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Stromal type I collagen in breast cancer: correlation to prognostic biomarkers and prediction of chemotherapy response
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.ORCID iD: 0000-0003-2624-4671
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.ORCID iD: 0000-0002-8601-0159
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2024 (English)In: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666Article in journal (Refereed) In press
Abstract [en]

Introduction: Fibrillar collagens accumulate in the breast cancer stroma and appear as poorly defined spiculated masses in mammography imaging. The prognostic value of tissue type I collagen remains elusive in treatment-naïve and chemotherapy-treated breast cancer patients. Here, type I collagen mRNA and protein expression were analysed in 2 large independent breast cancer cohorts. Levels were related to clinicopathological parameters, prognostic biomarkers, and outcome.

Method: COL1A1 mRNA expression was analysed in 2509 patients with breast cancer obtained from the cBioPortal database. Type I collagen protein expression was studied by immunohistochemistry in 1395 women diagnosed with early invasive breast cancer.

Results: Low COL1A1 mRNA and protein levels correlated with poor prognosis features, such as hormone receptor negativity, high histological grade, triple-negative subtype, node positivity, and tumour size. In unadjusted analysis, high stromal type I collagen protein expression was associated with improved overall survival (OS) (HR = 0.78, 95% CI = 0.61-0.99, p = .043) and trended towards improved breast cancer–specific survival (BCSS) (HR = 0.65, 95% CI = 0.42-1.01, P = 0.053), although these findings were lost after adjustment for other clinical variables. In unadjusted analysis, high expression of type I collagen was associated with better OS (HR = 0.70, 95% CI = 0.55-0.90, P = .006) and BCSS (HR = 0.55, 95% CI = 0.34-0.88, P = .014) among patients not receiving chemotherapy. Strikingly, the opposite was observed among patients receiving chemotherapy. There, high expression of type I collagen was instead associated with worse OS (HR = 1.83, 95% CI = 0.65-5.14, P = .25) and BCSS (HR = 1.72, 95% CI = 0.54-5.50, P = .357).

Conclusion: Low stromal type I collagen mRNA and protein expression are associated with unfavourable tumour characteristics in breast cancer. Stromal type I collagen might predict chemotherapy response.

Place, publisher, year, edition, pages
Elsevier, 2024.
Keywords [en]
Breast cancer, Chemotherapy response, Extracellular matrix, Tumour microenvironment, Type I collagen
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-223260DOI: 10.1016/j.clbc.2024.02.015PubMedID: 38485557Scopus ID: 2-s2.0-85187983725OAI: oai:DiVA.org:umu-223260DiVA, id: diva2:1852394
Funder
The Breast Cancer FoundationRegion Västerbotten, RV-866131Region Västerbotten, RV-932421Region Västerbotten, RV-764621Visare Norr, VISARENORR931408Visare Norr, VISARENORR750491Percy Falks stiftelse för forskning beträffande prostatacancer och bröstcancerAvailable from: 2024-04-18 Created: 2024-04-18 Last updated: 2024-04-18

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Jansson, MalinLindberg, JessicaRask, GunillaSvensson, JohanBilling, OlaNazemroaya, AnooshehBerglund, AnetteSund, Malin

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