Tumor microenvironment and breast cancer survival: combined effects of breast fat, M2 macrophages and hyaluronan create a dismal prognosis.
Breast Cancer Res Treat
; 179(3): 565-575, 2020 Feb.
Article
en En
| MEDLINE
| ID: mdl-31720917
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Tejido Adiposo
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Microambiente Tumoral
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Densidad de la Mama
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Ácido Hialurónico
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Macrófagos
Tipo de estudio:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Breast Cancer Res Treat
Año:
2020
Tipo del documento:
Article
País de afiliación:
Finlandia