{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:28:17Z","timestamp":1791419297927,"version":"4.3.3"},"reference-count":54,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C2088201"],"award-info":[{"award-number":["2019R1A2C2088201"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer recurrence is a significant clinical issue in cancer treatment. Psychological stress has been known to contribute to the incidence and progression of cancer; however, its effect on cancer recurrence remains inconclusive. We conducted a systematic review to examine the current evidence from the Medline (PubMed), Embase and Cochrane Library up to May 2021. Among 35 relevant articles, a total of 6 studies (10 data points) were finally selected, which enrolled 26,329 patients (26,219 breast cancer patients except hepatocellular carcinoma patients in 1 study), 4 cohort studies (8 data points) and 2 RCTs (2 data points). Among the 8 data points in cohort studies, four psychological stress-related factors (two \u2018anxiety\u2019, one \u2018depression\u2019, and one \u2018hostility\u2019) were shown to be moderately related with the risk for cancer recurrence, while \u2018loss of partner\u2019 resulted in opposite outcomes. The \u2018emotional\u2018 and \u2018mental\u2019 health factors showed conflicting results, and an RCT-derived meta-analysis proved the positive efficiency of psychotherapies in reducing the cancer recurrence risk among breast cancer patients (HR = 0.52; 95% CI 0.33\u20130.84). Despite the limitations, this study produces comprehensive information about the effect of psychological stress on cancer recurrence and provides reference data to clinicians and scientists for further studies.<\/jats:p>","DOI":"10.3390\/cancers13225816","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T20:58:21Z","timestamp":1637528301000},"page":"5816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["The Risk of Psychological Stress on Cancer Recurrence: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Hyeon-Muk","family":"Oh","sequence":"first","affiliation":[{"name":"College of Korean Medicine, Daejeon University, Daejeon 35235, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Gue","family":"Son","sequence":"additional","affiliation":[{"name":"Liver and Immunology Research Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon 35235, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40880-017-0206-7","article-title":"Cancer metastasis: Issues and challenges","volume":"36","author":"Qian","year":"2017","journal-title":"Chin. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1002\/cam4.2474","article-title":"Are 90% of deaths from cancer caused by metastases?","volume":"8","author":"Rogers","year":"2019","journal-title":"Cancer Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, L. (2017). Early Diagnosis of Breast Cancer. Sensors, 17.","DOI":"10.3390\/s17071572"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1007\/s00520-016-3272-5","article-title":"From normal response to clinical problem: Definition and clinical features of fear of cancer recurrence","volume":"24","author":"Lebel","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/jnci\/djn233","article-title":"Residual Risk of Breast Cancer Recurrence 5 Years After Adjuvant Therapy","volume":"100","author":"Brewster","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1007\/s10350-007-9030-5","article-title":"Follow-Up After Curative Resection of Colorectal Cancer: A Meta-Analysis","volume":"50","author":"Tjandra","year":"2007","journal-title":"Dis. Colon Rectum"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1055\/s-2005-871198","article-title":"Resection and liver transplantation for hepatocellular carcinoma","volume":"25","author":"Llovet","year":"2005","journal-title":"Semin. Liver Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Faisal, M., Abu Bakar, M., Sarwar, A., Adeel, M., Batool, F., Malik, K.I., Jamshed, A., and Hussain, R. (2018). Depth of invasion (DOI) as a predictor of cervical nodal metastasis and local recurrence in early stage squamous cell carcinoma of oral tongue (ESSCOT). PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202632"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/jso.20630","article-title":"Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers","volume":"95","author":"Hoffmann","year":"2007","journal-title":"J. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"671","DOI":"10.4161\/cbt.8.8.7834","article-title":"Detection of circulating tumor Cells in the context of treatment: Prognostic value in breast cancer patients","volume":"8","author":"Serrano","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_12","first-page":"53","article-title":"Psychological Stress and Cancer: New Evidence of An Increasingly Strong Link","volume":"23","author":"Abate","year":"2020","journal-title":"Transl. Med. UniSa"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1200\/JCO.2009.26.9357","article-title":"Host Factors and Cancer Progression: Biobehavioral Signaling Pathways and Interventions","volume":"28","author":"Lutgendorf","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrc3978","article-title":"Sympathetic nervous system regulation of the tumour microenvironment","volume":"15","author":"Cole","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1097\/PSY.0b013e318186fb27","article-title":"Stress Management Intervention Reduces Serum Cortisol and Increases Relaxation During Treatment for Nonmetastatic Breast Cancer","volume":"70","author":"Phillips","year":"2008","journal-title":"Psychosom. