Background & Aims

Persistent Pain after Breast Cancer Treatment (PPBCT) is one of the most prevalent and debilitating morbidities affecting women after breast cancer treatment with a prevalence of 25-60% [1]. PPBCT impairs physical, psychological, and social well-being of breast cancer survivors. Known risk factors for persistent (pain)symptoms after breast cancer treatment are younger age, radiotherapy, axillary lymph node dissection, more intensive acute postoperative pain and preoperative pain, psycho-social distress and sensitization of the nociceptive system [2] [3]. Comprehensively identifying individual risk factors, including psycho-social and psycho-physical traits is an important step towards individualized prevention strategies [4] [5] [6] [7] [8].
The presented pilot-study aimed to test the feasibility of a protocol including neurophysiological, psychological, and clinical parameters for the prediction of PPBCT one year after breast surgery.

Methods

Prospective single-centre cohort of adult female patients undergoing unilateral surgery for breast cancer. Primary objective was the incidence of PPBCT [9].
The secondary objectives were pain severity, interference and disability (BPI), psycho-social distress, sensory disturbances of the operated area measured with a short version of the DFNS QST protocol [10] and central sensitization and conditioned pain modulation according to NASQ paradigm [11] assessed at baseline, 10 days, four and 12 months.
Baseline characteristics of the sample were summarized as mean and standard deviation (SD) or as count and percentage stratified by PPBCT status. If the scatterplot showed a clear difference between the presence of this factor for the different groups (PPBCT or no PPBCT), this factor was further analysed with Chi square/Fisher’s exact test, Mann-Whitney U test.

Results

Thirteen patients completed the study. The prevalence of PPBCT was 31 %. PPBCT was associated with higher BMI, un-employment, less social support, a lower health related quality of life, expected post-operative pain intensity, preoperative pain and acute post-operative pain intensity. QST revealed bilateral thermal hypesthesia and a reduction of temporal summation of pain (WUR).
The most important finding was a prominent bilateral hypersensitivity to blunt pressure of the pectoral muscle and at extraterritorial muscles at baseline. At the pectoral muscles, PPT dropped further at 10 days after surgery (p<0.01) and re-increased slowly afterwards. In the extra¬territorial sites, PPTs remained similar to baseline immediately after surgery and gradually recovered to normal values. Pressure pain hyperalgesia was more pronounced in PPBCT patients. Furthermore, CPM seemed less in PPBCT patients at baseline and 10 days after surgery.

Conclusions

Even in the small PREPARE cohort, the incidence of PPBCT was 31 % one year after surgery.
PREPARE confirms the risk factors lower quality of life, surgical fear, the presence of preoperative and intense postoperative pain [12]. QST measurements revealed a bilateral hyperalgesia to blunt pressure that was more pronounced and long-lasting in the surgical dermatomes and in patients who later developed PPBCT. These results confirm earlier observations [13] and imply wide-spread pain facilitation with a component of segmental secondary hyperalgesia. In addition, DNIC/CPM seemed to be less efficient in PPBCT patients. Reduced DNIC/CPM has been demonstrated to be predictive for severe acute postoperative pain after breast cancer surgery [14]. Altogether our limited findings point towards a combination of general supra-spinal sensitization and reduced descending noxious inhibitory control in patients developing PPBCT.

References

1.Wang, K., et al., Prevalence of pain in patients with breast cancer post-treatment: A systematic review. Breast, 2018. 42: p. 113-127.
2.Dams, L., et al., Biopsychosocial risk factors for pain and pain-related disability 1 year after surgery for breast cancer. Support Care Cancer, 2022. 30(5): p. 4465-4475.
3.Schreiber, K.L., et al., Predicting, preventing and managing persistent pain after breast cancer surgery: the importance of psychosocial factors. Pain Manag, 2014. 4(6): p. 445-59.
4.Sipilä, R., et al., Development of a screening instrument for risk factors of persistent pain after breast cancer surgery. Br J Cancer, 2012. 107(9): p. 1459-66.
5.Schreiber, K.L., et al., Preoperative Psychosocial and Psychophysical Phenotypes as Predictors of Acute Pain Outcomes After Breast Surgery. J Pain, 2019. 20(5): p. 540-556.
6.Meretoja, T.J., et al., Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery. J Clin Oncol, 2017. 35(15): p. 1660-1667.
7.Lötsch, J., A. Ultsch, and E. Kalso, Prediction of persistent post-surgery pain by preoperative cold pain sensitivity: biomarker development with machine-learning-derived analysis. Br J Anaesth, 2017. 119(4): p. 821-829.
8.Schreiber, K.L., et al., Prediction of Persistent Pain Severity and Impact 12 Months After Breast Surgery Using Comprehensive Preoperative Assessment of Biopsychosocial Pain Modulators. Ann Surg Oncol, 2021. 28(9): p. 5015-5038.
9.Schug, S.A., et al., The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain. Pain, 2019. 160(1): p. 45-52.
10.Rolke, R., et al., Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain, 2006. 123(3): p. 231-43.
11.van Helmond, N., et al., A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery. J Vis Exp, 2018(131).
12.Tan, H.S., et al., Risk factors for persistent pain after breast cancer surgery: a multicentre prospective cohort study. Anaesthesia, 2023. 78(4): p. 432-441.
13.van Helmond, N., et al., Hyperalgesia and Persistent Pain after Breast Cancer Surgery: A Prospective Randomized Controlled Trial with Perioperative COX-2 Inhibition. PLoS One, 2016. 11(12): p. e0166601.
14.Ruscheweyh, R., et al., Psychophysical and psychological predictors of acute pain after breast surgery differ in patients with and without pre-existing chronic pain. Pain, 2017. 158(6): p. 1030-1038.
15.Zomkowski, K., et al., Pain characteristics and quality of life of breast cancer survivors that return and do not return to work: an exploratory cross-sectional study. Disabil Rehabil, 2021. 43(26): p. 3821-3826.
16.Hamood, R., et al., Chronic pain and other symptoms among breast cancer survivors: prevalence, predictors, and effects on quality of life. Breast Cancer Res Treat, 2018. 167(1): p. 157-169.
17.Lukas, A. and W. Buhre, Individualized multidisciplinary analgesia to prevent persistent postsurgical pain. Curr Opin Anaesthesiol, 2022. 35(3): p. 380-384.
18.Lukas, A., et al., AMAZONE: prevention of persistent pain after breast cancer treatment by online cognitive behavioral therapy-study protocol of a randomized controlled multicenter trial. Trials, 2022. 23(1): p. 595.
19.Sipilä, R., E. Kalso, and J. Lötsch, Machine-learned identification of psychological subgroups with relation to pain interference in patients after breast cancer treatments. Breast, 2020. 50: p. 71-80.

Presenting Author

Anne Lukas

Poster Authors

Anne Lukas

MD Dr

MUMC+

Lead Author

Topics

  • Mechanisms: Biological-Systems (Physiology/Anatomy)