Anti-oestrogens such as tamoxifen, decrease the risk of breast cancer but are unsuitable for prevention because of their side-effects. Diet modifications may be a breast cancer prevention strategy. Here, we investigated if a diet addition of flaxseed, which can be converted to the phytoestrogen enterolactone by the gut microbiota, exhibited similar effects as tamoxifen on normal human breast tissue in vivo, with special emphasis on inflammatory mediators implicated in cancer progression.
A total of 28 postmenopausal women were included. Thirteen women added 25 g of ground flaxseed per day and 15 were treated with tamoxifen as an adjuvant for early breast cancer for 6 weeks. Microdialysis of normal breast tissue and, as a control, in subcutaneous abdominal fat was performed for sampling of extracellular proteins in vivo before and after exposures.
Enterolactone levels increased significantly after flaxseed. IL-1Ra and IL-1Ra/IL-1β ratio in the breast increased in a similar fashion after the two different treatments. Flaxseed also increased breast specific levels of IL-1RT2, IL-18 and sST2 and an overall increase of MMP-9. These changes correlated significantly with enterolactone levels. Tamoxifen decreased breast tissue levels of IL-8 and IL-18. None of the treatments induced any changes of IL-1β, IL-1RT1, IL-18BP, IL-33, IL-6, IL-6RA, MMP-1, MMP-2 and MMP-3.
We conclude that dietary flaxseed and tamoxifen exert both similar and different effects, as listed above, on normal breast tissue in vivo and that a relatively modest diet change can induce significant effects on the breast microenvironment.
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The authors would like to thank RN Ann-Christine N Andersson at Linköping University Hospital for providing excellent assistance in recruiting the subjects.
This work was supported by grants to CD from the Swedish Cancer Society (2015/309), the Swedish Research Council (2013–2457), and ALF of Linköping University Hospital.
All authors collaborated on the study conception, study design, and data interpretation. CD and GL recruited the patients. CD performed all microdialysis experiments. AA and GL carried out sample preparation and Luminex and EIA analyses. All authors performed data analysis and drafted the manuscript. All authors read and approved the final version of the manuscript.
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Lindahl, G., Abrahamsson, A. & Dabrosin, C. Dietary flaxseed and tamoxifen affect the inflammatory microenvironment in vivo in normal human breast tissue of postmenopausal women. Eur J Clin Nutr 73, 1250–1259 (2019). https://doi.org/10.1038/s41430-019-0396-y