Fatigue and associated factors among middle-aged patients with breast cancer undergoing chemotherapy in China: A cross-sectional study

Abstract

Background:Fatigue is a prevalent and burdensome symptom in patients with breast cancer undergoing chemotherapy, and middle-aged women may be especially vulnerable.
Objective:To explore fatigue levels and the key factors associated with fatigue in middle-aged patients with breast cancer undergoing chemotherapy.
Study design: A cross-sectional study.
Methods:This multicenter, cross-sectional study was conducted between August 2022 and November 2023. Patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form 8a to assess fatigue, anxiety, depression, sleep disturbance, and pain interference. Univariate tests, Pearson’s correlation analysis, and hierarchical linear regression were used to identify the influencing factors.
Results:A total of 651 patients from two tertiary hospitals in Shanghai and Guangxi were included. The mean fatigue score was 49.4 ± 7.4, with 21.2 % of the patients experiencing mild or more fatigue. The results of hierarchical linear regression analysis showed that absence of medical insurance coverage (b = 0.073, P = 0.010), the period from 3 months to 1 year in the disease course (b = 0.073, P = 0.047), undergoing the fourth or higher cycle of chemotherapy (b = 0.071, P = 0.040), depression (b = 0.605, P < 0.001), and pain interference (b = 0.231, P < 0.001) were positively associated with fatigue, while the third chemotherapy cycle (b = -0.096, P = 0.002) was negatively associated with fatigue. All these variables in the model explained 54.9 % of the variance in fatigue, with depression and pain interference alone accounting for 46.7 % of the variance.
Conclusions:Middle-aged patients with breast cancer undergoing chemotherapy in China had a relatively low percentage of and usually mild levels of fatigue. Interventions targeting depression and pain may effectively alleviate fatigue in this population.

Keywords

Breast cancer / Chemotherapy / Middle-aged / Fatigue / Symptom

CRediT authorship contribution statement

Qi Sun: Writing - original draft. Yi Chen: Writing - original draft. Jiaojiao Zhang: Writing - original draft. Jialin Chen: Writing - original draft. Tingting Zhou: Writing - original draft, Methodology, Investigation, Conceptualization. Yiwen Duan: Writing - original draft, Methodology, Formal analysis, Conceptualization. Changrong Yuan: Writing - review & editing, Funding acquisition. Tingting Cai: Writing - review & editing, Funding acquisition. All authors have read and approved the final version of the manuscript.

Ethics approval

This study was conducted in accordance with the Declaration of Helsinki (2013 revision) and was approved by the Institutional Review Board of Fudan University Shanghai Cancer Center (approval number: 1810192-22) and the Ethics Committee of the Second Affiliated Hospital of Guilin Medical University (approval number: HXXM-2023003). Written informed consent was obtained from all participants prior to enrollment.

Funding

This research was supported by the National Natural Science Foundation of China [grant number 72504060] and the Ministry of Education of Humanities and Social Science Project [grant number 23YJC630002].

Declaration of Competing Interest

Changrong Yuan is an editorial board member of Healthcare and Rehabilitation but has not been involved in the journal’s review or decisions related to this manuscript. The authors declare no conflict of interest.

Acknowledgments

The authors sincerely thank all participants for their time and contributions to this study.

Appendix A. Supplementary material

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.hcr.2025.100050.

Data availability

The data presented in this paper are available from the corresponding author on reasonable request.

References

[1] Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022; 135(5):584-590. https://doi.org/10.1097/CM9.0000000000002108

[2] Li N, Deng Y, Zhou L, et al. Global burden of breast cancer and attributable risk factors in 195 countries and territories, from 1990 to 2017: results from the global burden of disease study 2017. J Hematol Oncol. 2019; 12(1):140. https://doi.org/10.1186/s13045-019-0828-0

[3] Li J, Zhang BN, Fan JH, et al. A nation-wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in China. BMC Cancer. 2011;11:364. https://doi.org/10.1186/1471-2407-11-364

