Localized mammographic density is associated with interval cancer and large breast cancer: a nested case-control study

Fredrik Strand, Edward Azavedo, Roxanna Hellgren, Keith Humphreys, Mikael Eriksson, John Shepherd, Per Hall, Kamila Czene, Fredrik Strand, Edward Azavedo, Roxanna Hellgren, Keith Humphreys, Mikael Eriksson, John Shepherd, Per Hall, Kamila Czene

Abstract

Background: High mammographic density is associated with breast cancer and with delayed detection. We have examined whether localized density, at the site of the subsequent cancer, is independently associated with being diagnosed with a large-sized or interval breast cancer.

Methods: Within a prospective cohort of 63,130 women, we examined 891 women who were diagnosed with incident breast cancer. For 386 women, retrospective localized density assessment was possible. The main outcomes were interval cancer vs. screen-detected cancer and large (> 2 cm) vs. small cancer. In negative screening mammograms, overall and localized density were classified reflecting the BI-RADS standard. Density concordance probabilities were estimated through multinomial regression. The associations between localized density and the two outcomes were modeled through logistic regression, adjusted for overall density, age, body mass index, and other characteristics.

Results: The probabilities of concordant localized density were 0.35, 0.60, 0.38, and 0.32 for overall categories "A," "B," "C," and "D." Overall density was associated with large cancer, comparing density category D to A with OR 4.6 (95%CI 1.8-11.6) and with interval cancer OR 31.5 (95%CI 10.9-92) among all women. Localized density was associated with large cancer at diagnosis with OR 11.8 (95%CI 2.7-51.8) among all women and associated with first-year interval cancer with OR 6.4 (0.7 to 58.7) with a significant linear trend p = 0.027.

Conclusions: Overall density often misrepresents localized density at the site where cancer subsequently arises. High localized density is associated with interval cancer and with large cancer. Our findings support the continued effort to develop and examine computer-based measures of localized density for use in personalized breast cancer screening.

Keywords: Breast cancer; Early detection; Mammographic density; Mammography; Screening.

Conflict of interest statement

Ethics approval and consent to participate

The regional ethical review board at Karolinska Institutet, Stockholm, Sweden, granted ethical approval (DNR2009/254-31/4) and all participants gave written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Examples of cases with discordant overall and localized density. DIAGNOSIS denotes the mammogram at the time of diagnosis. PRIOR denotes the mammogram from the prior screening (median time 1.99 years before DIAGNOSIS). DIAGNOSIS was used to localize the tumor (red arrow), while PRIOR was used to assess the overall and localized (red circle) density
Fig. 2
Fig. 2
Distribution across categories of the overall and localized mammographic density of the 386 women with incident breast cancer for which local density assessment was performed. Category A is the least dense, and category D is the most dense. Marker placements within each rectangle carry no meaning; jittered for enhanced visibility. There is a moderate correlation between the two density parameters (r = 0.42). Percentage numbers show the proportion of cases within each overall density category

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