Stromal COL11A1: Mechanisms of Stroma-Driven Multidrug Resistance in Breast Cancer and Biomarker Potential

Background/Objectives: Therapeutic resistance remains a major obstacle in breast cancer management, particularly among estrogen receptor-positive (ERα⁺) tumors that initially respond to endocrine therapy such as tamoxifen. Type XI collagen (COL11A1), a minor fibrillar collagen secreted by cancer-associated fibroblasts, has recently emerged as a stromal biomarker linked to tumor progression, immune modulation, and poor prognosis in several solid malignancies. Methods: We conducted a narrative review of the literature indexed in PubMed, Scopus, and Web of Science between 2011 and 2025, including original research, reviews, and clinical studies addressing COL11A1 expression and function in breast cancer. Mechanistic studies in other cancer types (ovarian, pancreatic, lung) were also evaluated when relevant to breast cancer biology. Results: Across multiple cancer types, COL11A1 overexpression correlates with stromal remodeling, epithelial-mesenchymal transition, and resistance to both hormone therapy and chemotherapy. In breast cancer, emerging data suggest a potential prognostic role and possible involvement in shaping the immune microenvironment. Nevertheless, most evidence derives from retrospective or preclinical studies, and clinical validation remains limited. Conclusions: COL11A1 represents a promising, though still exploratory, biomarker of therapeutic resistance and immune modulation in breast cancer. Future prospective and subtype-specific studies are needed to clarify its diagnostic and therapeutic value and to determine whether its inclusion in immunohistochemical panels could enhance patient stratification and guide personalized treatment.