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Exercise and health-related fitness predictors of chemotherapy completion in breast cancer patients: pooled analysis of two multicenter trials

Abstract

Purpose

Achieving a higher chemotherapy completion rate is associated with better outcomes in breast cancer patients. We examined the role of exercise and health-related fitness variables in predicting chemotherapy completion in early stage breast cancer patients.

Methods

We pooled data from two large, multicenter, exercise trials that obtained baseline (pre-chemotherapy) measures of exercise and health-related fitness in 543 breast cancer patients initiating adjuvant chemotherapy. Assessments included body composition, cardiovascular fitness, muscular strength, patient-reported physical functioning, and self-reported exercise behavior. Chemotherapy completion was assessed as the average relative dose intensity (RDI) for the originally planned regimen. We used logistic regression analyses with a two-sided p value of < 0.05 to estimate the associations between the predictors and an RDI of ≥ 85%.

Results

Overall, 432 of 543 (79.6%) breast cancer patients received an RDI of ≥ 85%. In logistic regression analyses adjusted for significant covariates, patients in the highest 20% vs. lowest 80% of absolute VO2peak were significantly more likely to complete ≥ 85% RDI (89.0% vs. 77.2%; ORadj 2.06, 95% CI 1.07–3.96, p = 0.031). Moreover, patients in the highest 80% vs. lowest 20% of absolute chest strength were significantly more likely to complete ≥ 85% RDI (81.5% vs. 71.4%; ORadj 1.80, 95% CI 1.09–2.98, p = 0.021).

Conclusions

In these exploratory analyses, higher baseline (pre-chemotherapy) cardiovascular fitness and muscular strength were associated with higher rates of chemotherapy completion in early stage breast cancer patients. Aerobic and/or strength training interventions that increase cardiovascular fitness and muscular strength prior to chemotherapy for breast cancer may improve treatment tolerability and outcomes.

Clinical trial registration

START: NCT00115713, June 24, 2005; CARE: NCT00249015, November 7, 2005 (http://clinicaltrials.gov).

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Abbreviations

BMI:

Body Mass Index

DEXA:

Dual energy X-ray absorptiometry

PWB:

Physical well-being

START:

Supervised Trial of Aerobic versus Resistance Training

UC:

Usual care

CARE:

Combined Aerobic and Resistance Exercise

FWB:

Functional well-being

RDI:

Relative dose intensity

TOI-F:

Trial Outcome Index-Fatigue

References

  1. 1.

    Bland KA, Zadravec K, Landry T, Weller S, Meyers L, Campbell KL (2019) Impact of exercise on chemotherapy completion rate: a systematic review of the evidence and recommendations for future exercise oncology research. Crit Rev Oncol Hematol 136:79–85. https://doi.org/10.1016/j.critrevonc.2019.02.005

    Article  PubMed  Google Scholar 

  2. 2.

    Cespedes Feliciano EM, Chen WY, Lee V, Albers KB, Prado CM, Alexeeff S, Xiao J, Shachar SS, Caan BJ (2020) Body composition, adherence to anthracycline and taxane-based chemotherapy, and survival after nonmetastatic breast cancer. JAMA Oncol 6(2):264–270. https://doi.org/10.1001/jamaoncol.2019.4668

    Article  PubMed  Google Scholar 

  3. 3.

    Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, Mackey JR, Koski S, Pituskin E, Sawyer MB (2009) Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 15(8):2920–2926. https://doi.org/10.1158/1078-0432.CCR-08-2242

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Usiskin I, Li F, Irwin ML, Cartmel B, Sanft T (2019) Association between pre-diagnosis BMI, physical activity, pathologic complete response, and chemotherapy completion in women treated with neoadjuvant chemotherapy for breast cancer. Breast Cancer 26(6):719–728. https://doi.org/10.1007/s12282-019-00974-3

    Article  PubMed  Google Scholar 

  5. 5.