[4] Leong SP, Shen ZZ, Liu TJ, et al. Is breast cancer the same disease in asian and Western countries? World J Surg. 2010; 34(10):2308-2324. https://doi.org/10.1007/s00268-010-0683-1

[5] Iddrisu M, Aziato L, Dedey F. Psychological and physical effects of breast cancer diagnosis and treatment on young Ghanaian women: a qualitative study. BMC Psychiatry. 2020; 20(1):353. https://doi.org/10.1186/s12888-020-02760-4

[6] Chen X, Yan Q, Tang Y, Zhu J, Zhang W, Zhang J. Financial toxicity, family resilience and negative emotions among young and middle-aged breast cancer patients: a multicentre cross-sectional study. Breast. 2024;75:103735. https://doi.org/10.1016/j.breast.2024.103735

[7] Champion VL, Wagner LI, Monahan PO, et al. Comparison of younger and older breast cancer survivors and age-matched controls on specific and overall quality of life domains. Cancer. 2014; 120(15):2237-2246. https://doi.org/10.1002/cncr.28737

[8] Cai T, Zhou T, Chen J, Huang Q, Yuan C, Wu F. Identification of age differences in cancer-related symptoms in women undergoing chemotherapy for breast cancer in China. BMC Women’s Health. 2023; 23(1):100. https://doi.org/10.1186/s12905-023-02256-9

[9] Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical nutrition in cancer. Clin Nutr. 2021; 40(5):2898-2913. https://doi.org/10.1016/j.clnu.2021.02.005

[10] Schmidt ME, Scherer S, Wiskemann J, Steindorf K. Return to work after breast cancer: the role of treatment-related side effects and potential impact on quality of life. Eur J Cancer Care(Engl). 2019; 28(4):e13051. https://doi.org/10.1111/ecc.13051

[11] Cella D, Peterman A, Passik S, Jacobsen P, Breitbart W. Progress toward guidelines for the management of fatigue. Oncology (Williston Park, NY). 1998; 12(11A):369-377.

[12] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Cancer-Related Fatigue. Version 2.2025. Published 2025. Accessed 10 September 2025. 〈https://www.nccn.org/professionals/physician_gls/pdf/fatigue.pdf〉.

[13] Ma Y, He B, Jiang M, et al. Prevalence and risk factors of cancer-related fatigue: a systematic review and meta-analysis. Int J Nurs Stud. 2020;111:103707. https://doi.org/10.1016/j.ijnurstu.2020.103707

[14] Jacobsen PB, Hann DM, Azzarello LM, Horton J, Balducci L, Lyman GH. Fatigue in women receiving adjuvant chemotherapy for breast cancer: characteristics, course, and correlates. J Pain Symptom Manag. 1999; 18(4):233-242. https://doi.org/10.1016/s0885-3924(99)00082-2

[15] De Jong N, Candel MJ, Schouten HC, Abu-Saad HH, Courtens AM. Prevalence and course of fatigue in breast cancer patients receiving adjuvant chemotherapy. Ann Oncol. 2004; 15(6):896-905. https://doi.org/10.1093/annonc/mdh229

[16] Berger AM, Mooney K, Alvarez-Perez A, et al. Cancer-related fatigue, version 2.2015. J Natl Compr Canc Netw. 2015; 13(8):1012-1039. https://doi.org/10.6004/jnccn.2015.0122

[17] Holley S. Cancer-related fatigue. Suffering a different fatigue. Cancer Pract. 2000; 8(2):87-95. https://doi.org/10.1046/j.1523-5394.2000.82007.x

[18] Hajj A, Chamoun R, Salameh P, et al. Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors. BMC Cancer. 2022; 22(1):16. https://doi.org/10.1186/s12885-021-09072-0

[19] Chou YH, Chia-Rong Hsieh V, Chen X, Huang TY, Shieh SH. Unmet supportive care needs of survival patients with breast cancer in different cancer stages and treatment phases. Taiwan J Obstet Gynecol. 2020; 59(2):231-236. https://doi.org/10.1016/j.tjog.2020.01.010

