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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2020

Open Access 01-02-2020 | Obesity | Preclinical study

Tumor microenvironment and breast cancer survival: combined effects of breast fat, M2 macrophages and hyaluronan create a dismal prognosis

Authors: Satu Tiainen, Amro Masarwah, Sanna Oikari, Kirsi Rilla, Kirsi Hämäläinen, Mazen Sudah, Anna Sutela, Ritva Vanninen, Juho Ikonen, Raija Tammi, Markku Tammi, Päivi Auvinen

Published in: Breast Cancer Research and Treatment | Issue 3/2020

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Abstract

Purpose

Tumor microenvironment, including inflammatory cells, adipocytes and extracellular matrix constituents such as hyaluronan (HA), impacts on cancer progression. Systemic metabolism also influences tumor growth e.g. obesity and type 2 diabetes (T2D) are risk factors for breast cancer. Here, in 262 breast cancer cases, we explored the combined impacts on survival of M2-like tumor associated macrophages (TAMs), the abundance of breast fat visualized as low density in mammograms, and tumor HA, and their associations with T2D.

Methods

Mammographic densities were assessed visually from the diagnostic images and dichotomized into very low density (VLD, density ≤ 10%, “fatty breast”) and mixed density (MID, density > 10%). The amounts of TAMs (CD163+ and CD68+) and tumor HA were determined by immunohistochemistry. The data of T2D was collected from the patient records. Statistical differences between the parameters were calculated with Chi square or Mann–Whitney test and survival analyses with Cox’s model.

Results

A combination of fatty breasts (VLD), abundance of M2-like TAMs (CD163+) and tumor HA associated with poor survival, as survival was 88–89% in the absence of these factors but only 40–47% when all three factors were present (p < 0.001). Also, an association between T2D and fatty breasts was found (p < 0.01). Furthermore, tumors in fatty breasts contained more frequently high levels of M2-like TAMs than tumors in MID breasts (p = 0.01).

Conclusions

Our results demonstrate a dramatic effect of the tumor microenvironment on breast cancer progression. We hypothesize that T2D as well as obesity increase the fat content of the breasts, subsequently enhancing local pro-tumoral inflammation.
Appendix
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Metadata
Title
Tumor microenvironment and breast cancer survival: combined effects of breast fat, M2 macrophages and hyaluronan create a dismal prognosis
Authors
Satu Tiainen
Amro Masarwah
Sanna Oikari
Kirsi Rilla
Kirsi Hämäläinen
Mazen Sudah
Anna Sutela
Ritva Vanninen
Juho Ikonen
Raija Tammi
Markku Tammi
Päivi Auvinen
Publication date
01-02-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05491-7

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