Abstract
Multiple sclerosis (MS) has been linked to reduced rates of cancer prior to the era of immunomodulating treatments. We assessed the incidence of cancer in a cohort of 1338 MS patients and evaluated the effect of exposure to immunomodulatory treatment. Cancer incidence in the MS population was compared with the expected age- and gender-matched incidence rates in the Israeli population for the period 1960–2003. Time-dependant Cox model analysis was used to estimate hazard ratios for glatiramer acetate, β-interferons (1a and 1-b) and intravenous immunoglobulins (IVIg). Among 892 female MS patients, 15 (1.7%) developed breast cancer, and 31 (3.5%) developed cancers of any type. Seventeen of 446 (3.8%) male MS patients developed cancer. The standardized incidence ratios (SIRs) computed until the time of first immunomodulatory treatment were 0.60 (95% CI, 0.38–0.92, p = 0.02) for all female cancer, and 1.11 (95% CI, 0.64–1.91) for all male cancer. Time-dependent covariate analyses for female breast cancer yielded a relative risk for glatiramer acetate of 3.10 (95% CI, 0.86–11.1) and 0.52 (95% CI, 0.07–4.05) for β-interferons. For IVIg, the analyses were uninformative. Our findings indicate that cancer incidence is significantly lower in female MS patients than in the general population. Female MS patients treated with glatiramer acetate showed an elevated rate of breast cancer and all MS patients treated with β-interferons showed an elevated risk of non-breast cancers though not statistically significant (p = 0.122 and 0.072, respectively). Further study is needed to assess possible associations between long-term exposure to the novel immunomodulatory treatments in MS and rate of caner.
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References
TH Ottenhoff (1996) ArticleTitleSelective modulation of T-cell responses in autoimmunity and cancer Immunol Today 17 54–55 Occurrence Handle8808048 Occurrence Handle1:CAS:528:DyaK28XosFChsw%3D%3D
Y Tomer Y Sherer Y Shoenfeld (1998) ArticleTitleAutoantibodies, autoimmunity and cancer Oncol Rep 5 753–761 Occurrence Handle9538189 Occurrence Handle1:CAS:528:DyaK1cXivFKgsLY%3D
Shoenfeld Y, Gershwin ME (eds): Cancer and Autoimmunity. Elsevier publications, 2000, pp 19–111.
RB Lewis CW Castor RE Knisley GG Bole (1976) ArticleTitleFrequency of neoplasia in systemic lupus erythematosus and rheumatoid arthritis Arthritis Rheum 19 1256–1260 Occurrence Handle999736 Occurrence Handle1:STN:280:DyaE2s%2FmsFentA%3D%3D
L Mellemkjaer V Andersen MS Linet G Gridley R Hoover JH Olsen (1997) ArticleTitleNon-Hodgkin’s lymphoma and other cancers among a cohort of patients with systemic lupus erythematosus Arthritis Rheum 40 761–768 Occurrence Handle9125261 Occurrence Handle1:STN:280:DyaK2s3ksVeisA%3D%3D
Y Xu PH Wiernik (2001) ArticleTitleSystemic lupus erythematosus and B-cell hematologic neoplasm Lupus 10 841–850 Occurrence Handle11787873 Occurrence Handle1:STN:280:DC%2BD38%2Fmt1ahsQ%3D%3D
AK Rosenthal JK McLaughlin G Gridley O Nyren (1995) ArticleTitleIncidence of cancer among patients with systemic sclerosis Cancer 76 910–914 Occurrence Handle8625197 Occurrence Handle1:STN:280:DyaK283itlWhsg%3D%3D
JJ Canoso AS Cohen (1974) ArticleTitleMalignancy in a series of 70 patients with systemic lupus erythematosus Arthritis Rheum 17 383–390 Occurrence Handle4604718 Occurrence Handle1:STN:280:DyaE2czgsVagtw%3D%3D
M Lopez Dupla M Khamashta V Pintado Garcia P Lavilla Uriol E Valencia Ortega A Gil Aguado (1993) ArticleTitleMalignancy in systemic lupus erythematosus: a report of five cases in a series of 96 patients Lupus 2 377–380 Occurrence Handle8136821 Occurrence Handle1:STN:280:DyaK2c7osVemsg%3D%3D
O Mutru M Laakso H Isomaki K Koota (1985) ArticleTitleTen year mortality and causes of death in patients with rheumatoid arthritis Br Med J 290 1797–1799 Occurrence Handle1:STN:280:DyaL2M3islajug%3D%3D Occurrence Handle10.1136/bmj.290.6484.1797
E Thomas DH Brewster RJ Black GJ Macfarlane (2000) ArticleTitleRisk of malignancy among patients with rheumatic conditions Int J Cancer 88 497–502 Occurrence Handle11054684 Occurrence Handle1:STN:280:DC%2BD3crgsl2guw%3D%3D
F Wolfe DM Mitchell JT Sibley JF Fries DA Bloch CA Williams PW Spitz M Haga SM Kleinheksel MA Cathey (1994) ArticleTitleThe mortality of rheumatoid arthritis Arthritis Rheum 37 481–494 Occurrence Handle8147925 Occurrence Handle1:STN:280:DyaK2c7pslOrsw%3D%3D
