Functional analysis of carcinoma-associated fibroblasts and response to hormonal therapy in breast cancer

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In postmenopausal breast cancers, CAFs(carcinoma-associated fibroblasts) express aromatase, and locally produce estrogen to activate the estrogen receptor(ER). We established a reporter cell system to detect the ER-activating ability of CAFs under coculture with MCF-7-E10 cells stably transfected with the ERE-GFP gene, and ER activity in breast cancer cells in primary culture by adenovirus-mediated introduction of the ERE-GFP reporter gene. In the cases in which ER-activating abilities of CAF were low, ER-activating abilities correlated with aromatase expression. In these cases, neoadjuvant hormonal therapy with an aromatase inhibitor, exemestane, decreased ER activities in tumor cells and led to a favorable clinical response. Functional analysis of CAF for individual breast cancers might be important to predict the endocrine therapy.