Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis

Laurence Leysen & David Beckwée & Jo Nijs, & Roselien P & Thomas Bilterys & Sofie Vermeir & Nele Adriaenssens. Support Care Cancer (2017) 25:3607–3643

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Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis

Laurence Leysen & David Beckwée & Jo Nijs, & Roselien P & Thomas Bilterys & Sofie Vermeir & Nele Adriaenssens. Support Care Cancer (2017) 25:3607–3643.

Background

Breast cancer remains the number 1 lethal malignancy in women. With rising incidence and decreased mortality, the number of breast cancer survivors has increased. Consequently, sequelae, such as pain, are becoming more important. Purpose The purpose of this study was to identify risk factors for the development of pain in breast cancer survivors.

Methods

PubMed and Web of Science were systematically screened for studies encompassing risk factors for the development of pain in breast cancer survivors. Meta-analyses were carried out for risk factors described in more than one article. Moderator analysis was performed in case of high heterogeneity (I2 > 50%) across studies.

Results

Seventeen studies were found eligible. Meta-analyses were performed for 17 factors. Significant differences for the odds of developing chronic pain were found for BMI (overall OR: 1.34, 95%CI 1.08–1.67, p = 0.008), education (overall OR:1.23,95%CI1.07–1.42,p=0.005),lymphedema(overall OR: 2.58, 95%CI 1.93–3.46, p < 0.00001), smoking status (overall OR: 0.75, 95%CI 0.62–0.92, p = 0.005), axillary lymph node dissection (overall OR: 1.25, 95%CI 1.04–1.52, p=0.02),chemotherapy(overallOR:1.44,95%CI1.24–1.68, p < 0.00001), and radiotherapy (overall OR: 1.32, 95%CI 1.17–1.48, p < 0.00001). After performing moderator analyses for age, comorbidities, hormone therapy, and breast surgery, hormone therapy became a significant risk factor as well (overall OR: 1.33, 95%CI 1.15–1.54, p = 0.0001).

Conclusion

BMI > 30, education < 12–13 years, lymphedema, not smoking, axillary lymph node dissection, chemotherapy, hormone therapy, and radiotherapy were significantly associated with higher odds for the development of chronic pain, with lymphedema being the biggest risk factor. Lack of uniformity across the studies in defining pain, follow-up, measurement tools, and cut-off values for the diagnosis of pain was noted, resulting in greater inter-study variability

Main findings

  • Seven out of the 17 examined factors (BMI > 30, education <12–13 years, lymphedema, no- or ex-smoker, axillary lymph node dissection, chemotherapy, and radiotherapy) demonstrated to be significantly associated with an elevated chance for the development of chronic pain in breast cancer survivors, with lymphedema being the strongest risk factor.
  • Hormone therapy became a significant risk factor for the development of chronic pain in breast cancer survivors.
  • Jeong et al.stated that the rotator cuff tendinitis is a frequently seen complication in patients with lymphedema. A total of 53.3% of the patients with lymphedema were diagnosed with a supraspinatus tear (75% showed a partial thickness tear and 25% a full thickness tear), 53.3% with an adhesive capsulitis, 13.3% with a tenosynovitis, 13.3% with an acromioclavicular arthritis, and 13.3% with a subdeltoid bursitis. All these definitive structural abnormalities in patients with lymphedema might in turn lead to the development of pain.
  • Obesity could possibly lead to the development of pain due to mechanical stress and metabolic disruption.
  • The presence of both pain and obesity often lead to a vicious cycle of pain–inactivity–obesity.
  • AWS can trigger a painful sensation with abduction of the shoulder.
  • Chemotherapy can cause damage to the nerves and induce peripheral neuropathy; however, the exact pathophysiologic mechanism underlying the nerve injury in chemotherapy-induced peripheral neuropathy (CIPN) is still not completely understood.