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Abstract 2705: Differential stromal macrophagic profiles precede ER+ and ER- breast carcinogenesis

Background: Macrophages are well-established components of the inflammatory repertoire in breast cancer (BC) progression. The role of macrophages in early breast carcinogenesis is less understood. Macrophages adopt microenvironment-driven pro- or anti-inflammatory phenotypes. We evaluated macrophagic subsets in benign breast stroma to evaluate their association with future or concurrent BC. Methods: With institutional approval, FFPE tissues were identified from age-matched subjects, [with index benign breast biopsies and (a subset) interval-matched second benign tissues taken at the time of one of three events: ER+ BC, ER- BC or no cancer event (Controls) (index N=32, 26 and 30 respectively)]. Tissues were immunostained (CD68 or CD163) and stromal CD68+ and CD163+ macrophagic cell densities (MCD) (cells/mm2 stromal fibroadipose area) were digitally quantified. Statistical analysis was performed using Wilcoxon signed-rank tests for univariate analysis and conditional logistic regression models to adjust for BMI. Results: In the index age-matched biopsies (median age 54y), within subjects in all groups, the median CD163+ MCD (54.5; range: 13.9-371.3) was significantly higher than CD68+ MCD (19.6, range: 3.5-78.5) but the two were strongly correlated (r = 0.76); neither correlated with BMI (r Conclusion: Benign breast tissues have higher stromal CD163+ MCD than CD68+ MCD irrespective of future BC events and independent of BMI. However, between index and second biopsies/excisions, the stromal CD68+ MCD differentially increased in all groups, lowering CD163+:CD68+ MCD ratios, and likely shifting pro- and anti-inflammatory stromal macrophage functionality. Across groups, ER- BC index biopsies had significantly lower stromal MCD of both types compared to ER+ BC, and were the only group to increase stromal CD163+ MCD between index biopsy and cancer event. These data suggest that ER+ and ER- BC may have different pre-carcinogenic stromal inflammatory microenvironments. Citation Format: Jodi M. Carter, Ethan P. Heinzen, Tanya L. Hoskin, Stacey J. Winham, Derek C. Radisky, Daniel W. Visscher, Amy C. Degnim. Differential stromal macrophagic profiles precede ER+ and ER- breast carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2705.