Breast cancer is the most common cancer in women, which incidence has increased in recent
years. It is constituted by very heterogeneous tissue characterized by an abnormal microenvironment regulating
tumor progression and providing evasion from cancer therapies. Breast cancer-associated fibroblasts
(BCAFs) are the main cell type of breast cancer microenvironment and can represent up to 80% of the tumor
mass. In particular, BCAFs induce cancer initiation, proliferation, invasion and metastasis by undergoing
an activation process associated with the secretion of growth factors, cytokines, and paracrine interactions.
Therapy resistance is the main cause of poor therapeutic results or even failure in breast cancer
patients. Despite recent advances in breast cancer management, there is a need for new prognostic markers
and novel agents for targeting key signalling pathways to either improve the efficacy of the current
therapies, or reduce toxicity. In this view, BCAFs represent markers useful to clinical diagnosis, therapy,
and prognosis of breast cancer. This review focuses on the role of BCAFs in cancer, and describes the
processes of endocrine/chemotherapy resistance linked to BCAFs action. Moreover, it points to molecules
and pathways regulating therapy resistance induced by BCAFs. Finally, potential therapeutic strategies
targeting BCAFs and offering new tools in breast cancer therapy are highlighted.