Skip to main content

Gait, balance, and patient-reported outcomes during taxane-based chemotherapy in early-stage breast cancer patients

Breast Cancer Research and Treatment volume 164, pages 69–77 (2017)Cite this article

Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of several commonly used chemotherapy drugs including taxanes, vinca alkaloids, and platinum compounds. Development of CIPN is highly variable, both in self-reported symptoms and functional consequences, and can be severe enough to alter dose intensity.

Purpose

To describe the natural histories of both patient-reported symptoms of CIPN and functional impairments in breast cancer patients undergoing taxane-based chemotherapy.

Methods

Thirty-three breast cancer patients (32 female/1 male; 47.8 ± 11.2 years; n = 17 stage II/n = 16 stage III) were enrolled. Patients completed self-reports of symptoms and function (e.g., EORTC QLQ-CIPN20) and objective measures of physical function (i.e., balance and gait testing) in an outpatient oncology clinic at five timepoints: (1) baseline—prior to starting chemotherapy, (2–4) before starting subsequent chemotherapy cycles, and (5) 1–3 months after receiving their last taxane infusion.

Results

Significant negative changes in both patient-reported outcomes and objective functional measures were observed. Decreased balance was observed after the first chemotherapy cycle (28% increase in medial–lateral excursion of the center of pressure, p = 0.016) and progressed with cumulative exposure (43% increase, p < 0.001). Patients also demonstrated slower walking speeds (5% decrease, p = 0.003) as they progressed through treatment. These functional deficits were mirrored with increased patient-reported symptom severity for all EORTC QLQ-CIPN20 subscales (all p < 0.05).

Conclusion

This study longitudinally assessed patient-reported outcomes concurrently with balance and gait testing in patients undergoing taxane therapy. Taxane treatment was associated with the development of clinically relevant problems in both CIPN symptoms and patient function.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Tofthagen C, Overcash J, Kip K (2012) Falls in persons with chemotherapy-induced peripheral neuropathy. Support Care Cancer 20:583–589

    Article  PubMed  Google Scholar 

  2. Tinetti ME (2003) Preventing falls in elderly persons. N Engl J Med 348(1):42–49. doi:10.1056/NEJMcp020719

    Article  PubMed  Google Scholar 

  3. Balducci S, Iacobellis G, Parisi L, Di Biase N, Calandriello E, Leonetti F, Fallucca F (2006) Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complicat 20(4):216–223. doi:10.1016/j.jdiacomp.2005.07.005

    Article  PubMed  Google Scholar 

  4. Bakitas MA (2007) Background noise: the experience of chemotherapy-induced peripheral neuropathy. Nurs Res 56(5):323–331. doi:10.1097/01.NNR.0000289503.22414.79

    Article  PubMed  Google Scholar 

  5. Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 155:2461–2470

    Article  PubMed  Google Scholar 

  6. Ocean AJ, Vahdat LT (2004) Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. Support Care Cancer 12(9):619–625. doi:10.1007/s00520-004-0657-7

    PubMed  Google Scholar 

  7. Rubenstein LZ, Josephson KR (2002) The epidemiology of falls and syncope. Clin Geriatr Med 18(2):141–158

    Article  PubMed  Google Scholar 

  8. Kolb NA, Smith AG, Singleton JR, Beck SL, Stoddard GJ, Brown S, Mooney K (2016) The association of chemotherapy-induced peripheral neuropathy symptoms and the risk of falling. JAMA Neurol 73(7):860–866. doi:10.1001/jamaneurol.2016.0383

    Article  PubMed  Google Scholar 

  9. Macgilchrist C, Paul L, Ellis B, Howe TE, Kennon B, Godwin J (2010) Lower-limb risk factors for falls in people with diabetes mellitus. Diabet Med 27(2):162–168

    Article  CAS  PubMed  Google Scholar 

  10. Bao T, Basal C, Seluzicki C, Li SQ, Seidman AD, Mao JJ (2016) Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk. Breast Cancer Res Treat 159(2):327–333. doi:10.1007/s10549-016-3939-0

