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Abstract
BackgroundInterval breast cancers are often diagnosed at a more advanced stage than screen-detected cancers. Our aim was to identify features in screening mammograms of the normal breast that would differentiate between future interval cancers and screen-detected cancers, and to understand how each feature affects tumor detectability.MethodsFrom a population-based cohort of invasive breast cancer cases in Stockholm-Gotland, Sweden, diagnosed from 2001 to 2008, we analyzed the contralateral mammogram at the preceding negative screening of 394 interval cancer cases and 1009 screen-detected cancers. We examined 32 different image features in digitized film mammograms, based on three alternative dense area identification methods, by a set of logistic regression models adjusted for percent density with interval cancer versus screen-detected cancer as the outcome. Features were forward-selected into a multiple logistic regression model adjusted for mammographic percent density, age, BMI and use of hormone replacement therapy. The associations of the identified features were assessed also in a sample from an independent cohort.ResultsTwo image features, ‘skewness of the intensity gradient’ and ‘eccentricity’, were associated with the risk of interval compared with screen-detected cancer. For the first feature, the per-standard deviation odds ratios were 1.32 (95 % CI: 1.12 to 1.56) and 1.21 (95 % CI: 1.04 to 1.41) in the primary and validation cohort respectively. For the second feature, they were 1.20 (95 % CI: 1.04 to 1.39) and 1.17 (95%CI: 0.98 to 1.39) respectively. The first feature was associated with the tumor size at screen detection, while the second feature was associated with the tumor size at interval detection.ConclusionsWe identified two novel mammographic features in screening mammograms of the normal breast that differentiated between future interval cancers and screen-detected cancers. We present a starting point for further research into features beyond percent density that might be relevant for interval cancer, and suggest ways to use this information to improve screening.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0761-x) contains supplementary material, which is available to authorized users.
Highlights
Interval breast cancers are often diagnosed at a more advanced stage than screen-detected cancers
From fitting linear regression models with tumor size as the outcome, separately for screen-detected cancer (SC) and Interval cancer (IC), we found significant evidence that high ‘skewness of the intensity gradient’ of the dense area is associated with an increased tumor size for SCs, but not for ICs (Table 4)
We identified two novel mammographic features in screening mammograms of the normal breast that differentiated between future interval cancers and screendetected cancers
Summary
Interval breast cancers are often diagnosed at a more advanced stage than screen-detected cancers. Our aim was to identify features in screening mammograms of the normal breast that would differentiate between future interval cancers and screen-detected cancers, and to understand how each feature affects tumor detectability. Interval cancer (IC) is a cancer that is diagnosed in the interval between two mammographic screening visits. Several breast cancer screening strategies have been proposed which might decrease the IC incidence, such as increasing the screening frequency [8] or using supplemental imaging [9] in addition to mammography, e.g., magnetic resonance imaging (MRI) or ultrasound. There is a need to more accurately identify women at high risk of interval breast cancer and to understand which strategy would be most adequate for decreasing the risk of interval cancer by earlier screen detection
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