A Quasi-experimental Study of General Practices’ Referral to Mammography in the Posttrial Treatment Era

Background: Improvements in breast cancer therapy since the randomized controlled trials of mammography screening might have reduced the screening benefit. Most observational studies of mammography effectiveness would be confounded by these improvements and other factors. Using a design resistant to this confounding, we evaluated whether mammography in asymptomatic women reduces breast cancer mortality during the treatment era succeeding the trials. Methods: We designed a quasi-experimental cohort study in regions of Denmark without organized screening. We predicted the number of expected mammograms for each general practice based on observed numbers of mammograms and individual risk factors. Regardless of a woman’s individual exposure to mammography, we assigned her the ratio of observed to expected mammograms of her general practice as her instrumental variable. We employed this potential instrumental variable as mammography exposure status and followed women from 1 January 2006 until death, emigration, or 31 December 2014, whichever came first. Results: We included 169,197 women aged 50–66 from 738 general practices and without previous breast cancer as of 1 January 2006. Women affiliated with a practice referring more women than expected, compared with less, had a lower hazard of breast cancer death (hazard ratio = 0.80; 95% confidence interval = 0.68, 0.95). Negative control associations were near null, suggesting no confounding bias. Conclusions: This quasi-experimental study estimated a continued protective effect of mammography in women where most were presumably asymptomatic. In contrast to conventional observational studies, the use of practice referral ratio as an instrumental variable may avoid bias from uncontrolled confounding.