Persistent pain after breast cancer surgery (PPBCS) is both common and debilitating, lasting months to years after surgery, a mainstay treatment of breast cancer. The current body of PPBCS evidence has focussed on identifying clinical, psychological and treatment related risk factors however, emerging evidence suggests that genes and pain processing may also contribute. Incorporating these factors when analysing risk factors may improve our ability to identify patients at risk of PPBCS and give insight into how PPBCS develops. Given that PPBCS persists after surgery, it may be that expression of known pain genes may pay a role in how the pain develops.
Breast cancer is the largest cancer in New Zealand women however, there has been a little research on PPBCS from New Zealand. As such, this research sought to address two problems. Firstly, the prevalence and impact of PPBCS in a New Zealand population was estimated and risk factors (clinical, demographic, psychological, pain processing and inherited (genetic)) for PPBCS development in this population were identified. Secondly, an assessment of gene expression from before surgery to 6 months after surgery was conducted for previously identified pain genes to provide some insight into how PPBCS may develop.
Dr D L C Chiang
Assoc Prof M T Kluger
Assoc Prof N A H Helsby
Assoc Prof D A Rice
Assoc Prof A A Somogyi
The project was awarded two-year funding of $A133,396 through the ANZCA research grants program for 2018 and 2019.
This research project followed a cohort of patients over a 6-month period from before surgery to 6 months after surgery. They evaluated patients during this time using validated questionnaires that assessed pain intensity, quality and interference, upper limb function and psychological distress. Blood was taken for genomic analysis and patient pain processing was assessed.
Approximately 39% of patients reported ongoing pain at 6 months after surgery with 15% of all patients reporting this pain as moderate to severe. Moderate to severe pain was associated with greater pain interference, greater upper limb dysfunction and greater psychological distress.
Risk factors were identified, and these include moderate to severe pain (at any anatomical site) before surgery, greater psychological distress at day 14 after surgery and the COMT rs6269 GA genotype. General anaesthesia employing a total intravenous propofol infusion was found to be protective for the condition. The team are completing the analysis (and have a paper in draft) of gene regulation and expression over this 6-month period and will provide the foundation with the article once published.
This research has been presented to the New Zealand breast cancer society, NZ pain society, ANZCA, Physiotherapy NZ, and various hospitals in Singapore and Vancouver. The paper has raised awareness about the problem amongst treating clinicians, patients, and researchers. Currently, PPBCS is a poorly managed and under-recognised condition. Increased awareness may result in an increased discussion between patients and physicians leading to improvements in management.
The risk factor analysis from this study identified risk factors within entire perioperative period (from before surgery to 6 months after surgery) to PPBCS development. These included genetic, pain and psychological factors, making it clear that factors of different modalities all contribute to PPBCS development. This finding has led to the development of a care protocol for breast cancer patients that addresses biological, psychological, and social concerns throughout the 6 month period to reduce the number of patients affected by PPBCS. The effectiveness and feasibility of this protocol will be evaluated by a randomised control trial.
Gene expression is regulated through multiple processes (such as DNA methylation) which can be influenced by multiple environmental factors, such as surgical inflammation, medications and psychological distress. The team are currently completing the final analysis of the gene regulation and expression exploratory studies. Preliminary data suggest that DNA methylation of the COMT gene may increase over the 6-month period in a manner which is dependent on the patient’s genetic makeup. They are in the process of determining if these changes result in changes to gene expression. This is important as associations between the COMT gene and chronic post-surgical pain have been inconsistent. This finding may contribute to explaining this inconsistency.
Journal Articles
Chiang DLC, Rice DA, Helsby NA, Somogyi AA, Kluger MT. The incidence, impact, and risk factors for moderate to severe persistent pain after breast cancer surgery: a prospective cohort study. Pain Medicine 2023, 24(9):1023-1034
Chiang DLC, Burns K, Rice DA, Somogyi AA, Kluger MT, Helsby NA. Longitudinal changes in DNA methylation of COMT in patients undergoing breast cancer surgery, In draft
Conference Presentations
- Chiang, D. Persistent pain after breast cancer surgery, a New Zealand perspective. Invited speaker, Vancouver General Hospital Grand Rounds 2023, Canada
- Chiang, D. Persistent pain after breast cancer surgery: a prospective cohort study in a New Zealand population. Oral presentation, Gilbert Brown Prize Presentation ANZCA ASM 2023, Sydney
- Chiang, D. Persistent pain after breast cancer surgery. Invited speaker, New Zealand Pain Society ASM 2023, Auckland
- Chiang, D. The genetic and epigenetic influences on persistent pain after breast cancer surgery in a New Zealand population. Oral presentation, University of Auckland, School of Medicine, Doctoral Research Showcase, 2021, Auckland
Webinar
Chiang, D. Persistent pain after breast cancer surgery. Invited speaker, OPAL Webinar 2023, Physiotherapy New Zealand.