Abstract

BackgroundMammographic density is a known risk factor for breast cancer, but the underlying pathologic characteristics are not well understood. The current analysis investigated the expression of several markers of interest, e.g., inflammation and growth, with mammographic density (MD) in normal and malignant breast tissue specimens from 279 women of the Multiethnic Cohort (MEC).MethodsBreast cancer cases, recruited from a nested case-control study within the MEC, provided mammograms for density evaluation. Protein expression (COX-2, TNF-α, TGF-β, IGF-1R, IGFBP-2, and vimentin) was assessed by immunohistochemical detection. Linear regression was applied to evaluate the relation between marker expression and percent density and to compute adjusted means with 95% confidence intervals (CI) by marker status while adjusting for confounders.ResultsDue to missing cores and tissue, normal tissue could only be evaluated for COX-2 and vimentin. No significant associations with mammographic density were detected for all markers analyzed. For inflammatory markers (TNF-α, COX-2, and TGF-β) in tumor tissue, MD were non-significantly higher with stronger expression but the differences were very small. For example, the mean MD values for no, weak, and strong TNF-α expression were 35% (95% CI 24–47%), 39% (95% CI 29–48%), and 38% (95% CI 27–50%). In a posthoc analysis among postmenopausal women only, the difference across categories of TNF-α expression increased to 25% (95% CI 12–39%), 35% (95% CI 23–48%), and 35% (95% CI 20–49%).ConclusionsThe current analysis offers little support for an involvement of immunohistochemical markers representing inflammatory and growth factor pathways as predictors of breast density.

Highlights

  • Mammographic density is a known risk factor for breast cancer, but the underlying pathologic characteristics are not well understood

  • Other markers involved in cellular proliferation, such as members of the insulin-like growth factor (IGF) protein family, and in structural and physiological processes of the breast, including vimentin and STAT3, have been implicated in the pathogenesis of cancer

  • Elevated circulating levels of IGF-1/IGFBP-3 and IGF-1R in triple-negative breast cancer are associated with worse survival [8, 9], while IGFBP-2 has been associated with better survival [10]

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Summary

Methods

Breast cancer cases, recruited from a nested case-control study within the MEC, provided mammograms for density evaluation. Protein expression (COX-2, TNF-α, TGF-β, IGF-1R, IGFBP-2, and vimentin) was assessed by immunohistochemical detection. Linear regression was applied to evaluate the relation between marker expression and percent density and to compute adjusted means with 95% confidence intervals (CI) by marker status while adjusting for confounders

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