Questions Professionnelles

Quel risque à débuter un traitement par Copaxone en cas d’antécédent de cancer du sein ?

Pr Alain Créange

La sclérose en plaques, avant l’introduction des traitements immunomodulateurs, a été associée à une moindre fréquence de cancer.

Certaines études ont suggéré une augmentation du risque de cancer du sein sous Copaxone (Achiron, Barak et al. 2005) ou d’autres cancers sous interférons et immunosuppresseurs. Cependant ces études restent de méthodologie imparfaite et d’autres n’ont pas confirmé ce risque.

Il existe un risque théorique de lymphome non hodgkinien sous méthotrexate. Il a été évalué à 0,5% sous azathioprine sur une période de 20 ans.

Il existe un risque potentiel de leucémie sous mitoxantrone, de cancer sous cyclophosphamide.

Dans une communication récente à l’American Academy of Neurology, Boston 2007 (Lebrun, Debouverie et al. 2007),  Christine Lebrun et collaborateurs (P06.101 Impact of Modifying Disease Treatments on the Cancer Incidence in Multiple Sclerosis) rapportent une étude rétrospective du risque de cancer en utilisant les données des patients de la base EDMUS et des registres de population de patients atteints de cancer. Elle a observé une prévalence de 1,7% de cancer dans ce groupe de patients, avec une augmentation du risque de cancer du sein, de la vessie et hématologique sous immunosuppresseurs uniquement  (azathioprine, cyclophosphamide and mycophenolate mofetil).

Cette série rétrospective ne donne pas d’élément supplémentaire pour empêcher la prescription de Copaxone en cas d’antécédent de cancer du sein.

Achiron, A., Y. Barak, et al. (2005). "Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments." Breast Cancer Res Treat 89(3): 265-70.

            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, beta-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 beta-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 beta-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 cancer.

Lebrun, C., M. Debouverie, et al. (2007). Impact of Modifying Disease Treatments on the Cancer Incidence in Multiple Sclerosis. American Academy of Neurology, Boston.

           OBJECTIVE: To collect patients with an history of cancer among the 7418 MS  patients gathered from 9 French MS centers. To evaluate impact of diseases  modifying therapies. BACKGROUND: MS has been linked to reduced rates of  cancer prior to the era of immunomodulating (IM) and immunosuppressive (IS)  treatments. Some reports that (i)female MS patients treated with glatiramer acetate  show an elevated rate of breast cancer (ii) patients treated with beta interferons show an elevated risk of non-breast cancers (iii) IS increase risk of cancers  DESIGN/METHODS: Data from French population-based Cancer Registries and EDMUS were used as reference. 4 groups were identified (A)MS without cancer (B)patients with cancer but without IM or IS treatments (C)MS with cancer and IM (D) MS with cancer and IS. RESULTS: 131 patients (1,7%) with MS and cancer were identified:mean age at MS A : 32.5 yrs vs B+C+D : 35 yrs (p<0.01); Age at cancer diagnosis B : 47.7 yrs; C : 29p ; 47.3 yrs ; D: 41.9 yrs (p<0.01). Duration of MS : A : 11.3yrs vs 17.8yrs ; p<0.01. Mean duration of treatments was longer for gp C and D (B : 3.2yrs vs 4.4yrs ; p<0.01) 62.7%of patients had cancer during IM or IS treatments. Standardized incidence ratio was lower for all histologies. IS significantly increase risk of cancer, especially breast, bladder and hematological locations. Results were statistically significant for azathioprine, cyclophosphamide and mycophenolate mofetil (not with mitoxantrone and methotrexate). No link were identified between histologies and IM treatments. CONCLUSIONS/RELEVANCE: It is important to collect patients with history of cancer, to detect potential relations with long-term I or IS treatments.

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