Persistent Pain following Breast Cancer Surgery: Correlates and Determinants

Abstract

Evaluation of: Gartner R, Jensen MB, Nielsen J, Ewertz M, Kroman N, Kehlet H: Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 302(18), 1985–1992 (2009). This was a nationwide cross-sectional study of the prevalence of and the factors associated with persistent pain and sensory disturbances among 3253 women aged 18–70 years who received surgery and adjuvant therapy (if indicated) for primary breast cancer in Denmark between 1 January 2005 and 31 December 2006. Mean time from surgery to data collection was 26 months (range: 13–41 months) and, overall, 47% of the respondents (n = 1543) reported pain and 58% reported sensory disturbances (n = 1882). Factors associated with chronic pain included young age, adjuvant radiotherapy and axillary lymph node dissection, but not chemotherapy or type of surgery. The likelihood of increased sensory disturbances was associated with young age and axillary lymph node dissection but not with adjuvant therapy or type of surgery.

Recently, Gärtner et al. reported findings from a national cross-sectional study on chronic pain and sensory disturbances after breast cancer surgery [1]. In general, pain in breast cancer patients, either acute or chronic, remains unresolved. The exact mechanism of the development of pain is not known, but it is probably a neuropathic condition that results from damage to the nerves in the axilla and/or the chest wall during surgery [2]. Other causes of chronic pain after breast cancer surgery include type of breast cancer surgery, axillary procedures, adjuvant chemotherapy and radiation therapy [3]. Additional risk factors include young age, preoperative breast pain and acute postoperative pain intensity [4,5]. One study found that higher intensities of postoperative acute pain were associated with chronic pain development and higher long-term analgesic consumption [6]. In addition, psychological factors, such as preoperative anxiety, were found to make independent contributions to the development of acute pain following breast cancer surgery that, in turn, might lead to chronic pain. Katz et al. demonstrated that greater preoperative anxiety was associated with clinically meaningful acute pain that persisted after surgery [7].

Breast cancer patients might develop pain in several forms and in different areas of their body. One study assessed three distinct categories of postmastectomy pain: phantom breast pain, scar pain and other mastectomy-related pain. The results demonstrated that each of these three types of pain were strongly related to one another, but, collectively, the presence of ‘other mastectomy-related pain’ was a stronger unique predictor of disability and distress compared with the other two categories of pain [8].

However, studying postsurgical chronic pain in breast cancer patients remains an unresolved topic. This priority paper evaluation attempts to highlight the findings from one of the most recent publications on the subject.

Findings

In a nationwide cross-sectional study published in the Journal of the American Medical Association, Gärtner et al. examined the prevalence, location and severity of persistent pain and sensory disturbances among women following breast cancer surgery [1]. A detailed questionnaire was designed to collect data in order to address four specific regions of pain symptoms: the breast area, the axilla, the arm and the side of the body. In total, 3253 out of 3754 eligible women (87%) participated in the study.

Pain

Overall, 1543 patients (47%) reported pain. Of these, 201 (13%) had severe pain, 595 (39%) had moderate pain and 733 (48%) had light pain, as rated by patients on a ten-point numeric scale, where 0 indicated no pain and 10 indicated the worst imaginable pain. A total of 278 patients (18%) reported pain in only one area, 435 (28%) in two areas, 429 (28%) in three areas and 400 (26%) in all four areas. As expected, the most frequently reported area of pain was the breast area, (n = 1331; 86%), followed by the axilla (n = 975; 63%), the arm (n = 872; 57%) and, lastly, the side of the body (n = 857; 56%). A total of306 patients (20% of those who reported pain) had contacted a physician within the 3 months prior to surgery owing to pain, 439 (28%) had taken painkillers and 397 (26%) had received other treatments for pain.

Performing multiple logistic regression analysis adjusted for age, type of surgery (mastectomy vs breast conservation), axillary procedures (axillary lymph node dissection vs sentinel lymph node dissection) and adjuvant therapy (chemotherapy or radiotherapy), the authors of the study found that chronic pain was associated with young age (breast conservation [in patients aged 18–39 years], odds ratio [OR]: 3.62; 95% CI: 2.25–5.82; p < 0.001; mastectomy [in patients aged 40–49 years], OR: 1.72; 95% CI: 1.21–2.45; p = 0.03), adjuvant radiotherapy (OR: 1.50; 95% CI: 1.08-2.07; p = 0.03) and axillary lymph node dissection (OR: 1.77; 95% CI: 2.87-8.69; p < 0.001), but not chemotherapy (OR: 1.01; 95% CI: 0.85-1.21; p = 0.91) or type of surgery (mastectomy compared with breast conservation, OR: 1.13; 95% CI: 0.84-1.53; p = 0.41).