    Article  CAS  PubMed  Google Scholar 

  11. Miaskowski C, Mastick J, Paul SM, Topp K, Smoot B, Abrams G, Chen LM, Kober KM, Conley YP, Chesney M, Bolla K, Mausisa G, Mazor M, Wong M, Schumacher M, Levine JD (2017) Chemotherapy-induced neuropathy in cancer survivors. J Pain Symptom Manag. doi:10.1016/j.jpainsymman.2016.12.342

    Google Scholar 

  12. Gewandter J, Fan L, Magnuson A, Mustian K, Peppone L, Heckler C, Hopkins J, Tejani M, Morrow G, Mohile S (2013) Falls and functional impairments in cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study. Support Care Cancer 21(7):2059–2066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wampler MA, Topp KS, Maiskowski C, Byl NN, Rugo HS, Hamel K (2007) Quantitative and clinical description of postural instability in women with breast cancer treated with taxane chemotherapy. Arch Phys Med Rehabil 88:1002–1008

    Article  PubMed  Google Scholar 

  14. Kneis S, Wehrle A, Freyler K, Lehmann K, Rudolphi B, Hildenbrand B, Bartsch HH, Bertz H, Gollhofer A, Ritzmann R (2016) Balance impairments and neuromuscular changes in breast cancer patients with chemotherapy-induced peripheral neuropathy. Clin Neurophysiol 127(2):1481–1490. doi:10.1016/j.clinph.2015.07.022

    Article  PubMed  Google Scholar 

  15. Streckmann F, Kneis S, Leifert JA, Baumann FT, Kleber M, Ihorst G, Herich L, Grüssinger V, Gollhofer A, Bertz H (2014) Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy. Ann Oncol 25:493–499

    Article  CAS  PubMed  Google Scholar 

  16. Schwenk M, Garland LL, Grewal GS, Holloway D, Muchna A, Mohler J, Najafi B (2015) Wearable sensor-based balance training in older adult cancer patients with chemotherapy-induced neuropathy: a randomized controlled trial. In: ASCO annual meeting proceedings

  17. Winters-Stone KM, Torgrimson B, Horak F, Eisner A, Nail L, Leo MC, Chui S, Luoh SW (2011) Identifying factors associated with falls in postmenopausal breast cancer survivors: a multi-disciplinary approach. Arch Phys Med Rehabil 92(4):646–652. doi:10.1016/j.apmr.2010.10.039

    Article  PubMed  PubMed Central  Google Scholar 

  18. Niederer D, Schmidt K, Vogt L, Egen J, Klingler J, Hubscher M, Thiel C, Bernhorster M, Banzer W (2014) Functional capacity and fear of falling in cancer patients undergoing chemotherapy. Gait Posture 39(3):865–869. doi:10.1016/j.gaitpost.2013.11.014

    Article  PubMed  Google Scholar 

  19. Winters-Stone KM, Hilton C, Luoh S-W, Jacobs P, Faithfull S, Horak FB (2016) Comparison of physical function and falls among women with persistent symptoms of chemotherapy-induced peripheral neuropathy. In: ASCO annual meeting proceedings

  20. Loprinzi CL, Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, Le-Lindqwister NA, Soori GS, Jaslowski AJ, Novotny PJ, Lachance DH (2011) Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol 29(11):1472–1478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Monfort SM, Pan X, Patrick R, Singaravelu J, Loprinzi CL, Lustberg MB, Chaudhari AM (2016) Natural history of postural instability in breast cancer patients treated with taxane-based chemotherapy: a pilot study. Gait Posture 48:237–242. doi:10.1016/j.gaitpost.2016.06.011

    Article  PubMed  Google Scholar 

  22. Maki BE, Holliday PJ, Topper AK (1994) A prospective study of postural balance and risk of falling in an ambulatory and independent elderly population. J Gerontol 49(2):M72–84

