Mammographic density as a potential mediator in the association between night shift work and breast cancer risk

Objectives Long-term night shift work is hypothesised to cause changes in mammographic density, which could promote the development of breast cancer. The objective of this study was to explore mammographic density as a mediator in the association between night shift work and breast cancer risk. Methods A population-based case–control study was conducted in Vancouver, Canada between 2005 and 2010. Self-reported occupational histories were used to assess lifetime exposure to night shift work. Mammographic density measures were determined from digitised screening mammograms through Cumulus software for 1719 women (715 cases, 1004 controls). Multivariable logistic and linear regression were used to examine the mediating effect of mammographic density (examined as percent density) in the association between various metrics of night shift work exposure and breast cancer risk. Results Compared with never exposure, ≥20 years of night shift work was associated with a higher risk of breast cancer (total effect OR: 1.75, 95% CI 1.00 to 3.06) and we found evidence that percent density is a mediator in this association (natural indirect effect OR: 1.16, 95% CI 1.02 to 1.35). Estimates for intensity and lifetime cumulative number of night shifts were imprecise but suggested modest elevated risks and possible indirect effects through percent density. Our results were similar when restricting to invasive and hormone-sensitive cancers. Conclusions Our findings support higher mammographic density as a partial mediator in the association between long-term night shift work (≥20 years) and breast cancer risk. Changes in breast density may be one pathway towards increased cancer risk, although larger-scale studies examining multiple time points are needed.