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.bbi.2008.08.002","article-title":"Psychological intervention and health outcomes among women treated for breast cancer: A review of stress pathways and biological mediators","volume":"23","author":"McGregor","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_17","unstructured":"(2021, October 18). MD Anderson Cancer Center. Psychiatric Oncology Center. Available online: https:\/\/www.mdanderson.org\/patients-family\/diagnosis-treatment\/care-centers-clinics\/psychiatric-oncology-center.html."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/1270397","article-title":"Psychological Stress and Cellular Aging in Cancer: A Meta-Analysis","volume":"2019","author":"Kruk","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/ncponc1134","article-title":"Do stress-related psychosocial factors contribute to cancer incidence and survival?","volume":"5","author":"Chida","year":"2008","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1007\/s00262-008-0485-6","article-title":"Immune, endocrine, and behavioral precursors to breast cancer recurrence: A case-control analysis","volume":"57","author":"Thornton","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1016\/j.ejca.2008.05.007","article-title":"Environmental risk factors for relapse of melanoma","volume":"44","author":"Beswick","year":"2008","journal-title":"Eur. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1016\/j.respe.2008.12.013","article-title":"Should psychological events be considered cancer risk factors?","volume":"57","author":"Schraub","year":"2009","journal-title":"Rev. D\u2019\u00e9pid\u00e9miol. Sant Publique"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s12609-010-0021-5","article-title":"The Relationship Between Psychosocial Stressors and Breast Cancer Biology","volume":"2","author":"Conzen","year":"2010","journal-title":"Curr. Breast Cancer Rep."},{"key":"ref_24","unstructured":"Wells, G.A., Shea, B., O\u2019connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2021, October 18). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Available online: http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.htm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sterne, J.A.C., Savovi\u0107, J., Page, M., Elbers, R.G., Blencowe, N., Boutron, I., Cates, C., Cheng, H.-Y., Corbett, M.S., and Eldridge, S.M. (2019). RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ, 366.","DOI":"10.1136\/bmj.l4898"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control. Clin. Trials"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s10549-006-9447-x","article-title":"Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients","volume":"105","author":"Groenvold","year":"2007","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/pon.1742","article-title":"Poor physical health predicts time to additional breast cancer events and mortality in breast cancer survivors","volume":"20","author":"Saquib","year":"2011","journal-title":"Psycho-Oncology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/bjc.2012.96","article-title":"Loss of partner and breast cancer prognosis\u2014A population-based study, Denmark, 1994\u20132010","volume":"106","author":"Olsen","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1002\/pon.4305","article-title":"Anxiety and serum catecholamines as predictors of survival and recurrence in hepatocellular carcinoma","volume":"26","author":"Liu","year":"2016","journal-title":"Psycho-Oncology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1002\/cncr.23969","article-title":"Psychologic intervention improves survival for breast cancer patients","volume":"113","author":"Andersen","year":"2008","journal-title":"Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s10549-015-3626-6","article-title":"A randomized controlled trial of cognitive-behavioral stress management in breast cancer: Survival and recurrence at 11-year follow-up","volume":"154","author":"Stagl","year":"2015","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s10597-010-9306-4","article-title":"Factors Associated with Psychological Distress in the Canadian Population: A Comparison of Low-Income and Non Low-Income Sub-Groups","volume":"47","author":"Caron","year":"2010","journal-title":"Community Ment. Health J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1001\/jama.298.14.1685","article-title":"Psychological Stress and Disease","volume":"298","author":"Cohen","year":"2007","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1037\/a0024768","article-title":"Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms","volume":"137","author":"Miller","year":"2011","journal-title":"Psychol. