Background/Purpose: There is an increase in cancer in SLE over-all, but decrease in other cancers, such as breast cancer. Of particular interest are autoantibodies targeting DNA, which may penetrate cells and interfere with DNA repair; these may be lethal to cancer cells and hence protect against breast cancer. Our primary objective was to assess breast cancer risk in females with SLE, comparing patients who test positive for anti-double stranded (ds) DNA antibodies, versus those who do not. We also assessed other demographic and clinical factors.

Methods: We used data from a very large multi-site international SLE cohort. The data presented in this preliminary analysis are from four centres: Toronto, Montreal, Winnipeg, and Baltimore. We used Cox proportional hazards regression to calculate the hazard ratio (HR) for breast cancer risk in female SLE patients, relative to their exposure in terms of anti-dsDNA positivity over time, in models that controlled for time-dependent medication exposures, demographics (age, race/ethnicity), and calendar year. Anti-dsDNA positivity was assessed on the basis of annual SLE Disease Activity Index, SLEDAI scores, assessed at baseline and annually. A weighted average of the number of times patients were anti-dsDNA positive was generated, and we included in our regression model, a time-dependent variable capturing this weighted average. We also included time-dependent measures of cumulative disease activity (adjusted mean SLEDAI scores, modified by removal of the item for anti-dsDNA). Time zero for the observation interval was SLE diagnosis, so that our analyses adjusted for SLE duration. We included cancers occurring after entry into the lupus cohort and up to the time of cohort exit (defined by death or date of last visit).

Results: These analyses include 34 SLE breast cancers cases and 3,391 female SLE patients without any cancer. Compared to controls without cancer, breast cancer cases tended to be white (78% versus 61% in controls), with a trend towards being older at cohort entry (mean 42.8 years, median 43.6; versus mean 38.4, median 36.8 in controls). The same proportion (20.6%) of cases and cancer-free controls were anti-dsDNA positive at cohort entry, and DNA positivity through the observation interval was also similar. Breast cancer cases were similar to cancer-free controls in terms of baseline disease activity and the profile of cumulative drug exposures over time. In both univariate and multivariate models, the principal factors associated with breast cancer risk were older age at cohort entry and calendar year. Of note, anti-malarial use was not demonstrated as a protective factor in these analyses, modelled either as a categorical or continuous (years exposed) variable.

Conclusion: In these preliminary data, we saw no difference in breast cancer risk in females with SLE, comparing patients who are positive for anti-ds DNA serology, versus those who are not. However, our analyses are based on only 34 cases (and 3,391 controls); as well, we have so far only assessed serology and not specifically cell-penetrating autoantibodies (which may be more important). Our analyses also did not establish anti-malarial agents as protective for breast cancer, but here further analyses are also needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/breast-cancer-in-systemic-lupus-sle-do-demographic-and-clinical-factors-including-dna-serology-influence-risk/