Estradiol, Tamoxifen, and Flaxseed Alter IL – 1β and IL-1Ra Levels in Normal Human Breast Tissue in Vivo.

January 1, 2012 Human Health and Nutrition Data 0 Comments

Estradiol, Tamoxifen, and Flaxseed Alter IL – 1β and IL-1Ra Levels in Normal Human Breast Tissue in Vivo.

Year: 2012
Authors: Abrahamsson, A. Morad, V. Saarinen, N.M. Dabrosin, C.
Publication Name: J Clin Endocrinol Metab.
Publication Details: DOI.10.1210/jc.2012-2288


Sex steroid exposure increases the risk of breast cancer by unclear mechanisms. Diet modifications may be one breast cancer prevention strategy. The proinflammatory cytokine family of IL 1 is implicated in cancer progression. IL 1Ra is an endogenous inhibitor of the proinflammatory IL 1alpha and IL 1beta. The objective of this study was to elucidate whether estrogen, tamoxifen, and/or diet modification altered IL 1 levels in normal human breast tissue. Microdialysis was performed in healthy women under various hormone exposures, tamoxifen therapy, and diet modifications and in breast cancers of women before surgery. Breast tissue biopsies from reduction mammoplasties were cultured. We show a significant positive correlation between estradiol and in vivo levels of IL 1beta in breast tissue and abdominal sc fat, whereas IL 1Ra exhibited a significant negative correlation with estradiol in breast tissue. Tamoxifen or a dietary addition of 25 g flaxseed per day resulted in significantly increased levels of IL 1Ra in the breast. These results were confirmed in ex vivo culture of breast biopsies. Immunohistochemistry of the biopsies did not reveal any changes in cellular content of the IL 1s, suggesting that mainly the secreted levels were affected. In breast cancer patients, intratumoral levels of IL 1β were significantly higher compared with normal adjacent breast tissue. IL 1 may be under the control of estrogen in vivo and may be attenuated by antiestrogen therapy and diet modifications. The increased IL 1beta in breast cancers of women strongly suggests IL 1 as a potential therapeutic target in breast cancer treatment and prevention. (Authors abstract)
The results show that estradiol increased the levels of IL 1betaand decreased IL 1Ra, suggesting that hormone exposure induced a proinflammatory environment in the breast. In  premenopausal women, the proinflammatory profile of IL 1 could be counteracted by a diet addition of 25 g of ground flaxseed for one menstrual cycle. IL 1Ra increased significantly in breast tissue, whereas IL 1beta remained at similar levels as before the addition of flaxseed. The IL 1Ra levels in breast tissue increased by over 50 percent after flaxseed ingestion, which was in the same range and even slightly higher than in women after tamoxifen therapy where IL 1Ra increased by approximately 40 percent. Immunohistochemistry of breast tissue biopsies did not reveal any changes with either treatment, suggesting that mainly the secreted levels of IL 1 were affected. In breast cancer tumors, IL 1 exhibited a proinflammatory pattern with more than three times higher IL 1alpha levels, compared with adjacent normal breast tissue with IL 1Ra levels not significantly higher in tumor tissue than the adjacent normal breast. The antiestrogen tamoxifen reduces the incidence of breast cancer by more than 40 percent but may induce severe side effects such as endometrial cancer and thromboembolism. The researchers have shown in experimental breast cancer models as well as in normal breast tissue that a diet of flaxseed affects several angiogenesis regulators toward angiogenesis inhibition. This study supports an additional mechanism of action of flaxseed by the shift of IL 1 levels into an anti-inflammatory state. Flaxseed has previously been shown to exhibit powerful biological activity in breast cancer patients where a daily addition of 25 g of flaxseed for 30 d attenuated several biological tumor markers. In conclusion, the data revealed an estrogen-dependent increase of IL 1alpha and a decrease of IL 1Ra in normal human breast tissue in vivo. The levels of IL 1Ra in normal human breast tissue in vivo increased significantly both by a diet of flaxseed and by tamoxifen therapy. Diet modifications may exert potent biological activities in breast tissue, which merit further mechanistic studies to elucidate safety and effects as breast cancer prevention strategies. In breast cancers of women before surgery, a proinflammatory environment was detected by increased levels of IL 1alpha and unaltered levels of IL 1Ra, suggesting blockade of IL 1 as a therapeutic option useful to explore in the clinic. (Editors comments)

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