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1093\/annonc\/mdp515","article-title":"Prevalence of mental health conditions in cancer patients in acute care\u2014A meta-analysis","volume":"21","author":"Singer","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/ije\/dyu038","article-title":"The global prevalence of common mental disorders: A systematic review and meta-analysis 1980\u20132013","volume":"43","author":"Steel","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1097\/NCC.0b013e318289a6e2","article-title":"Stressors, Stress Response, and Cancer Recurrence","volume":"37","author":"Todd","year":"2014","journal-title":"Cancer Nurs."},{"key":"ref_40","first-page":"15163","article-title":"Stress and Coping Theories","volume":"22","author":"Krohne","year":"2001","journal-title":"Int. Encycl. Soc. Behav. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Clayton, P.J. (2007). Bereavement. Encyclopedia of Stress, Elsevier inc.. [2nd ed.].","DOI":"10.1016\/B978-012373947-6.00053-2"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1177\/0265407504044838","article-title":"Short-Term Consequences of Severe Marital Stressors","volume":"21","author":"Cano","year":"2004","journal-title":"J. Soc. Pers. Relatsh."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1741-3729.2010.00595.x","article-title":"Stress, Communication, and Marital Quality in Couples","volume":"59","author":"Ledermann","year":"2010","journal-title":"Fam. Relat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"734","DOI":"10.18203\/2394-6040.ijcmph20180259","article-title":"Quality of marital relationship, partner violence, psychological distress, and resilience in women with primary infertility","volume":"5","author":"Satheesan","year":"2018","journal-title":"Int. J. Community Med. Public Health"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/bjc.2012.581","article-title":"Cancer heterogeneity: Implications for targeted therapeutics","volume":"108","author":"Fisher","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.paid.2004.01.010","article-title":"Gender differences in stress and coping styles","volume":"37","author":"Matud","year":"2004","journal-title":"Pers. Individ. Differ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"518","DOI":"10.12968\/ijtr.2010.17.10.78810","article-title":"An overview of cohort study designs and their advantages and disadvantages","volume":"17","author":"Morrow","year":"2010","journal-title":"Int. J. Ther. Rehabil."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/pon.1529","article-title":"Randomized controlled trial of mindfulness-based stress reduction (MBSR) for survivors of breast cancer","volume":"18","author":"Lengacher","year":"2009","journal-title":"Psycho-Oncology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jpsychores.2010.11.010","article-title":"A pilot study of cognitive behavioral stress management effects on stress, quality of life, and symptoms in persons with chronic fatigue syndrome","volume":"70","author":"Lopez","year":"2011","journal-title":"J. Psychosom. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1097\/00006842-200005000-00002","article-title":"Cognitive-Behavioral Stress Management Reduces Serum Cortisol By Enhancing Benefit Finding Among Women Being Treated for Early Stage Breast Cancer","volume":"62","author":"Cruess","year":"2000","journal-title":"Psychosom. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.bbi.2008.09.005","article-title":"Cognitive behavioral stress management effects on psychosocial and physiological adaptation in women undergoing treatment for breast cancer","volume":"23","author":"Antoni","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_52","first-page":"183","article-title":"Effects of a structured psychiatric intervention on immune function of cancer patients","volume":"25","author":"Hosaka","year":"2000","journal-title":"Tokai J. Exp. Clin. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s10608-012-9476-1","article-title":"The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses","volume":"36","author":"Hofmann","year":"2012","journal-title":"Cogn. Ther. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2018","journal-title":"CA A Cancer J. Clin."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/22\/5816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:33:03Z","timestamp":1760167983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/22\/5816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,19]]},"references-count":54,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cancers13225816"],"URL":"https:\/\/doi.org\/10.3390\/cancers13225816","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,19]]}}}