    Article  CAS  PubMed  Google Scholar 

  23. Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, Brach J, Chandler J, Cawthon P, Connor EB, Nevitt M, Visser M, Kritchevsky S, Badinelli S, Harris T, Newman AB, Cauley J, Ferrucci L, Guralnik J (2011) Gait speed and survival in older adults. JAMA 305(1):50–58. doi:10.1001/jama.2010.1923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Perera S, Mody SH, Woodman RC, Studenski SA (2006) Meaningful change and responsiveness in common physical performance measures in older adults. J Am Geriatr Soc 54(5):743–749. doi:10.1111/j.1532-5415.2006.00701.x

    Article  PubMed  Google Scholar 

  25. MacAulay RK, Allaire TD, Brouillette RM, Foil HC, Bruce-Keller AJ, Han H, Johnson WD, Keller JN (2015) Longitudinal assessment of neuropsychological and temporal/spatial gait characteristics of elderly fallers: taking it all in stride. Front Aging Neurosci 7:34. doi:10.3389/fnagi.2015.00034

    Article  PubMed  PubMed Central  Google Scholar 

  26. Smith EM, Cohen JA, Pett MA, Beck SL (2010) The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums. Cancer Nurs 33(3):173–183. doi:10.1097/NCC.0b013e3181c989a3

    Article  PubMed  Google Scholar 

  27. Postma TJ, Aaronson NK, Heimans JJ, Muller MJ, Hildebrand JG, Delattre JY, Hoang-Xuan K, Lanteri-Minet M, Grant R, Huddart R, Moynihan C, Maher J, Lucey R (2005) The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer 41(8):1135–1139. doi:10.1016/j.ejca.2005.02.012

    Article  CAS  PubMed  Google Scholar 

  28. King MT (1996) The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30. Qual Life Res 5(6):555–567

    Article  CAS  PubMed  Google Scholar 

  29. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376

    Article  CAS  PubMed  Google Scholar 

  30. Caraceni A, Cherny N, Fainsinger R, Kaasa S, Poulain P, Radbruch L, De Conno F (2002) Pain measurement tools and methods in clinical research in palliative care: recommendations of an Expert Working Group of the European Association of Palliative Care. J Pain Symptom Manag 23(3):239–255.

    Article  Google Scholar 

  31. Wildes TM, Dua P, Fowler SA, Miller JP, Carpenter CR, Avidan MS, Stark S (2015) Systematic review of falls in older adults with cancer. J Geriatr Oncol 6(1):70–83. doi:10.1016/j.jgo.2014.10.003

    Article  PubMed  Google Scholar 

  32. Maki BE (1997) Gait changes in older adults: predictors of falls or indicators of fear? J Am Geriatr Soc 45(3):313–320

    Article  CAS  PubMed  Google Scholar 

  33. Kirkwood RN, de Souza Moreira B, Vallone ML, Mingoti SA, Dias RC, Sampaio RF (2011) Step length appears to be a strong discriminant gait parameter for elderly females highly concerned about falls: a cross-sectional observational study. Physiotherapy 97(2):126–131. doi:10.1016/j.physio.2010.08.007

    Article  PubMed  Google Scholar 

  34. Verghese J, Holtzer R, Lipton RB, Wang C (2009) Quantitative gait markers and incident fall risk in older adults. J Gerontol A Biol Sci Med Sci 64(8):896–901. doi:10.1093/gerona/glp033

    Article  PubMed  Google Scholar 

  35. Richardson JK, Thies SB, DeMott TK, Ashton-Miller JA (2004) A comparison of gait characteristics between older women with and without peripheral neuropathy in standard and challenging environments. J Am Geriatr Soc 52(9):1532–1537. doi:10.1111/j.1532-5415.2004.52418.x

