Stromal cells establish the microenvironment based on interaction with tumor cells, which is essential for cancer growth, invasion and metastasis. Fibroblasts are the primary component of stroma, and carcinoma-associated fibroblasts (CAFs) demonstrate tumor-promoting activities compared with normal counterparts. In breast cancers, stromal fibroblasts adjacent to the tumor express aromatase, a key enzyme in the synthesis of estrogen, resulting in in situ estrogen production, and aromatase is a primary target of endocrine therapy. Thus, stromal fibroblasts demonstrate multiple functions in the genesis and progression of breast cancers. In this paper, we discuss the importance of tumor-stromal crosstalk in breast cancers, and describe our system to predict the efficacy of endocrine therapy and to analyze estrogen signals in individual breast cancers.