    Zhang L, Yu Q, Wu XC, Hsieh MC, Loch M, Chen VW, Fontham E, Ferguson T (2018) Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2− vs. triple-negative. Breast Cancer Res Treat 169(1):175–187. https://doi.org/10.1007/s10549-017-4646-1

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Courneya KS, Segal RJ, Mackey JR, Gelmon K, Reid RD, Friedenreich CM, Ladha AB, Proulx C, Vallance JK, Lane K, Yasui Y, McKenzie DC (2007) Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol 25(28):4396–4404. https://doi.org/10.1200/JCO.2006.08.2024

    Article  Google Scholar 

  7. 7.

    van Waart H, Stuiver MM, van Harten WH, Geleijn E, Kieffer JM, Buffart LM, de Maaker-Berkhof M, Boven E, Schrama J, Geenen MM, Meerum Terwogt JM, van Bochove A, Lustig V, van den Heiligenberg SM, Smorenburg CH, Hellendoorn-van Vreeswijk JA, Sonke GS, Aaronson NK (2015) Effect of low-intensity physical activity and moderate- to high-intensity physical exercise during adjuvant chemotherapy on physical fitness, fatigue, and chemotherapy completion rates: results of the PACES randomized clinical trial. J Clin Oncol 33(17):1918–1927. https://doi.org/10.1200/JCO.2014.59.1081

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Wyatt G, Sikorskii A, Tesnjak I, Victorson D, Srkalovic G (2015) Chemotherapy interruptions in relation to symptom severity in advanced breast cancer. Support Care Cancer 23(11):3183–3191. https://doi.org/10.1007/s00520-015-2698-5

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Courneya KS, McKenzie DC, Mackey JR, Gelmon K, Friedenreich CM, Yasui Y, Reid RD, Cook D, Jespersen D, Proulx C, Dolan LB, Forbes CC, Wooding E, Trinh L, Segal RJ (2013) Effects of exercise dose and type during breast cancer chemotherapy: multicenter randomized trial. J Natl Cancer Inst 105(23):1821–1832. https://doi.org/10.1093/jnci/djt297

    Article  PubMed  Google Scholar 

  10. 10.

    Eisner MD, Blanc PD, Sidney S, Yelin EH, Lathon PV, Katz PP, Tolstykh I, Ackerson L, Iribarren C (2007) Body composition and functional limitation in COPD. Respir Res 8:7. https://doi.org/10.1186/1465-9921-8-7

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Adams SC, Segal RJ, McKenzie DC, Vallerand JR, Morielli AR, Mackey JR, Gelmon K, Friedenreich CM, Reid RD, Courneya KS (2016) Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast Cancer Res Treat 158(3):497–507. https://doi.org/10.1007/s10549-016-3900-2

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Kelly TL, Wilson KE, Heymsfield SB (2009) Dual energy X-ray absorptiometry body composition reference values from NHANES. PLoS ONE 4(9):e7038. https://doi.org/10.1371/journal.pone.0007038

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E (1997) Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manag 13(2):63–74

    CAS  Article  Google Scholar 

  14. 14.

    Godin G, Shephard RJ (1985) A simple method to assess exercise behavior in the community. Can J Appl Sport Sci 10(3):141–146

    CAS  PubMed  Google Scholar 

  15. 15.

    Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, Schneider CM, von Gruenigen VE, Schwartz AL, American College of Sports Medicine (2010) American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42(7):1409–1426. https://doi.org/10.1249/MSS.0b013e3181e0c112

    Article  PubMed  Google Scholar 

  16. 16.

    Hryniuk W, Bush H (1984) The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol 2(11):1281–1288. https://doi.org/10.1200/JCO.1984.2.11.1281

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Hryniuk WM, Figueredo A, Goodyear M (1987) Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer. Semin Oncol 14(4 Suppl 4):3–11

    CAS  PubMed  Google Scholar 

  18. 18.

    Longo DL, Duffey PL, DeVita VT Jr, Wesley MN, Hubbard SM, Young RC (1991) The calculation of actual or received dose intensity: a comparison of published methods. J Clin Oncol 9(11):2042–2051. https://doi.org/10.1200/JCO.1991.9.11.2042

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C (1995) Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 332(14):901–906. https://doi.org/10.1056/NEJM199504063321401

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    van den Berg MM, Kok DE, Posthuma L, Kamps L, Kelfkens CS, Buist N, Geenen M, Haringhuizen A, Heijns JB, van Lieshout RH (2019) Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I–IIIB breast cancer receiving chemotherapy. Breast Cancer Res Treat 173(2):475–481

    Article  Google Scholar 

  21. 21.

