Exploring biomarkers for (persistent) pain following breast cancer treatment

Breast cancer is the most commonly diagnosed cancer in women. Many patients experience treatment-related side effects, with pain affecting up to 40% of breast cancer patients during treatment. Pain is therefore a major concern that can severely decrease the quality of life. While it is temporary, persistent pain can continue long after treatment has ended, affecting up to 50% of breast cancer patients. Research has shown that the development and maintenance of pain is multifactorial, influenced by a combination of biopsychosocial factors rather than treatment alone. To better understand how pain evolves from no pain at diagnosis to persistent pain following treatment, objectively measurable factors or ‘biomarkers’, may track the individual’s pain progression and enable more personalized pain management. Unfortunately, there are currently no approved clinical biomarkers for pain. Previous studies in non-cancer populations suggest brain imaging, cytokines, somatosensory functioning, and psychosocial factors as potential pain biomarkers, but their role in breast cancer remains unclear. This doctoral thesis aimed to: 1) systematically review the existing evidence regarding morphological, functional, and structural as well as cytokine alterations in cancer patients and survivors experiencing persistent pain; 2) investigate candidate early risk and prognostic biomarkers for pain maintenance following breast cancer surgery; and 3) identify perioperative biopsychosocial phenotypes and their relationship with long-term pain outcomes. This doctoral thesis provides new insights into how brain imaging, cytokines, somatosensory functioning, and psychosocial distress play a role in breast cancer treatment-related pain. The systematic reviews revealed that research regarding brain imaging and cytokines in cancer patients with persistent pain is limited, with notable gaps. Our exploratory studies addressed some gaps and served as an important step to build on. IL-6 emerged as the most promising biomarker with accumulating evidence supporting its role in the development and maintenance of pain, but further validation is warranted. This research highlights the importance of longitudinal designs that track the full pain chronification trajectory in breast cancer patients. Standardized pain assessment tools, including consistent cut-off scores and time frames, are recommended to strengthen research comparability. Moreover, clinicians should be aware of patients’ mental health throughout treatment trajectory to reduce psychosocial distress and potentially prevent long-term pain. In conclusion, this thesis provided a novel interdisciplinary approach to identify candidate pain biomarkers in breast cancer patients. It demonstrated early evidence that brain imaging, cytokine levels, somatosensory functioning, and psychological distress hold promise as pain biomarkers.