Abstract
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 (I 2 > 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%CI 1.07–1.42, 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 (overall OR: 1.44, 95%CI 1.24–1.68, 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.
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References
Ferlay J et al (2015) Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386
Ferlay J et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917
Katanoda K, Matsuda T (2014) Five-year relative survival rate of breast cancer in the USA, Europe and Japan. Jpn J Clin Oncol 44(6):611
Organization, W.H., World cancer report 2014. 2014, Lyonn, France: International Agency for Research on Cancer.
Befort CA, Klemp J (2011) Sequelae of breast cancer and the influence of menopausal status at diagnosis among rural breast cancer survivors. J Women's Health 20(9):1307–1313
Glare PA et al (2014) Pain in cancer survivors. J Clin Oncol 32(16):1739–1747
Forsythe LP et al (2013) Pain in long-term breast cancer survivors: The role of body mass index, physical activity, and sedentary behavior. Breast Cancer Res Treat 137(2):617–630
Pain, I.A.f.t.S.o. Pain, IASP Taxonomy. 2014 2014–10-06 [cited 2016 2016–03-26]; Available from: http://www.iasp-pain.org/Taxonomy - Pain.
Merskey, H. and N. Bogduk, Eds. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. Second edition ed. 1994, IASP Press: Seattle
Chang SH, Metha V, Langford R (2009) Acute and chronic pain following breast surgery. Acute Pain 11(1):1–14
Andersen KG, Kehlet H (2011) Persistent pain after breast cancer treatment: A critical review of risk factors and strategies for prevention. J Pain 12(7):725–746
Liberati A et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. J Clin Epidemiol 62(10):e1–34
NCI, O.o.C.S., About Cancer Survivorship Research: Survivorship Definitions.. 2012, Washington, DC
Elmagarmid, A., et al., Rayyan: a systematic reviews web app for exploring and filtering searches for eligible studies for Cochrane Reviews., in Evidence-Informed Public Health: Opportunities and Challenges. Abstracts of the 22nd Cochrane Colloquium. 2014, John Wiley & sons: Hyderabad, India
Bredal IS et al (2014) Chronic pain in breast cancer survivors: Comparison of psychosocial, surgical, and medical characteristics between survivors with and without pain. J Pain Symptom Manag 48(5):852–862
Moloney N et al (2016) Prevalence and risk factors associated with pain 21 months following surgery for breast cancer. Support Care Cancer 24(11):4533–4539
Steyaert A et al (2016) Does the perioperative analgesic/anesthetic regimen influence the prevalence of long-term chronic pain after mastectomy? J Clin Anesth 33:20–25
von Elm E et al (2014) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg (London, England) 12(12):1495–1499
Higgins JP et al (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560
Higgins, J.P.T. and S. Green, Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.1 [updated September 2008]. Chapter 9: Analysing data and undertaking meta-analyses., ed. J.J. Deeks, J.P.T. Higgins, and D.G. Altman. 2008: The Cochrane Collaboration.
Johannsen M et al (2015) Socio-demographic, treatment-related, and health behavioral predictors of persistent pain 15 months and 7-9 years after surgery: A nationwide prospective study of women treated for primary breast cancer. Breast Cancer Res Treat 152(3):645–658
Peuckmann V et al (2009) Chronic pain and other sequelae in long-term breast cancer survivors: Nationwide survey in Denmark. Eur J Pain 13(5):478–485
Romero A et al (2016) Prevalence of persistent pain after breast cancer treatment by detection mode among participants in population-based screening programs. BMC Cancer 16
Andersen Juhl A, Christiansen P, Damsgaard TE (2016) Persistent pain after breast cancer treatment: A questionnaire-based study on the prevalence, associated treatment variables, and pain type. J Breast Cancer 19(4):447–454
Alkan A et al (2016) Breast cancer survivors suffer from persistent postmastectomy pain syndrome and posttraumatic stress disorder (ORTHUS study): A study of the palliative care working committee of the Turkish oncology group (TOG). Support Care Cancer 24(9):3747–3755
Lundstedt D et al (2015) Radiation therapy to the plexus brachialis in breast cancer patients: Analysis of paresthesia in relation to dose and volume. Int J Radiat Oncol Biol Phys 92(2):277–283
Bantema-Joppe EJ et al (2012) Simultaneous integrated boost irradiation after breast-conserving surgery: Physician-rated toxicity and cosmetic outcome at 30 months' follow-up. Int J Radiat Oncol Biol Phys 83(4):e471–e477
Bell RJ et al (2014) Persistent breast pain 5 years after treatment of invasive breast cancer is largely unexplained by factors associated with treatment. J Cancer Surviv 8(1):1–8
Gulluoglu BM et al (2006) Factors related to post-treatment chronic pain in breast cancer survivors: The interference of pain with life functions. Int J Fertil Womens Med 51(2):75–82
Calhoun C, Helzlsouer KJ, Gallicchio L (2015) Racial differences in depressive symptoms and self-rated health among breast cancer survivors on aromatase inhibitor therapy. J Psychosoc Oncol 33(3):263–277
