Abstract
The lower all-cause mortality in women with Ductal carcinoma in situ (DCIS) compared with the general population has been hypothesized to be due to a "healthy-user effect," but this has not been studied in large cohorts. In a population-based, retrospective cohort study comprising 18,942 women with primary DCIS between 1999 and 2015 in the Netherlands, the cumulative incidence of breast cancer death (BCD) was estimated using death by other cause as a competing risk. The cause-specific mortality risk of women with DCIS was compared with that of the Dutch female population. Multivariable competing risk regression was used to quantify the effects of the method of detection and socio-economic status (SES). With 289 BCDs, the 10-year cumulative incidence of BCD was 1.3% (95% CI, 1.1-1.5). Compared to the Dutch female population, women with DCIS had a 2.1-times higher risk of BCD, but a 7% lower risk of all-cause mortality. Women with screen-detected DCIS had lower risks of BCD compared to women with non-screen-detected DCIS (subdistribution hazard ratio [sHR]:0.60, 95% CI 0.47-0.77), as did women with high SES versus low SES (sHR 0.54, 95% CI 0.30-0.97) in the first 4 years of follow-up, adjusted for age and year at diagnosis, and DCIS characteristics. In conclusion, overall mortality in women with DCIS is not higher compared to the Dutch female population, though death due to invasive breast cancer is increased. Within all women with DCIS, those with screen-detected DCIS or high SES had lower BCD and all-cause mortality, suggesting a healthy-user effect.