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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2015

01-10-2015 | Epidemiology

The reciprocal association between mammographic breast density, hyaluronan synthesis and patient outcome

Authors: Amro Masarwah, Markku Tammi, Mazen Sudah, Anna Sutela, Sanna Oikari, Veli-Matti Kosma, Raija Tammi, Ritva Vanninen, Päivi Auvinen

Published in: Breast Cancer Research and Treatment | Issue 3/2015

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Abstract

Low mammographic breast density (MBD) and increased hyaluronan (HA) synthesis have been shown to have adverse effects on breast cancer prognosis. We aimed at elucidating the background of risk associated with mammographic characteristics, MBD and HA and its synthesizing isoforms in an attempt to uncover potential underlying biological mechanisms. MBD and mammographic characteristics of 270 patients were classified according to percentile density (very low density VLD, ≤25 %; mixed density MID, >25 %) and the BI-RADS 5th edition lexicon. Breast density and mammographic features were correlated with the localization and expression of HA, CD44, and HAS1-3 isoforms, and their combined effect on patients’ survivals was explored. VLD showed an increased level of HA-positive carcinoma cells and stromal HA, HAS2, and HAS3. Tumors presenting as masses had more HA-positive carcinoma cells and more stromal HAS2 and HAS3. Indistinct margin tumors showed more stromal HA and HAS3. Patients who combined both VLD breasts with either high HA in carcinoma cells or stroma showed a worse prognosis compared to low levels (carcinoma cells 58.0 vs. 80.5 %, p = 0.001; stroma 64.2 vs. 79.6 %, p = 0.017), while no similar HA-related effect was observed in MID breasts. Our findings suggest a strong reciprocal relationship between low MBD and HA expression and synthesis. The expression of both factors simultaneously leads to an especially adverse prognostic effect which might have an impact on treatment decision in the future. Moreover, HA around cancer cells may inhibit chemotherapy agents and antibody treatments from reaching cancer cells.
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Metadata
Title
The reciprocal association between mammographic breast density, hyaluronan synthesis and patient outcome
Authors
Amro Masarwah
Markku Tammi
Mazen Sudah
Anna Sutela
Sanna Oikari
Veli-Matti Kosma
Raija Tammi
Ritva Vanninen
Päivi Auvinen
Publication date
01-10-2015
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-015-3567-0

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