Crandall C et al (2004) Association of breast cancer and its therapy with menopause-related symptoms. Menopause- J North Am Menopause Soc 11(5):519–530
van Londen GJ et al (2014) Associations between adjuvant endocrine therapy and onset of physical and emotional concerns among breast cancer survivors. Support Care Cancer 22(4):937–945
Lundstedt D et al (2010) Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial. Radiother Oncol 97(2):281–287
Crandall C et al (2004) Association of breast cancer and its therapy with menopause-related symptoms. Menopause 11(5):519–530
Bell RJ et al (2014) Persistent breast pain 5 years after treatment of invasive breast cancer is largely unexplained by factors associated with treatment. Journal of Cancer Survivorship 8(1):1–8
Berrios-Rivera R, Rivero-Vergine A, Romero I (2008) The pediatric cancer hospitalization experience: Reality co-constructed. J Pediatr Oncol Nurs 25(6):340–353
Kim SJ, Park YD (2008) Effects of complex decongestive physiotherapy on the oedema and the quality of life of lower unilateral lymphoedema following treatment for gynecological cancer. Eur J Cancer Care (Engl) 17(5):463–468
Jeong HJ et al (2011) Causes of shoulder pain in women with breast cancer-related lymphedema: A pilot study. Yonsei Med J 52(4):661–667
Taylor RJ et al (2014) Pain and obesity in the older adult. Curr Pharm Des 20(38):6037–6041
Okifuji A, Hare BD (2015) The association between chronic pain and obesity. J Pain Res 14(8):399–408
Piper, M., et al (2016), Axillary Web Syndrome: Current Understanding and New Directions for Treatment. Ann Plast Surg
Yeung WM, McPhail SM, Kuys SS (2015) A systematic review of axillary web syndrome (AWS). J Cancer Surviv 9(4):576–598
Cregg R, Anwar S, Farquhar-Smith P (2013) Persistent postsurgical pain. Curr Opin Support Palliat Care 7(2):144–152
Shipton EA (2011) The transition from acute to chronic post surgical pain. Anaesth Intensive Care 39(5):824–836
Delanian S, Lefaix JL, Pradat PF (2012) Radiation-induced neuropathy in cancer survivors. Radiother Oncol 105(3):273–282
Grisold W, Cavaletti G, Windebank AJ (2012) Peripheral neuropathies from chemotherapeutics and targeted agents: Diagnosis, treatment, and prevention. Neuro-Oncology 14:45–54
Bhagra A, Rao RD (2007) Chemotherapy-induced neuropathy. Curr Oncol Rep 9(4):290–299
Boland EG et al (2014) Central pain processing in chronic chemotherapy-induced peripheral neuropathy: A functional magnetic resonance imaging study. PLoS One 9(5):e96474
Lee E et al (2016) Characterization of risk factors for adjuvant radiotherapy-associated pain in a tri-racial/ethnic breast cancer population. Pain 157(5):1122–1131
Burton AW et al (2007) Chronic pain in the cancer survivor: A new frontier. Pain Med 8(2):189–198
Levy MH, Chwistek M, Mehta RS (2008) Management of chronic pain in cancer survivors. Cancer J 14(6):401–9
Altundag K, Ibrahim NK (2006) Aromatase inhibitors in breast cancer: An overview. Oncologist 11(6):553–562
Mao JJ et al (2009) Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors. Cancer 115(16):3631–3639
Beckwee, D., et al. (2017) Prevalence of aromatase inhibitor-induced arthralgia in breast cancer: A systematic review and meta-analysis. Support Care Cancer
Howell A et al (2005) Results of the ATAC (Arimidex, tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 365(9453):60–62
Goss PE et al (2003) A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349(19):1793–1802
Jakesz R et al (2005) Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: Combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 366(9484):455–462
Burstein HJ (2007) Aromatase inhibitor-associated arthralgia syndrome. Breast 16(3):223–234
Peppone LJ et al (2015) The effect of YOCAS(c)((R)) yoga for musculoskeletal symptoms among breast cancer survivors on hormonal therapy. Breast Cancer Res Treat 150(3):597–604
Hershman DL, Loprinzi C, Schneider BP (2015) Symptoms: Aromatase inhibitor induced Arthralgias. Adv Exp Med Biol 862:89–100
Fusi C et al (2014) Steroidal and non-steroidal third-generation aromatase inhibitors induce pain-like symptoms via TRPA1. Nat Commun 5:5736
Turk DC, Wilson HD (2010) Fear of pain as a prognostic factor in chronic pain: Conceptual models, assessment, and treatment implications. Curr Pain Headache Rep 14(2):88–95
Boersma K, Linton SJ (2005) Screening to identify patients at risk: Profiles of psychological risk factors for early intervention. Clin J Pain 21(1):38–43
Rashiq S, Dick BD (2014) Post-surgical pain syndromes: A review for the non-pain specialist. Can J Anesth 61(2):123–130
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Jo Nijs is holder of a Chair funded by the Berekuyl Academy, the Netherlands. Roselien Pas is a PhD student funded by the Berekuyl Acadely Chair.
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The authors declare that they have no conflict of interest.
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Leysen, L., Beckwée, D., Nijs, J. et al. Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis. Support Care Cancer 25, 3607–3643 (2017). https://doi.org/10.1007/s00520-017-3824-3
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DOI: https://doi.org/10.1007/s00520-017-3824-3