title: Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies.
abstract: BACKGROUND
  Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer.
  
  
  METHODS
  We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase.
  
  
  RESULTS
  Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy.
  
  
  CONCLUSIONS
  Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery.
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Kennedy
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Romerosa
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Henry Y
authors.initials: HY
authors.lastname: Kwon
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Alka
authors.initials: A
authors.lastname: Kaushal
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Samantha
authors.initials: S
authors.lastname: Craigie
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Carlos P B
authors.initials: CPB
authors.lastname: de Almeida
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Couban
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Parascandalo
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Zain
authors.initials: Z
authors.lastname: Izhar
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Reid
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: James S
authors.initials: JS
authors.lastname: Khan
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: McGillion
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland bussejw@mcmaster.ca.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Busse
mesh_terms: D000367:Age Factors; D001365:Axilla; D001943:Breast Neoplasms / Q000601:surgery*; D017024:Chemotherapy, Adjuvant / Q000706:statistics & numerical data*; D059350:Chronic Pain / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008197:Lymph Node Excision / Q000706:statistics & numerical data*; D008408:Mastectomy / Q000706:statistics & numerical data; D015412:Mastectomy, Segmental / Q000706:statistics & numerical data*; D059373:Mastodynia / Q000453:epidemiology*; D064887:Observational Studies as Topic; D016017:Odds Ratio; D010147:Pain Measurement; D010149:Postoperative Pain / Q000453:epidemiology; D057234:Preoperative Period; D018714:Radiotherapy, Adjuvant / Q000706:statistics & numerical data*; D012307:Risk Factors