Regulation of Stromal Cells by Sex Steroid Hormones in the Breast Cancer Microenvironment.

Breast cancer is a prevalent hormone-dependent malignancy, and estrogens/estrogen receptor (ER) signaling are pivotal therapeutic targets in ER-positive breast cancers, where endocrine therapy has significantly improved treatment efficacy. However, the emergence of both de novo and acquired resistance to these therapies continues to pose challenges. Additionally, androgens are produced locally in breast carcinoma tissues by androgen-producing enzymes, and the androgen receptor (AR) is commonly expressed in breast cancer cells. Intratumoral androgens play a significant role in breast cancer progression and are closely linked to resistance to endocrine treatments. The tumor microenvironment, consisting of tumor cells, immune cells, fibroblasts, extracellular matrix, and blood vessels, is crucial for tumor progression. Stromal cells influence tumor progression through direct interactions with cancer cells, the secretion of soluble factors, and modulation of tumor immunity. Estrogen and androgen signaling in breast cancer cells affects the tumor microenvironment, and the expression of hormone receptors correlates with the diversity of the stromal cell profile. Notably, various stromal cells also express ER or AR, which impacts breast cancer development. This review describes how sex steroid hormones, particularly estrogens and androgens, affect stromal cells in the breast cancer microenvironment. We summarize recent findings focusing on the effects of ER/AR signaling in breast cancer cells on stromal cells, as well as the direct effects of ER/AR signaling in stromal cells.