Nearly 25 percent of patients who undergo breast cancer surgery experience pain categorized as significant and persistent, and women with preoperative breast pain are at highest risk for having pain postsurgically as well. That was the conclusion of a study reported in the Journal of Pain (2012;13:1172-1187) led by a long-time researcher in this area, Christine Miaskowski, RN, PhD, FAAN, Professor and Associate Dean for Academic Affairs of the Department of Physiological Nursing at the University of California, San Francisco.
“I think the whole notion of making clinicians aware that this is a problem is useful,” she said in an interview. “I talk to many surgeons, including breast surgeons, who don't believe that this is a clinical problem.”
While a growing body of evidence suggests that postoperative pain is fairly common, individuals still shouldn't have to experience the symptom, she added. The most easily modifiable risk factor at this point is immediate postoperative pain.
Asked for his opinion, Charles S. Cleeland, PhD, the McCullough Professor of Cancer Research and Department Chair of the Department of Symptom Research at the University of Texas MD Anderson Cancer Center, agreed: “This research is consistent with many other studies showing that a significant portion of women with breast cancer experience pain after treatment. The clinical implication is that we need to include symptom assessment and pain assessment in all visits with patients,” he said.
The study is also the first to identify distinct subgroups of women with persistent breast pain following breast cancer surgery.
Defining risk groups for developing persistent pain is extremely important, noted Tanya M. Nikolova, MD, Assistant Attending Physician in the Pain and Palliative Care Service at Memorial Sloan-Kettering Cancer Center (MSKCC). “Identifying vulnerable individuals will help physicians counsel patients preemptively, offering them solutions for reducing the risk of developing persistent pain,” she said.
Overall, the study was well done and gives physicians data upon which to build further investigation, commented Richard J. Bleicher, MD, Attending Surgeon and Director of the Breast Fellowship Program and Associate Professor of Surgical Oncology at Fox Chase Cancer Center. Still, he added, although the information can reassure women that chronic pain after breast cancer surgery is a normal phenomenon, it is too early for the study to have specific implications in clinical practice.
Miaskowski and her colleagues evaluated the questionnaire responses of 398 women who underwent breast cancer surgery as part of a larger study on neuropathic pain and lymphedema. Patients were treated at breast care facilities in a comprehensive cancer center, two public hospitals, and four community practices and were monitored monthly for six months.
In addition to using a variety of questionnaires to evaluate subjective measures, the researchers also used a type of modeling called growth mixture to detect underlying changes in symptom severity over time and to identify patient subgroups. The researchers then assessed women within these subgroups for differences in demographic, preoperative, intraoperative, and perioperative characteristics.
About 32 percent of the patients reported having no breast pain, 43 percent had mild pain, 13 percent had moderate pain, and almost 12 percent reported severe pain that persisted for six months. Younger age, less education, non-white ethnicity, and lower income were demographic characteristics associated with the severe pain group.
The authors noted that although the findings on non-white ethnicity support prior research (Pain Med 2009;10:708-715), these patients were also more likely to present with advanced disease and to require an axillary lymph node dissection (ALND), both of which may contribute to severe pain.
Additionally, women with severe pain who have lower socioeconomic status may be medically underserved, and often these individuals don't have access to physical therapy, analgesics, and other approaches that could help to reduce pain, Cleeland noted.
The researchers also found that patients in the severe pain group had high preoperative breast pain scores. “We were really surprised that 25 percent of women going into surgery have pain in their breast,” Miaskowski said. The severe pain group also experienced more changes in breast sensations, less preoperative mobility in the affected arm, a greater severity of postoperative pain, had more lymph nodes removed, and were more likely to undergo an auxiliary lymph node dissection.
Moreover, patients in the severe pain class were more likely to be re-excised or to need a mastectomy following the original surgery. The likelihood of having undergone radiation therapy was higher in the moderate pain class than in the mild and severe classes, the researchers reported.
Women in the moderate and severe pain groups were also more likely than the other groups to report preoperative depression, anxiety, sleep disturbance, and fatigue. Those in the mild, moderate, and severe pain groups reported poorer preoperative quality of life, and worse social and psychological well being than those in the no pain group.
