Linköping University, Division of Oncology, SE-581 85 Linköping, Sweden.
J Clin Endocrinol Metab. 2012 Nov;97(11):E2044-54. doi: 10.1210/jc.2012-2288. Epub 2012 Aug 28.
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-1α and IL-1β.
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-1β 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-1β in breast cancers of women strongly suggests IL-1 as a potential therapeutic target in breast cancer treatment and prevention.
性激素暴露通过不明机制增加乳腺癌的风险。饮食改变可能是一种乳腺癌预防策略。促炎细胞因子家族的白细胞介素-1（IL-1）参与癌症的进展。IL-1Ra 是促炎的 IL-1α 和 IL-1β 的内源性抑制剂。
本研究旨在阐明雌激素、他莫昔芬和/或饮食改变是否改变了正常人类乳腺组织中的 IL-1 水平。
在各种激素暴露、他莫昔芬治疗和饮食改变以及女性乳腺癌手术前，对健康女性进行微透析。对乳房缩小成形术的乳房组织活检进行培养。
我们显示雌激素与乳腺组织和腹部皮下脂肪中 IL-1β 的体内水平呈显著正相关，而 IL-1Ra 与乳腺组织中的雌激素呈显著负相关。他莫昔芬或每天额外摄入 25 克亚麻籽会导致乳腺中 IL-1Ra 的水平显著升高。这些结果在乳房活检的离体培养中得到了证实。活检的免疫组织化学未显示 IL-1s 的细胞含量有任何变化，这表明主要是分泌水平受到影响。与正常相邻乳腺组织相比，乳腺癌患者的肿瘤内 IL-1β 水平显著升高。
IL-1 可能在体内受雌激素的控制，抗雌激素治疗和饮食改变可能会减弱其作用。女性乳腺癌中 IL-1β 的增加强烈提示 IL-1 可能成为乳腺癌治疗和预防的潜在治疗靶点。