Sensory disturbances

In total, 1882 breast cancer patients (58%) reported sensory disturbances or discomfort. The most frequently reported areas were the axilla (n = 1239; 66%), followed by the arm (n = 986; 52%), the breast area (n = 816; 43%) and, lastly, the side of the body (n = 573; 30%).

Similarly, performing multiple logistic regression analysis adjusted for age, type of surgery (mastectomy vs breast conservation), axillary procedures (axillary lymph node dissection vs sentinel lymph node dissection) and adjuvant therapy (chemotherapy or radiotherapy), the researchers found that the likelihood of increased sensory disturbances was associated with young age (breast conservation [in patients aged 18–39 years], OR: 5.00; 95% CI: 2.87-8.69; p < 0.001; mastectomy [in patients aged 18–39 years], OR: 6.06; 95% CI: 2.07-17.7; p = 0.03) and axillary lymph node dissection (OR: 4.97; 95% CI: 3.92-6.30; p < 0.001), but not adjuvant therapy or type of surgery.

Comment

The study by Gärtner et al. is the largest study to date that has reported on chronic pain after breast cancer surgery and that allowed for adequate statistical analysis in 12 different patient groups and indicated correlates and determinants. The findings were similar to the earlier well-designed studies on the topic, where it has been demonstrated that chronic pain and sensory disturbances after breast cancer surgery occurred in approximately 50% of patients. Interestingly, a study of 1316 breast cancer patients from the same country – Denmark – using a similar database and reporting on chronic pain and other sequelae in long-term breast cancer survivors (5-years postsurgery) found that the prevalence of chronic pain was 42% and paresthesias occurred in 47% of patients. The study indicated that, in total, 29% of patients reported having chronic pain related to breast cancer. The findings also reported that other sequelae related to breast cancer were arm/shoulder swelling (25%), phantom sensation (19%) and allodynia (15%) [9].

However, the study by Gärtner et al., although a large study, has several limitations, including the cross-sectional design and a homogenous study population (white and well-educated Danish women). There is evidence that nonwhite woman with breast cancer experience greater postoperative pain compared with white patients [10]. In addition, it would have been beneficial if the authors had assessed postsurgical acute pain, including psychosocial factors, in their analyses [1].

The prevalence of chronic pain in breast cancer patients varies from 10 to 20% up to almost 60–70%. The variation in findings on the prevalence of pain is attributed to several factors: selection of patients, instruments used to measure pain, assessment methods, pain area and follow-up period. Nonetheless, the evidence suggests that breast cancer patients experience chronic pain even several years postsurgery. One study reported that arm lymphedema (13%), pain (36%) and sensation of heaviness (21%) in the upper limbs can be present 5 years after surgery [11]. This implies that a guideline is needed in order to regulate how and when to measure pain in breast cancer patients so that the results can be compared and appropriate interventions can be implemented. A recent proposal for pain quantification and localization in a group of breast cancer patients might be a solution [12].

Conclusion & future perspective

In general, pain has a significant effect on quality of life in breast cancer patients [11,13]. Pain might also cause psychological distress in breast cancer patients [14]. Furthermore, pain might even predict the survival duration in breast cancer patients [15]. In addition, pain is associated with other disturbing symptoms, such as fatigue, in patients with breast cancer [16]. Thus, as suggested, pain demands careful attention and a search for achieving effective relief after breast cancer surgery [17]. Indeed, tailored pain management for every breast cancer patient's care is essential. Perhaps moving from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk [18] might help to overcome chronic neuropathic pain in breast cancer patients who receive surgery.

Executive summary

• Chronic pain and sensory disturbances affect approximately 50% of patients even several years after breast cancer surgery.

• A nationwide cross-sectional study from Demark indicated that young age, adjuvant radiotherapy and axillary lymph node dissection were significant predictors of chronic pain 2–3 years after breast cancer surgery.

• The same study indicated that young age and axillary lymph node dissection were significant predictors of sensory disturbances 2–3 years after breast cancer surgery.

• An agreed guideline for pain medicine in breast cancer patients (including how and when to measure pain) and its management is essential.

• The contribution of type of surgery was not significant for both increased chronic pain and sensory disturbances; however, axillary procedure was significant.