Risk of major autoimmune diseases in female breast cancer patients: A nationwide, population-based cohort study

Autoři: Hsin-Hua Chen aff001;  Ching-Heng Lin aff002;  Der-Yuan Chen aff007;  Wen-Cheng Chao aff002;  Yi-Hsing Chen aff003;  Wei-Ting Hung aff010;  Yin-Yi Chou aff010;  Yi-Da Wu aff010;  Chien-Chih Chen aff001
Působiště autorů: Ph.D. Program in Translational Medicine, National Chung-Hsing University, Taichung, Taiwan, Republic of China aff001;  Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China aff002;  School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China aff003;  Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, Taiwan, Republic of China aff004;  Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan, Republic of China aff005;  Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China aff006;  Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan, Republic of China aff007;  Translational Medicine Laboratory, Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan, Republic of China aff008;  School of Medicine, China Medical University, Taichung, Taiwan, Republic of China aff009;  Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China aff010;  Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China aff011
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222860



Breast cancer is one of the most common malignancies among women. However, there remains no consensus in current literature on the incidence of autoimmune diseases among breast cancer patients. The purpose of this study was to evaluate the risks of major autoimmune diseases (MAD) including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and dermatomyositis (DMtis)/polymyositis (PM) in female breast cancer patients.


Using the Taiwanese National Health Insurance Research Database (NHIRD) records from 2003 to 2013, we identified newly-diagnosed female breast cancer patients and randomly selected females without breast cancer in the period 2007 to 2013 into a control group. We matched the two cohorts using a 1:4 ratio based on age, and the year of index date for comparison of the risk of major autoimmune diseases. We estimated and compared the relative risks of autoimmune diseases in female breast cancer patients and females without breast cancer.


A total of 54,311 females with breast cancer and 217,244 matched females without breast cancer were included in this study. For SLE, the incidence rates were 2.3 (breast cancer group) vs. 10.0 (control group) per 100,000 women years; for RA rates were 19.3 (breast cancer group) vs. 42.7 (control group) per 100,000 women years; and for SS rates were 20.5 (breast cancer group) vs. 38.2 (control group) per 100,000 women years. After adjusting for potential confounders, the hazard ratios (95% confidence intervals) for female breast cancer patients vs. control group were 0.04 (0.01–0.24) for SLE; 0.03 (0.02–0.04) for RA; and 0.21 (0.09–0.48) for SS.


Female breast cancer patients had lower risks of SLE, RA and SS when compared to female individuals without breast cancer. However, there was no significant difference in the risk of developing DMtis/PM between both groups.

Klíčová slova:

Medicine and health sciences – Oncology – Cancers and neoplasms – Breast tumors – Breast cancer – Cancer treatment – Cancer chemotherapy – Clinical oncology – Clinical medicine – Clinical immunology – Autoimmune diseases – Lupus erythematosus – Systemic lupus erythematosus – Immunology – Rheumatology – Arthritis – Rheumatoid arthritis – Pharmaceutics – Drug therapy – Hormonal therapy – Chemotherapy – Diagnostic medicine – Cancer detection and diagnosis – Biology and life sciences


1. See LC, Kuo CF, Chou IJ, Chiou MJ, Yu KH. Sex-andage-specific incidence of autoimmune rheumatic diseases in the Chinese population: A Taiwan population-based study. Semin Arthritis Rheum. 2013;43:381–386. doi: 10.1016/j.semarthrit.2013.06.001 23916348.

2. Jaberipour M, Habibagahi M, Hosseini A, Habibabad SR, Talei A, Ghaderi A. Increased CTLA-4 and FOXP3 transcripts in peripheral blood mononuclear cells of patients with breast cancer. Pathol Oncol Res. 2010;16(4):547–51. doi: 10.1007/s12253-010-9256-8 20306312.

3. Mao H, Zhang L, Yang Y, Zuo W, Bi Y, Gao W, et al. New insights of CTLA-4 into its biological function in breast cancer. Curr Cancer Drug Targets. 2010;10(7):728–36. https://doi.org/10.2174/156800910793605811 20578982.

