In this prospective, monocentric, observational study performed in a large third-level teaching hospital, we have observed a 28% [95%CI 23.1%-33.4%] incidence of CPBS in a cohort of female patients undergoing surgery for breast cancer. Axillary surgery, preoperative use of pain medications, and higher dynamic NRS values at 6hrs postoperatively have been identified as independent predictors of CPBS. The presence of early signs and symptoms of persistent pain, assessed at 2 months after surgery (“pain becoming chronic”), concords with CPBS at 3 months.
Chronic pain is a very well-known complication after breast surgery(Alves Nogueira Fabro et al. 2012; De Oliveira et al. 2014; Tasmuth et al. 1996; Wang et al. 2018). Despite the increased attention and the multidisciplinary efforts made to prevent this complication, the occurrence of persistent pain after breast surgery still remains high(Humble et al. 2018). The incidence of CPBS found in our cohort of patients (28%) falls within the range of values reported in previous studies (i.e. 25–60%(Gartner et al. 2009; Wang et al. 2018)). This wide variability in CPBS incidence mainly derives from the lack of a specific definition of CPBS, only recently provided by the IASP task force. The main significance of the present study lies in the fact that it provides estimates of the incidence of CPBS based on the IASP definition. Accordingly, in contrast with previous studies where CBPS was usually detected at 12–24 months postoperatively(Bell et al. 2014; Mejdahl et al. 2013), we have evaluated CPBS at 3-month follow-up. Furthermore, in order to avoid confounding factors or misinterpretation of signs or symptoms, each patient enrolled in this study was preoperatively taught how to correctly identify body areas (i.e. breast/anterolateral chest wall, axilla, ipsilateral arm) and symptoms of persisting postoperative pain (including neuropathic characteristics). Finally, follow-up assessment of pain at 2 months and at 3 months was carried out after the scheduled postoperative surgical and physiotherapy evaluations so as to exclude other confounding causes of persistent postoperative pain (e.g. seroma, hematoma, prosthesis infection, previous arm-shoulder pain). All these aspects have contributed to improve the reliability of CPBS incidence estimated in this study.
Interestingly, 69.8% of patients with CPBS already had signs or symptoms of persistent pain (“pain becoming chronic”) at 2 months postoperatively, while 91.9% of those without CPBS did not experienced signs or symptoms of “pain becoming chronic” at 2 months postoperatively. To the best of our knowledge, this is the first study to report a concordance between subacute pain after breast surgery and CPBS. The possibility to early detect persistent pain might help physicians to more effectively prevent pain chronicization. A follow-up assessment of persistent pain right after surgery might allow early detection of “pain becoming chronic” and favor the implementation of proactive pharmacologic and non-pharmacologic approaches to prevent CPBS, particularly in high risk patients.
There is, however, no clear consensus about the definition of “high risk patients” for CPBS, thus making it difficult to identify those subjects who might benefit the most from careful and early pain assessment. Risk stratification is currently based on the identification of those preoperative and intraoperative factors statistically associated with CPBS. We have explored these factors in our cohort of patients. In contrast with previous studies, we have not observed an association between CPBS and patients’ age(Gartner et al. 2009; Vilholm et al. 2008), previous breast surgery(Vilholm et al. 2008), reconstructive surgery(Roth 2018) or implant-device placement (both above or below the pectoralis major muscle)(Wallace et al. 1996). On the other hand, our study confirms that there is little evidence to suggest CPBS might be influenced by type of anaesthesia(Cho et al. 2013; Steyaert et al. 2016; Veevaete and Lavand’homme 2014). To the best of our knowledge, this is the first study evaluating selective pectoral muscle denervation as a potential risk factor for CPBS. Although denervation is a major risk factor for chronic neuropathic pain, we found that among the 19 patients undergoing selective pectoral muscle denervation for aesthetic purposes none developed CPBS. Independently associated factors predicting CPBS in our cohort of patients were: long-term use of analgesics for preexisting chronic pain, axillary surgery, and higher values of dynamic NRS at 6hrs postoperatively.