    Article  PubMed  Google Scholar 

  36. Richardson JK, Thies SB, DeMott TK, Asthon-Miller JA (2005) Gait analysis in a challenging environment differentiates between fallers and nonfallers among older patients with peripheral neuropathy. Arch Phys Med Rehabil 86:1539–1544

    Article  PubMed  Google Scholar 

  37. Capri G, Munzone E, Tarenzi E, Fulfaro F, Gianni L, Caraceni A, Martini C, Scaioli V (1994) Optic nerve disturbances: a new form of paclitaxel neurotoxicity. J Natl Cancer Inst 86(14):1099–1101

    Article  CAS  PubMed  Google Scholar 

  38. Scaioli V, Caraceni A, Martini C, Curzi S, Capri G, Luca G (2006) Electrophysiological evaluation of visual pathways in paclitaxel-treated patients. J Neurooncol 77(1):79–87. doi:10.1007/s11060-005-9008-x

    Article  CAS  PubMed  Google Scholar 

  39. Argyriou AA, Kyritsis A, Matkatsoris T, Kalofonos HP (2014) Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature. Cancer Manag Res 6:135–147

    Article  PubMed  PubMed Central  Google Scholar 

  40. Nudelman KN, McDonald BC, Wang Y, Smith DJ, West JD, O’Neill DP, Zanville NR, Champion VL, Schneider BP, Saykin AJ (2016) Cerebral perfusion and gray matter changes associated with chemotherapy-induced peripheral neuropathy. J Clin Oncol 34(7):677–683. doi:10.1200/JCO.2015.62.1276

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by the National Cancer Institute (Grant No. R03 CA182165-01) and the National Science Foundation Graduate Research Fellowship Program (Grant No. DGE-1343012). The authors would also like to thank Tatiana Sedlak and Samuel Seelbach for their assistance with analyzing gait videos.

Author information

Author notes

    Authors and Affiliations

    1. Department of Mechanical and Aerospace Engineering, The Ohio State University, 201 W. 19th Ave., Columbus, OH, 43210, USA

      Scott M. Monfort & Ajit M. W. Chaudhari

    2. Center for Biostatistics, The Ohio State University, Columbus, OH, USA

      Xueliang Pan

    3. Stefanie Spielman Comprehensive Breast Center, The Ohio State University, Columbus, OH, USA

      Robyn Patrick

    4. Division of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University, Columbus, OH, USA

      Bhuvaneswari Ramaswamy, Robert Wesolowski & Maryam B. Lustberg

    5. Department of Internal Medicine, The Ohio State University, Columbus, OH, USA

      Michelle J. Naughton

    6. Department of Oncology, Mayo Clinic, Rochester, MN, USA

      Charles L. Loprinzi

    7. School of Health & Rehabilitation Sciences, The Ohio State University, Columbus, OH, USA

      Ajit M. W. Chaudhari

    Authors
    1. Scott M. Monfort
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xueliang Pan
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Robyn Patrick
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Bhuvaneswari Ramaswamy
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Robert Wesolowski
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Michelle J. Naughton
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Charles L. Loprinzi
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Ajit M. W. Chaudhari
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Maryam B. Lustberg
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Scott M. Monfort.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflicts of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

    Informed consent

    Informed consent was obtained from all participants that were included in this study.

    Additional information

    Ajit M. W. Chaudhari and Maryam B. Lustberg are the senior authors with equal contribution.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Online Resource 1 (PDF 104 kb)

    Online Resource 2 (PDF 201 kb)

    Rights and permissions

    Reprints and Permissions

    About this article

    Verify currency and authenticity via CrossMark

    Cite this article

    Monfort, S.M., Pan, X., Patrick, R. et al. Gait, balance, and patient-reported outcomes during taxane-based chemotherapy in early-stage breast cancer patients. Breast Cancer Res Treat 164, 69–77 (2017). https://doi.org/10.1007/s10549-017-4230-8

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10549-017-4230-8

    Keywords

    • Gait
    • Balance
    • Breast cancer
    • CIPN
    • Neuropathies
    • Taxane