[20] Roila F, Fumi G, Ruggeri B, et al. Prevalence, characteristics, and treatment of fatigue in oncological cancer patients in Italy: a cross-sectional study of the Italian network for supportive care in cancer (NICSO). Support Care Cancer. 2019; 27(3):1041-1047. https://doi.org/10.1007/s00520-018-4393-9

[21] Thong MSY, Van Noorden CJF, Steindorf K, Arndt V. Cancer-Related fatigue: causes and current treatment options. Curr Treat Options Oncol. 2020; 21(2):17. https://doi.org/10.1007/s11864-020-0707-5

[22] Haque R, Hsu JW, Avila C, Olmstead R, Carroll JE, Irwin MR. Insomnia and susceptibility to depressive symptoms and fatigue in diverse breast cancer survivors. J Women’s Health(Larchmt). 2021; 30(11):1604-1615. https://doi.org/10.1089/jwh.2019.8135

[23] He X, Ng MSN, Choi KC, So WKW. Effects of a 16-week dance intervention on the symptom cluster of fatigue-sleep disturbance-depression and quality of life among patients with breast cancer undergoing adjuvant chemotherapy: a randomized controlled trial. Int J Nurs Stud. 2022;133:104317. https://doi.org/10.1016/j.ijnurstu.2022.104317

[24] Tao L, Lv J, Zhong T, et al. Effects of sleep disturbance, cancer-related fatigue, and psychological distress on breast cancer patients’ quality of life: a prospective longitudinal observational study. Sci Rep. 2024; 14(1):8632. https://doi.org/10.1038/s41598-024-59214-0

[25] Li H, Xiong Y, Zhang Q, et al. The interplay between sleep and cancer-related fatigue in breast cancer: a casual and computer-simulated network analysis. Asia Pac J Oncol Nurs. 2025;12:100692. https://doi.org/10.1016/j.apjon.2025.100692

[26] Hendy A, Ibrahim RK, Darwish A, et al. Sleep disturbance, cancer-related fatigue, and depression as determinants of quality of life among breast cancer patients undergoing chemotherapy: a cross-sectional study. BMC Cancer. 2025; 25(1):1122. https://doi.org/10.1186/s12885-025-14538-6

[27] Vaz-Luis I, Di Meglio A, Havas J, et al. Long-term longitudinal patterns of patient- reported fatigue after breast cancer: a group-based trajectory analysis. J Clin Oncol. 2022; 40(19):2148-2162. https://doi.org/10.1200/JCO.21.01958

[28] Qi Y, Li H, Guo Y, Cao Y, Wong CL. Symptom clusters in breast cancer patients receiving adjuvant chemotherapy: a systematic review. J Clin Nurs. 2024; 33(12):4554-4567. https://doi.org/10.1111/jocn.17479

[29] Zhou K, Bellanger M, Le Lann S, Robert M, Frenel JS, Campone M. The predictive value of patient-reported outcomes on the impact of breast cancer treatment-related quality of life. Front Oncol. 2022;12:925534. https://doi.org/10.3389/fonc.2022.925534

[30] VanVoorhis CW, Morgan BL. Understanding power and rules of thumb for determining sample sizes. Tut Quant Methods Psychol. 2007; 3(2):43-50. https://doi.org/10.20982/tqmp.03.2.p043

[31] Cai T, Wu F, Huang Q, et al. Validity and reliability of the Chinese version of the Patient-Reported outcomes measurement information system adult profile-57 (PROMIS-57). Health Qual Life Outcomes. 2022; 20(1):95. https://doi.org/10.1186/s12955-022-01997-9

[32] Kamudoni P, Johns J, Cook KF, et al. Standardizing fatigue measurement in multiple sclerosis: the validity, responsiveness and score interpretation of the PROMIS SF v1.0 - fatigue (MS) 8a. Mult Scler Relat Disord. 2021;54:103117. https://doi.org/10.1016/j.msard.2021.103117

[33] D'Souza A, Magnus BE, Myers J, Dispenzieri A, Flynn KE. The use of PROMIS patient- reported outcomes (PROs) to inform light chain (AL) amyloid disease severity at diagnosis. Amyloid. 2020; 27(2):111-118. https://doi.org/10.1080/13506129.2020.1713743

[34] HealthMeasures. PROMIS Reference Population. Accessed 23 April 2025.〈https://www.healthmeasures.net/score-and-interpret/interpret-scores/promis/reference-populations〉; 2025.