Miaskowski noted that patients in the severe pain group were generally not receiving analgesics for pain, and overall, pain subgroups were not associated with use of analgesics.
The study limitations were minor, including the relatively small number of patients in each pain class—“but this is a challenge in conducting pain research in general,” Nikolova noted. The research also did not include data on arm pain and separate data from different health care settings. For example, she said, outcomes might have been different in community practices compared with designated breast centers.
Additionally, about 20 percent of women didn't complete the study, and data on pain severity within the first 48 hours of surgery was collected at one month, so there may have been recall bias due to that time lag. In addition, Cleeland noted, although it wasn't the investigators' fault, some of the operative details weren't as rich as they needed to be to assess why these individuals were experiencing pain.
Identifying subgroups of patients who are at higher risk of having moderate to severe postoperative pain, especially before surgery, can help oncologists ensure that selected patients benefit from meeting with anesthesiologists, pain clinic staff, or physical therapists, noted Mehra Golshan, MD, Director of Breast Surgical Services at Dana-Farber/Brigham and Women's Cancer Center and the Al Tuwaijri Chair of Surgical Oncology and Associate Professor of Surgery at Harvard Medical School. These patients can then be closely followed peri- and postoperatively.
The symptom of pain is definitely under-assessed, Cleeland said. The initial evaluation ranking pain may be conducted by office staff and then not viewed by practitioners, he noted, adding that entering the information into an electronic medical record and tracking pain over time could help to address this problem.
Also, as has been noted historically for cancer-related pain in general, patients may underreport pain because they fear it is a sign of disease recurrence or progression.
To address pain, practitioners should tailor an analgesic program to the 25 percent of women experiencing chronic moderate to severe pain, Cleeland said. Some patients don't want to take pain medication due to potential side effects or an overall fear of taking painkillers. However, drug titration can help to avoid such issues.
Nikolova also noted that several studies have tested different agents providing so-called “preventive” analgesia, delivered in the perioperative period, and some agents—for example, venlafaxine—have shown promising results in potentially lowering persistent pain (Clin J Pain 2010;26:381-385).
Nonpharmacological approaches are also possible, she continued, explaining that the MSKCC Pain and Palliative Care Service works closely with Rehabilitation Medicine, Anesthesia Pain, and Integrative Medicine staff there to offer patients such options as nerve blocks, botulinum toxin for muscle spasm, transcutaneous electrical nerve stimulation, acupuncture, yoga, and body/mind techniques.
In addition to screening for pain, all providers should be assessing patients for poor preoperative functional status, depression, anxiety, and sleep disturbance, and patients may benefit from pharmacotherapy or referral to a psychologist, psychiatrist, occupational therapist, or rehabilitation medicine specialist, she said.
Nikolova suggested that further research evaluate genetic polymorphism, especially regarding the risk of persistent pain and response to analgesics. Gene therapies, preventive analgesia and development of perioperative pain management programs will also need to be further explored and implemented.
“We need to understand inter-individual variability, clinical and demographic characteristics, and whether we can differentiate among pain groups based on genetic factors and molecular markers,” noted Miaskowski, who said she is currently working on research that shows that molecular markers in breast cancer patients who have no pain are different from those who have severe pain, even within inflammatory pathways. This type of research should help to identify who is at great risk for more severe pain, she said.
Miaskowski said she is also starting to analyze data six months postsurgery and will look at the effect of certain medications—for example, aromatase inhibitors.
A better understanding of the correlation between postoperative pain and anxiety and depression is also needed, Bleicher said. “This falls along the neurologic realm. Maybe these patients have some slight neurologic differences. If we modulate some of these other neurologic symptoms, will that help bring down patients' pain scores postoperatively? Is this a global neurological phenomenon?”
Studying larger groups of patients across the country at various clinics, as well as patients from a variety of ethnic groups would also be beneficial, Golshan said. “However, this is the first study of this size that has looked at as many factors as possible. It opens up the need for more studies and funding of pain research.”