S Jacobsen P Halberg S Ullman (1998) ArticleTitleMortality and causes of death of 344 Danish patients with systemic sclerosis (scleroderma) Br J Rheumatol 37 750–755 Occurrence Handle9714351 Occurrence Handle1:STN:280:DyaK1cznvVWmsQ%3D%3D
GRV Hughes (2001) ArticleTitleLupus patients are protected from cancer Lupus 10 833–834 Occurrence Handle11787871 Occurrence Handle1:STN:280:DC%2BD38%2Fmt1ahsw%3D%3D
A Achiron Y Barak (2000) ArticleTitleMultiple sclerosis-from probable to definite diagnosis: a 7-year prospective study Arch Neurol. 57 974–979 Occurrence Handle10891979 Occurrence Handle1:STN:280:DC%2BD3czltF2msw%3D%3D
IR Cohen (2000) ArticleTitleDiscrimination and dialogue in the immune system Semin Immunol 12 215–219 Occurrence Handle10910742 Occurrence Handle1:STN:280:DC%2BD3cvlsVymtg%3D%3D
IV Allen JH Millar MJ Hutchinson (1978) ArticleTitleGeneral disease in 120 necropsy-proven cases of multiple sclerosis Neuropathol Appl Neurobiol 4 279–284 Occurrence Handle10.1111/j.1365-2990.1978.tb00546.x Occurrence Handle703928 Occurrence Handle1:STN:280:DyaE1M%2Fjt1egtA%3D%3D
N Koch-Henriksen H Bronnum-Hansen E Stenager (1998) ArticleTitleUnderlying cause of death in Danish patients with multiple sclerosis: results from the Danish Multiple Sclerosis Registry J Neurol Neurosurg Psychiatry 65 56–59 Occurrence Handle9667561 Occurrence Handle1:STN:280:DyaK1czjtVWgtw%3D%3D
AD Sadovnick K Eisen GC Ebers DW Paty (1991) ArticleTitleCause of death in patients attending multiple sclerosis clinics Neurology 41 1193–1196 Occurrence Handle1866003 Occurrence Handle1:STN:280:DyaK3Mzis1agtQ%3D%3D
R Midgard E Glattre M Gronning T Riise A Edland H Nyland (1996) ArticleTitleMultiple sclerosis and cancer in Norway. A retrospective cohort study Acta Neurol Scand 93 411–415 Occurrence Handle8836302 Occurrence Handle1:STN:280:DyaK28vjtleitw%3D%3D Occurrence Handle10.1111/j.1600-0404.1996.tb00019.x
H Moller RW Kneller JD Boice JH Olsen (1991) ArticleTitleCancer incidence following hospitalization for multiple sclerosis in Denmark Acta Neurol Scand 84 214–220 Occurrence Handle1950464 Occurrence Handle1:STN:280:DyaK38%2FlslGqtA%3D%3D Occurrence Handle10.1111/j.1600-0404.1991.tb04941.x
J Palo J Duchesne J Wikstrom (1977) ArticleTitleMalignant diseases among patients with multiple sclerosis J Neurol 216 217–222 Occurrence Handle72140 Occurrence Handle1:STN:280:DyaE1c%2FivVWquw%3D%3D
AK Percy FT Nobrega H Okazaki E Glattre T Hurland (1971) ArticleTitleMultiple sclerosis in Rochester, Minn. A 60-year appraisal Arch Neurol 25 105–111 Occurrence Handle5571012 Occurrence Handle1:STN:280:DyaE3M3ptVSltQ%3D%3D
H Bronnum-Hansen N Koch-Henriksen E Stenager (2004) ArticleTitleTrends in survival and cause of death in Danish patients with multiple sclerosis Brain 127 844–850 Occurrence Handle14960501
DS Goodin EM Frohman GP Garmany SuffixJr J Halper WH Likosky FD Lublin DH Silberberg WH Stuart S van den Noort (2002) ArticleTitleTherapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines Neurology 58 169–178 Occurrence Handle1:STN:280:DC%2BD38%2FnvV2htw%3D%3D Occurrence Handle11805241
CM Poser DW Paty L Scheinberg WI McDonald FA Davis GC Ebers KP Johnson WA Sibley DH Silberberg WW Tourtellotte (1983) ArticleTitleNew diagnostic criteria for multiple sclerosis: guidelines for research protocols Ann Neurol 13 227–231 Occurrence Handle1:STN:280:DyaL3s3gt1OgtQ%3D%3D Occurrence Handle6847134
MH Gail (1981) ArticleTitleEvaluating serial cancer marker studies in patients at risk of recurrent disease Biometrics 37 67–78 Occurrence Handle7248444 Occurrence Handle1:STN:280:DyaL3M3jtlWrtQ%3D%3D
DR Cox (1972) ArticleTitleRegression models and life tables (with discussion) J Roy Statist Soc B 34 187–220
Central Bureau of Statistics, Israel: Census of Population and Housing; Publication No. 1, Population and Households, pp 2–74, table 2.23, 2002.
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Achiron, A., Barak, Y., Gail, M. et al. Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments. Breast Cancer Res Treat 89, 265–270 (2005). https://doi.org/10.1007/s10549-004-2229-4
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DOI: https://doi.org/10.1007/s10549-004-2229-4