[35] HealthMeasures. PROMIS Score Cut Points. Accessed 23 April 2025.〈https://www.healthmeasures.net/score-and-interpret/interpret-scores/promis/promis-score-cut-points〉; 2025.

[36] Cella D, Choi S, Garcia S, et al. Setting standards for severity of common symptoms in oncology using the PROMIS item banks and expert judgment. Qual Life Res. 2014; 23(10):2651-2661. https://doi.org/10.1007/s11136-014-0732-6

[37] De Jong N, Courtens AM, Abu-Saad HH, Schouten HC. Fatigue in patients with breast cancer receiving adjuvant chemotherapy: a review of the literature. Cancer Nurs. 2002; 25(4):283-299. https://doi.org/10.1097/00002820-200208000-00004

[38] Uslu A, Canbolat O. Relationship between frailty and fatigue in older cancer patients. Semin Oncol Nurs. 2021; 37(4):151179. https://doi.org/10.1016/j.soncn.2021.151179

[39] Levkovich I, Cohen M, Alon S, et al. Symptom cluster of emotional distress, fatigue and cognitive difficulties among young and older breast cancer survivors: the mediating role of subjective stress. J Geriatr Oncol. 2018; 9(5):469-475. https://doi.org/10.1016/j.jgo.2018.05.002

[40] Gnerlich JL, Deshpande AD, Jeffe DB, Sweet A, White N, Margenthaler JA. Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease. J Am Coll Surg. 2009; 208(3):341-347. https://doi.org/10.1016/j.jamcollsurg.2008.12.001

[41] Rossi L, Mazzara C, Pagani O. Diagnosis and treatment of breast cancer in young women. Curr Treat Options Oncol. 2019; 20(12):86. https://doi.org/10.1007/s11864-019-0685-7

[42] Choi E, Henneghan AM. Comparing fatigue, loneliness, daytime sleepiness, and stress in younger and older breast cancer survivors: a Cross-Sectional analysis. Clin J Oncol Nurs. 2022; 26(2):155-164. https://doi.org/10.1188/22.CJON.155-164

[43] Cai T, Zhou T, Huang Q, Wu F, Ni F, Yuan C. Cancer-related symptoms among young and middle-aged women undergoing chemotherapy for breast cancer: application of latent class analysis and network analysis. Eur J Oncol Nurs. 2023;63:102287. https://doi.org/10.1016/j.ejon.2023.102287

[44] Paltrinieri S, Fugazzaro S, Bertozzi L, et al. Return to work in european cancer survivors: a systematic review. Support Care Cancer. 2018; 26(9):2983-2994. https://doi.org/10.1007/s00520-018-4270-6

[45] Alnaim L. Health-related quality of life in women with breast cancer undergoing treatment with hormonal therapy: a review study. Eur J Breast Health. 2022; 18(4):292-298. https://doi.org/10.4274/ejbh.galenos.2022.2022-5-8

[46] Bodelon C, Masters M, Bloodworth DE, et al. Physical health decline after chemotherapy or endocrine therapy in breast cancer survivors. JAMA Netw Open. 2025; 8(2):e2462365. https://doi.org/10.1001/jamanetworkopen.2024.62365

[47] Bower JE, Wiley J, Petersen L, Irwin MR, Cole SW, Ganz PA. Fatigue after breast cancer treatment: biobehavioral predictors of fatigue trajectories. Health Psychol. 2018; 37(11):1025-1034. https://doi.org/10.1037/hea0000652

[48] Berger AM. Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy. Oncol Nurs Forum. 1998; 25(1):51-62.

