Introduction: Percent mammographic density (PMD) is associated with an increased risk of interval breast cancer in screening programs, as are younger age, pre-menopausal status, lower body mass index and hormone therapy. These factors are also associated with variations in PMD. We have examined whether these variables influence the relative frequency of interval and screen-detected breast cancer, independently or through their associations with PMD. We also examined the association of tumor size with PMD and dense and non-dense areas in screen-detected and interval breast cancers.
Methods: We used data from three case-control studies nested in screened populations. Interval breast cancer was defined as invasive breast cancer detected within 12 months of a negative mammogram. We used a computer-assisted method of measuring the dense and total areas of breast tissue in the first (baseline) mammogram taken at entry to screening programs and calculated the non-dense area and PMD. We compared these mammographic features, and other risk factors at baseline, in women with screen-detected (n = 718) and interval breast cancer (n = 125).
Results: In multi-variable analysis, the baseline characteristics of younger age, greater dense area and smaller non-dense mammographic area were significantly associated with interval breast cancer compared to screen-detected breast cancer. Compared to screen-detected breast cancers, interval cancers had a larger maximum tumor diameter within each mammographic measure.
Conclusions: Age and the dense and non-dense areas in the baseline mammogram were independently associated with interval breast cancers in screening programs. These results suggest that decreased detection of cancers caused by the area of dense tissue, and more rapid growth associated with a smaller non-dense area, may both contribute to risk of interval breast cancer. Tailoring screening to individual mammographic characteristics at baseline may reduce the number of interval cancers.