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

Abstract 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 o...

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Main Authors: Samane Heydari, Fatemeh Tajik, Sadegh Safaei, Fereshteh Kamani, Babak Karami, Shima Dorafshan, Zahra Madjd, Roya Ghods
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Breast Cancer Research
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Online Access:https://doi.org/10.1186/s13058-025-02017-6
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author Samane Heydari
Fatemeh Tajik
Sadegh Safaei
Fereshteh Kamani
Babak Karami
Shima Dorafshan
Zahra Madjd
Roya Ghods
author_facet Samane Heydari
Fatemeh Tajik
Sadegh Safaei
Fereshteh Kamani
Babak Karami
Shima Dorafshan
Zahra Madjd
Roya Ghods
author_sort Samane Heydari
collection DOAJ
description Abstract 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.
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spelling doaj-art-e5887a6e87da43a38718161cff2cec842025-08-20T03:53:16ZengBMCBreast Cancer Research1465-542X2025-05-0127112410.1186/s13058-025-02017-6The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic reviewSamane Heydari0Fatemeh Tajik1Sadegh Safaei2Fereshteh Kamani3Babak Karami4Shima Dorafshan5Zahra Madjd6Roya Ghods7Oncopathology Research Center, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesDepartment of General Surgery, Shahid Beheshti University of Medical SciencesDepartment of Physics, Sharif University of TechnologyOncopathology Research Center, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesAbstract 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.https://doi.org/10.1186/s13058-025-02017-6Collagen type IBreast cancerExtracellular matrixTumor microenvironmentPrognostic markerSystematic review
spellingShingle Samane Heydari
Fatemeh Tajik
Sadegh Safaei
Fereshteh Kamani
Babak Karami
Shima Dorafshan
Zahra Madjd
Roya Ghods
The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review
Breast Cancer Research
Collagen type I
Breast cancer
Extracellular matrix
Tumor microenvironment
Prognostic marker
Systematic review
title The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review
title_full The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review
title_fullStr The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review
title_full_unstemmed The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review
title_short The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review
title_sort association between tumor stromal collagen features and the clinical outcomes of patients with breast cancer a systematic review
topic Collagen type I
Breast cancer
Extracellular matrix
Tumor microenvironment
Prognostic marker
Systematic review
url https://doi.org/10.1186/s13058-025-02017-6
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