4. Khalife E, Khodadadi A, Talaeizadeh A, Rahimian L, Nemati M, Jafarzadeh A. Overexpression of Regulatory T Cell-Related Markers (FOXP3, CTLA-4 and GITR) by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer. Asian Pac J Cancer Prev. 2018;19(11):3019–25. doi: 10.31557/APJCP.2018.19.11.3019 30484986

5. Van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS. CD4+CD25+ regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum 2004;50:2775–85. doi: 10.1002/art.20499 15457445.

6. Scheinecker C, Bonelli M, and Smolen JS. Pathogenetic aspects of systemic lupus erythematosus with an emphasis on regulatory T cells. Journal of Autoimmunity 2010;35: 269–275. doi: 10.1016/j.jaut.2010.06.018 20638240.

7. Tao JH, Cheng M, Tang JP, Liu Q, Pan F, Li XP. Foxp3, Regulatory T Cell, and Autoimmune Diseases. Inflammation. 2017;40:328–339. doi: 10.1007/s10753-016-0470-8 27882473.

8. Lin X, Rui K, Deng J, Tian J, Wand X, Wang S, et al. Th17 cells play a critical role in the development of experimental Sjögren's syndrome. Ann Rheum Dis. 2015; 74:1302–1310. doi: 10.1136/annrheumdis-2013-204584 24573745.

9. Pontarini E, Lucchesi D, and Bombardieri. Current views on the pathogenesis of Sjögren's syndrome. Curr Opin Rheumatol. 2018;30:215–221. doi: 10.1097/BOR.0000000000000473 29227354.

10. Venalis P, and Lundberg IE. Immune mechanisms in polymyositis and dermatomyositis and potential targets for therapy. Rheumatology. 2014;53:397–405. doi: 10.1093/rheumatology/ket279 23970542.

11. Fasth AE, Dastmalchi M, Rahbar A, Salomonsson S, Pandya JM, Lindroos E, et al. T cell infiltrates in the muscles of patients with dermatomyositis and lymyositis are dominated by CD28null T cells. J Immunol 2009;183:4792–4799. doi: 10.4049/jimmunol.0803688 19752224.

12. Zhu T, Keirns J, Howieson C, Kaibara A, Goldwater R, Kivitz AJ, et al. Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients. Clin Pharmacol Drug Dev. 2016;5:408–425. doi: 10.1002/cpdd.251 27410490.

13. Tjarnlund A, Tang Q, Wick C, Dastmalchi M, Mann H, Tomasova Studynkova J, et al. Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial. Ann Rheum Dis. 2018;77:55–62. doi: 10.1136/annrheumdis-2017-211751 28993346.

14. Mease PJ, Gottlieb AB, van der Heijde D, FitzGerald O, Johnsen A, Nys M, et al. Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis. Ann Rheum Dis. 2017;76:1550–1558. doi: 10.1136/annrheumdis-2016-210724 28473423.

15. Blair HA and Deeks ED. Abatacept: A Review in Rheumatoid Arthritis. Drugs. 2017;77:1221–1233. doi: 10.1007/s40265-017-0775-4 28608166.

16. Chow WH, Gridley G, Mellemkjaer L, McLaughlin JK, Olsen JH, Fraumeni JF Jr. Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark. Cancer Causes Control. 1995;6:9–13. https://doi.org/10.1007/BF00051675 7718740.

17. Chen D, Yuan S, Wu X, Li H, Qiu Q, Zhan Z, et al. Incidence and predictive factors for malignancies with dermatomyositis: a cohort from southern China. Clin Exp Rheumatol. 2014;32:615–621. 25068842.

18. Sigurgeirsson B, Lindelöf B, Edhag O, Allander E. Risk of cancer in patients with dermatomyositis or polymyositis. A population-based study. N Engl J Med. 1992;326:363–367. doi: 10.1056/NEJM199202063260602 1729618.

