| Summary: | Abstract Background We evaluated the association between volumetric breast density (BD) and risk of advanced cancers after a negative screening episode. Methods A cohort of 16,752 women aged 49–54 years at their first screening mammography in the Florence screening programme was followed for breast cancer (BC) incidence until the second screening round. Volumetric BD was measured using fully automated software. The cumulative incidence of advanced cancer after a negative screening episode (including stage II or more severe cancer during the screening interval - on average 28 months - and at the subsequent round) was calculated separately for Volpara density grade (VDG) categories. Results BC incidence gradually increased with the increas in BD: 3.7‰, 5.1‰, 5.4‰ and 9.1‰ in the VDG categories 1–4, respectively (p trend < 0.001). The risk of advanced cancers after a negative screening episode was 1.0‰, 1.3‰, 1.1‰, and 4.2‰ (p trend = 0.003). The highest BD category, compared with the other three together, has double the invasive BC risk (RR = 2.0; 95% CI 1.5–2.8) and almost fourfold risk of advanced cancer (RR = 3.8; 95% CI 1.8–8.0). Conclusion BD has a strong impact on the risk of advanced cancers after a negative screening episode, the best early surrogate of BC mortality. Therefore, our results suggest that screening effectiveness is quite different among BD categories.
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