Preoperative breast pain and/or preexisting chronic pain before surgery are well-known risk factors for chronic postoperative pain, particularly for CPBS(Gartner et al. 2009; Wang et al. 2018). In this study, nearly a third of patients had preoperative pain, mainly low-back pain or migraine (for 52.6% and 44.2% of cases respectively). Preoperative painful conditions seem to predispose patients to the development of chronic post-surgical pain/CPBS, probably because the postoperative transition from acute to chronic pain is facilitated by long-term central and peripheral pain sensitization(Ji R, Nackley A, Huh Y, Terrando N 2018). In this study, preoperative chronic pain was not found to be an independent risk factor for CPBS, except for the most severe cases requiring chronic analgesic drugs for pain management. As far as we are aware, this is the first study reporting a correlation between the use of preoperative painkillers and CPBS. In our cohort of patients, migraine (treated with paracetamol and NSAIDs), low-back pain (treated with paracetamol, NSAIDs, and corticosteroids), and chronic dental pain (treated with NSAIDs and gabapentin) were the main causes for long-term use of analgesics.
The association between axillary surgery and CPBS has already been reported in the literature. In particular, conclusions produced from a meta-analysis study including more than 19,000 patients have highlighted a 21% increased risk of developing CPBS in those who underwent axillary surgery(Wang et al. 2018). In this study, axillary surgery was associated with a 93% increased risk of developing CPBS. A likely explanation is the use of different approaches in data collection for evaluating the correlation between axillary surgery and CPBS. A higher likelihood of nerve injury during axillary surgery, more pronounced for axillary lymph node dissection (ALND) than sentinel node biopsy, has been advocated as the most probable cause of this association. Interestingly, differences between sentinel node biopsy and ALND as risk factors for CPBS have not emerged in our cohort of patients, probably because of the low rate of ALND included in this study (15.3% vs > 30% in other studies)(Wang et al. 2018). To the best of our knowledge, no study has so far evaluated the possible role of sentinel node biopsy as a risk factor for CPBS.
Higher dynamic NRS values at 6 hours postoperatively play a role as independent factors to predict CPBS in our cohort of patients. Several studies have recognized presence and severity of acute postoperative pain as risk factors for postoperative chronic pain(Palotie et al. 2013; Tasmuth et al. 1996), particularly for CPBS(Fassoulaki et al. 2009). Our results suggest that one-point increase in dynamic NRS values corresponds to a 28% increased risk of developing CPBS. Median postoperative NRS values reported in this study, both at rest and during movement, suggest that adequate postoperative management of pain was generally achieved in the enrolled population. It is worth noting that patients who developed CPBS at 3 months exhibited higher NRS values than those who did not. In particular, statistically significant differences were observed between CPBS and No-CPBS groups in terms of dynamic and static NRS values at 3hrs, 6hrs, 12hrs and 24hrs postoperatively. In spite of statistical significance, differences in NRS values between groups had minor clinical relevance.
Pain intensity and pain interference with daily functions were assessed through the Italian validated version of the BPI questionnaire. This is a reliable multidimensional tool for evaluating also non-oncological chronic pain and has already been used for CPBS(Bonezzi et al. 2002; De Oliveira et al. 2014). Analysis of BPI scores by item showed that in most cases chronic pain was of mild to moderate intensity. In 18 (20.9%) patients with CPBS, the median NRS values recorded during movement were greater than five, therefore reflecting moderate to severe chronic pain. These results are in line with those reported in the literature (Andersen and Kehlet 2013; Leysen et al. 2018; Peuckmann et al. 2009). Finally, according to the BPI questionnaire, CPBS had a profound impact on sleep quality, mood and perception of happiness.
It is plausible that a number of limitations may have influenced the results of this study. First, this is a monocentric study carried out in a single teaching-hospital. Second, we were not able to perform preoperative psychological tests in order to evaluate psychological factors as potential predictors of CPBS. Third, we observed a relatively low incidence of preoperative chronic pain in our cohort of patients compared to the average 30% reported in the literature(McCann et al. 2012). This possible underestimation might be related to the lack of standardized screening either with a valid tool for preoperative pain assessment or with preoperative quantitative pain testing. A further limitation is that neither the numbers and levels of sentinel node biopsy nor the preservation vs cut of the intercostobrachial nerve were recorded. Finally, we were not able to evaluate the role of acupuncture and other non-pharmacologic analgesic therapies or interventional procedures in modulating CPBS.