncology perspective, PMPS may be more accurately understood as a neuroimmune disorder arising from the convergence of peripheral nerve injury, persistent inflammatory signaling, disruption of the local tissue microenvironment following surgery or radiation therapy, and maladaptive central nervous system plasticity [2,3,8]. Drawing on contemporary literature from pain neuroscience, immunology, neuroendocrinology, and cancer survivorship research, this article synthesizes key biological mechanisms implicated in persistent post-mastectomy pain. These include cytokine-mediated nociceptor sensitization, microglial activation and glial–neuronal crosstalk, impaired neural repair processes, autonomic nervous system dysregulation, and sleep disturbance, all of which contribute to pain chronification [5,8-10]. By integrating these mechanisms within a unified neuroimmune framework, this review provides a clinically relevant conceptual foundation for mechanism-informed, multimodal, and opioid-sparing approaches to PMPS management [6,11]. Reframing PMPS in this manner may help guide future research priorities, inform clinical innovation, and support the development of individualized, integrative strategies that more fully address the multidimensional biological and psychosocial burden of chronic pain in breast cancer survivorship [3,12].

Keywords:

Post-mastectomy pain syndrome; Breast cancer survivorship; Neuroimmune dysregulation; Central sensitization; Integrative oncology; Multimodal pain management; Opioid-sparing strategies

Cite the Article:

Mahalati KM, Collins JO, Forman DL. Post-Mastectomy Pain Syndrome Following Breast Cancer Treatment: A Neuroimmune Disorder from an Integrative Oncology Perspective. Ann Clin Case Rep. 2026; 11: 2825..