A comparative analysis of risk factor associations with interval and screen-detected breast cancers: A large UK prospective study

The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen-detected cancers. However, the extent to which associations of other established breast cancer risk factors differ by mode of detection is unclear. We investigated associations of a wide range of risk factors using data from a large UK cohort with linkage to the National Health Service Breast Screening Programme, cancer registration, and other health records. We used Cox regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for associations between risk factors and breast cancer risk. A total of 9421 screen-detected and 5166 interval cancers were diagnosed in 517,555 women who were followed for an average of 9.72 years. We observed the following differences in risk factor associations by mode of detection: greater body mass index (BMI) was associated with a smaller increased risk of interval (RR per 5 unit increase 1.07, 95% CI 1.03–1.11) than screen-detected cancer (RR 1.27, 1.23–1.30); having a first-degree family history was associated with a greater increased risk of interval (RR 1.81, 1.68–1.95) than screen-detected cancer (RR 1.52, 1.43–1.61); and having had previous breast surgery was associated with a greater increased risk of interval (RR 1.85, 1.72–1.99) than screen-detected cancer (RR 1.34, 1.26–1.42). As these differences in associations were relatively unchanged after adjustment for tumour grade, and are in line with the effects of these factors on mammographic density, they are likely to reflect the effects of these risk factors on screening sensitivity.