{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:39:22Z","timestamp":1789202362902,"version":"build-2803163510"},"reference-count":95,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Breast cancer is a biologically complex malignancy whose high prevalence and therapeutic resistance represent a continuous challenge for global health. The Tumor Microenvironment (TME) is a crucial component in disease progression, and the Extracellular Matrix (ECM), particularly its 3D collagen architecture, is recognized for mediating interactions that influence invasion, metastasis, and pharmacological response. This review aims to critically synthesize recent evidence to elucidate the multifaceted role of collagen in the progression and modulation of therapeutic response in breast adenocarcinoma. Methods: A comprehensive literature review was conducted, analyzing studies addressing specific collagen subtypes, ECM stiffening (fibrosis), biomechanical signaling, and their impact on drug transport kinetics and immunomodulatory effects. Results: The results demonstrate that structural alterations of collagen not only orchestrate a pro-tumoral microenvironment, fostering aggressive phenotypes and immune evasion, but also create a physical barrier that compromises drug delivery efficiency and promotes metastatic dissemination. The synthesis of the data reinforces collagen as a potent prognostic biomarker and a promising therapeutic target for overcoming stroma-mediated resistance. Conclusions: Targeting the collagen-rich stroma and its 3D network is a critical frontier for therapeutic innovation. Developing adjuvant strategies to modulate the ECM has the potential to enhance clinical outcomes and optimize the distribution of antineoplastic agents, especially in patients with high degrees of tumor fibrosis.<\/jats:p>","DOI":"10.3390\/pharmaceutics18030340","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T08:43:31Z","timestamp":1773132211000},"page":"340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The 3D Collagen Network as a Determinant of Tumor Progression and Drug Delivery Efficiency in Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Mariana","family":"Hirata","sequence":"first","affiliation":[{"name":"School of Medicine, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogerio Padovan","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Interdisciplinary Pos Graduate Program in Structural and Functional Interactions in Rehabilitation, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eduarda Teixeira Pereira C\u00e2ndido","family":"da Silva","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geovanna de Castro","family":"Feitosa","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio S\u00e9rgio Galina","family":"Spilla","sequence":"additional","affiliation":[{"name":"Department of Human Morphophysiology, School of Medicine, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domingos Donizeti","family":"Roque","sequence":"additional","affiliation":[{"name":"Department of Human Morphophysiology, School of Medicine, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisete Horn Belon","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Theoretical Bases of Mental Health, School of Medicine, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virg\u00ednia Maria Cavallari Strozze","family":"Catharin","sequence":"additional","affiliation":[{"name":"Interdisciplinary Pos Graduate Program in Structural and Functional Interactions in Rehabilitation, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Department of Biochemistry and Pharmacology, School of Medicine, University of Mar\u00edlia (UNIMAR) Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Cavallari Strozze","family":"Catharin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, University of Mar\u00edlia (UNIMAR) Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila Maria Guissoni","family":"Campos","sequence":"additional","affiliation":[{"name":"Interdisciplinary 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Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Department of Prosthodontics, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana da Silva Soares","family":"de Souza","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricelma da Silva Soares","family":"de Souza","sequence":"additional","affiliation":[{"name":"Interdisciplinary Pos Graduate Program in Structural and Functional Interactions in Rehabilitation, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Department of Biochemistry and Pharmacology, School of 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose Eli Grassi","family":"Rici","sequence":"additional","affiliation":[{"name":"Interdisciplinary Pos Graduate Program in Structural and Functional Interactions in Rehabilitation, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Graduate Program in Anatomy of Domestic and Wild Animals, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-270, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2858-4717","authenticated-orcid":false,"given":"Karina Torres","family":"Pomini","sequence":"additional","affiliation":[{"name":"Interdisciplinary Pos Graduate Program in Structural and Functional Interactions in Rehabilitation, University of Mar\u00edlia (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Department of Human 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