19. Kuo CF, See LC, Yu KH, Chou IJ, Chang HC, Chiou MJ, et al. Incidence, cancer risk and mortality of dermatomyositis and polymyositis in Taiwan: a nationwide population study. Br J Dermatol. 2011;165:1273–1279. doi: 10.1111/j.1365-2133.2011.10595.x 21895620.

20. Fang YF, Wu YJ, Kuo CF, Luo SF, Yu KH. Malignancy in dermatomyositis and polymyositis: analysis of 192 patients. Clin Rheumatol. 2016;35:1977–1984. doi: 10.1007/s10067-016-3296-8 27210465.

21. Cheng TM. Taiwan's new National Health Insurance program: genesis and experience so far. Health Aff (Millwood). 2003;22:61–76. doi: 10.1377/hlthaff.22.3.61 12757273.

22. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J clin epidemiol. 1992;45:613–619. doi: 10.1016/0895-4356(92)90133-8 1607900.

23. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373:23–34. doi: 10.1056/NEJMoa1504030 26027431.

24. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15:700–712. doi: 10.1016/S1470-2045(14)70189-5 24831977.

25. Hengstman GJ, Brouwer R, Egberts WT, Seelig HP, Jongen PJ, van Venrooij WJ, et al. Clinical and serological characteristics of 125 Dutch myositis patients. Myositis specific autoantibodies aid in the differential diagnosis of the idiopathic inflammatory myopathies. J Neurol. 2002;249:69–75. doi: 10.1007/pl00007850 11954871.

26. Marguerie C, Bunn CC, Beynon HL, Bernstein RM, Hughes JM, So AK, et al. Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. Q J Med. 1990;77:1019–1038. https://doi.org/10.1093/qjmed/77.1.1019 2267280.

27. Engel AG, Arahata K. Monoclonal antibody analysis of mononuclear cells in myopathies. II: phenotypes of autoinvasive cells in polymyositis and inclusion body myositis. Ann Neurol. 1984;16:209–215. doi: 10.1002/ana.410160207 6089646.

28. Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH, et al. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore). 1991;70:360–374. doi: 10.1097/00005792-199111000-00002 1659647.

29. Betteridge ZE, Gunawardena H, McHugh NJ. Novel autoantibodies and clinical phenotypes in adult and juvenile myositis. Arthritis Res Ther. 2011;13:209. doi: 10.1186/ar3275 21457520.

30. Rutjes SA, Vree Egberts WT, Jongen P, Van Den Hoogen F, Pruijn GJ, Van Venrooij WJ. Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy. Clin Exp Immunol. 1997;109:32–40. doi: 10.1046/j.1365-2249.1997.4081308.x 9218821.

31. Selva-O’Callaghan A, Labrador-Horrillo M, Solans-Laque R, Simeon-Aznar CP, Martinez-Gomez X, Vilardell-Tarres M. Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy. Arthritis Rheum. 2006;55:791–798. doi: 10.1002/art.22237 17013837.

32. Shah AA, Rosen A, Hummers LK, May BJ, Kaushiva A, Roden RBS, et al. Evaluation of cancer-associated myositis and scleroderma autoantibodies in breast cancer patients without rheumatic disease. Clin Exp Rheumatol. 2017;35:71–74. 28628466.

Článek vyšel v časopise


2019 Číslo 9

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Ulcerative colitis_muž_břicho_střeva
Ulcerózní kolitida
nový kurz

Blokátory angiotenzinových receptorů (sartany)
Autoři: MUDr. Jiří Krupička, Ph.D.

Antiseptika a prevence ve stomatologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Citikolin v neuroprotekci a neuroregeneraci: od výzkumu do klinické praxe nejen očních lékařů
Autoři: MUDr. Petr Výborný, CSc., FEBO

Zánětlivá bolest zad a axiální spondylartritida – Diagnostika a referenční strategie
Autoři: MUDr. Monika Gregová, Ph.D., MUDr. Kristýna Bubová

Všechny kurzy