    Gouerant S, Leheurteur M, Chaker M, Modzelewski R, Rigal O, Veyret C, Lauridant G, Clatot F (2013) A higher body mass index and fat mass are factors predictive of docetaxel dose intensity. Anticancer Res 33(12):5655–5662

    CAS  PubMed  Google Scholar 

  22. 22.

    Shachar SS, Deal AM, Weinberg M, Williams GR, Nyrop KA, Popuri K, Choi SK, Muss HB (2017) Body composition as a predictor of toxicity in patients receiving anthracycline and taxane-based chemotherapy for early-stage breast cancer. Clin Cancer Res 23(14):3537–3543. https://doi.org/10.1158/1078-0432.CCR-16-2266

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Jones LW, Liang Y, Pituskin EN, Battaglini CL, Scott JM, Hornsby WE, Haykowsky M (2011) Effect of exercise training on peak oxygen consumption in patients with cancer: a meta-analysis. Oncologist 16(1):112–120. https://doi.org/10.1634/theoncologist.2010-0197

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Collins JT, Noble S, Chester J, Davies HE, Evans WD, Farewell D, Lester JF, Parry D, Pettit R, Byrne A (2018) The value of physical performance measurements alongside assessment of sarcopenia in predicting receipt and completion of planned treatment in non-small cell lung cancer: an observational exploratory study. Support Care Cancer 26(1):119–127. https://doi.org/10.1007/s00520-017-3821-6

    Article  PubMed  Google Scholar 

  25. 25.

    Prado CM, Cushen SJ, Orsso CE, Ryan AM (2016) Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact. Proc Nutr Soc 75(2):188–198. https://doi.org/10.1017/S0029665115004279

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Prado CMM, Heymsfield SB (2014) Lean tissue imaging: a new era for nutritional assessment and intervention. JPEN 38(8):940–953. https://doi.org/10.1177/0148607114550189

    Article  Google Scholar 

  27. 27.

    McGregor RA, Cameron-Smith D, Poppitt SD (2014) It is not just muscle mass: a review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life. Longev Healthspan 3(1):9–9. https://doi.org/10.1186/2046-2395-3-9

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

START and CARE were funded by the Canadian Breast Cancer Research Alliance. K.S. Courneya is supported by the Canada Research Chairs Program. D.W. Kang was supported by an Alberta Innovates Graduate Studentship. C.M. Friedenreich was supported by a Health Senior Scholar award from Alberta Innovates Health Solution and the Alberta Cancer Foundation Weekend to End Women’s Cancers Breast Cancer Chair.

Author information

Affiliations

Authors

Contributions

KYA: Conceptualization, formal analyses, visualization, writing the original draft, and writing review and editing. FZA, DWK, ARM, and SMN: Formal analyses, visualization, writing the original draft, and writing review and editing. CMF, DCM, KG, and JRM: Conceptualization, data curation, funding acquisition, methodology, project administration, resources, supervision, and writing review and editing. KSC: Conceptualization, data curation, formal analyses, funding acquisition, methodology, project administration, resources, supervision, visualization, writing the original draft, and writing review and editing.

Corresponding author

Correspondence to Kerry S. Courneya.

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Conflict of interest

The authors declare that they have no conflict interests.

Ethics approval

In both START and CARE, ethics approval was obtained for all three sites (i.e., the Cross Cancer Institute in Edmonton, Alberta; the Ottawa Hospital Integrated Cancer Program and Cancer Center in Ottawa, Ontario; and the British Columbia Cancer Agency in Vancouver, British Columbia, Canada). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Consent to participate

Informed consent was obtained from all participants in the study.

Consent for publication

Not applicable.

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An, KY., Arthuso, F.Z., Kang, DW. et al. Exercise and health-related fitness predictors of chemotherapy completion in breast cancer patients: pooled analysis of two multicenter trials. Breast Cancer Res Treat 188, 399–407 (2021). https://doi.org/10.1007/s10549-021-06205-8

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Keywords

  • Body composition
  • Breast cancer
  • Exercise
  • Physical fitness
  • Chemotherapy