[49] Schmidt ME, Wiskemann J, Schneeweiss A, Potthoff K, Ulrich CM, Steindorf K. Determinants of physical, affective, and cognitive fatigue during breast cancer therapy and 12 months follow-up. Int J Cancer. 2018; 142(6):1148-1157. https://doi.org/10.1002/ijc.31138

[50] He X, Ng M, Choi K, et al. Synergistic interactions among fatigue, sleep disturbance, and depression in women with breast cancer: a Cross-Sectional study. Oncol Nurs Forum. 2022; 49(3):243-254. https://doi.org/10.1188/22.ONF.243-254

[51] Li MY, Yao LQ, Liu XL, Tan JB, Wang T. Effects of nonpharmacological interventions on symptom clusters in breast cancer survivors: a systematic review of randomized controlled trials. Asia Pac J Oncol Nurs. 2024; 11(3):100380. https://doi.org/10.1016/j.apjon.2024.100380

[52] Yao LQ, Kwok SWH, Tan JB, et al. The effect of an evidence-based tai chi intervention on the fatigue-sleep disturbance-depression symptom cluster in breast cancer patients: a preliminary randomised controlled trial. Eur J Oncol Nurs. 2022;61:102202. https://doi.org/10.1016/j.ejon.2022.102202

[53] Park S, Sato Y, Takita Y, et al. Mindfulness-Based cognitive therapy for psychological distress, fear of cancer recurrence, fatigue, spiritual Well-Being, and quality of life in patients with breast Cancer-A randomized controlled trial. J Pain Symptom Manag. 2020; 60(2):381-389. https://doi.org/10.1016/j.jpainsymman.2020.02.017

[54] 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. 2017; 25(12):3607-3643. https://doi.org/10.1007/s00520-017-3824-3

[55] Miaskowski C, Paul SM, Cooper B, et al. Identification of patient subgroups and risk factors for persistent arm/shoulder pain following breast cancer surgery. Eur J Oncol Nurs. 2014; 18(3):242-253. https://doi.org/10.1016/j.ejon.2013.12.002

[56] Charalambous A, Giannakopoulou M, Bozas E, Paikousis L. Parallel and serial mediation analysis between pain, anxiety, depression, fatigue and nausea, vomiting and retching within a randomised controlled trial in patients with breast and prostate cancer. BMJ Open. 2019; 9(1):e026809. https://doi.org/10.1136/bmjopen-2018-026809

[57] Álvarez-Salvago F, Figueroa-Mayordomo M, Molina-García C, et al. Assessing the relationship of different levels of pain to the health status of Long-Term breast cancer survivors: a Cross-Sectional study. Life(Basel). 2025; 15(2):177. https://doi.org/10.3390/life15020177

[58] Chan RJ, Gordon LG, Tan CJ, et al. Relationships between financial toxicity and symptom burden in cancer survivors: a systematic review. J Pain Symptom Manag. 2019; 57(3):646-660.e1. https://doi.org/10.1016/j.jpainsymman.2018.12.003

[59] Tran TB, Malhotra G, Razavi M, et al. Emotional distress and financial toxicity in younger adult patients undergoing oncologic surgery. Ann Surg. 2022; 276(4):694-700. https://doi.org/10.1097/SLA.0000000000005593

[60] Alexander S, Minton O, Stone PC. Evaluation of screening instruments for cancer- related fatigue syndrome in breast cancer survivors. J Clin Oncol. 2009; 27(8):1197-1201. https://doi.org/10.1200/JCO.2008.19.1668

[61] Junghaenel DU, Cohen J, Schneider S, Neerukonda AR, Broderick JE. Identification of distinct fatigue trajectories in patients with breast cancer undergoing adjuvant chemotherapy. Support Care Cancer. 2015; 23(9):2579-2587. https://doi.org/10.1007/s00520-015-2616-x

[62] Whisenant M, Wong B, Mitchell SA, Beck SL, Mooney K. Distinct trajectories of fatigue and sleep disturbance in women receiving chemotherapy for breast cancer. Oncol Nurs Forum. 2017; 44(6):739-750. https://doi.org/10.1188/17.ONF.739-750