The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review

Background The tumor microenvironment (TME), particularly the extracellular matrix (ECM), plays a crucial role in regulating breast cancer progression. Among ECM components, collagen type I-accounting for over 90% of fibrillar collagen in the human body-is the primary structural component of the tumor ECM. It critically modulates tumor cell behavior, influencing migration, invasion, and therapy resistance. The structural organization of collagen type I fibers can significantly impact clinical outcomes. Methods This systematic review aimed to assess the association between tumor-stromal collagen type I characteristics and clinical outcomes in breast cancer. A comprehensive search strategy identified studies from major databases, which were appraised using quality assessment tools. Data on collagen quantity, morphology, alignment, and organization were extracted and analyzed to explore their relationship with survival, metastasis, therapy resistance, and clinical characteristics of breast cancer. Results Our analysis revealed that increased collagen density-particularly with an organized/aligned fiber orientation-was strongly associated with poor prognosis. Specifically, increased intratumoral collagen quantity was linked to reduced overall survival (HR = 7.84, p = 0.031). Stage III tumors exhibiting elevated collagen uniformity showed higher metastasis rates (p = 0.004), and HER2(+) tumors with high collagen content correlated with resistance to HER2-targeted therapies (p < 0.05). Furthermore, higher collagen curviness was associated with better outcomes, including a reduced recurrence risk (HR = 0.77, p < 0.001). Subtype-specific trends emerged as ER/PR-negative tumors more frequently exhibited a perpendicular collagen arrangement (p = 0.02), whereas ER/PR-positive tumors showed elevated COL1A1 expression (p < 0.0001). Despite these patterns, the heterogeneity of study methodologies and the complexity of the tumor microenvironment highlight the need for unified frameworks to advance clinical translation. Conclusions This review highlights the prognostic significance of tumor-stromal collagen characteristics in breast cancer, suggesting that future research should focus on the molecular mechanisms underlying collagen remodeling and its potential as a cancer biomarker and therapeutic target.