Host microenvironment in breast cancer development: Epithelial-cell–stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland

Mammary epithelial cells comprise the functional component of the normal gland and are the major target for carcinogenesis in mammary cancer. However, the stromal compartment of the normal gland and of tumors plays an important role in directing proliferative and functional changes in the epithelium. In vivo and in vitro studies of the murine mammary gland have provided insights into novel stroma-dependent mechanisms by which estrogen and progesterone action in the epithelium can be modulated by hepatocyte growth factor (HGF) and the extracellular matrix proteins, collagen type I, fibronectin and laminin. In vitro and in vivo studies of estrogen receptor positive, estrogen-responsive human breast cancer cells have also demonstrated that estrogen responsiveness of tumor cells can also be modulated by extracellular matrix proteins, collagen type I and laminin

Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study

BACKGROUND: While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention. METHODS: We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol. RESULTS: No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little evidence of an inverse association for isoflavones, lignans, or coumestrol. CONCLUSIONS: This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance

Absence of interference of serum IgGs from patients with breast cancer and thyroid autoimmunity on the function of human iodide symporter gene stably transfected in CHO cells

The cause of the association between breast cancer (BC) and thyroid autoimmunity is still unknown. Na+/I- symporter (NIS) is highly expressed in BC cells, and previous studies demonstrated that iodine content in BC is lower than in remote normal breast tissue, suggesting a disorder of iodide uptake in BC. In this study, we evaluated the presence of putative serum autoantibodies able to block the function of NIS in BC patients with thyroid autoimmunity. IgGs were obtained from: a) 11 patients with BC and high antithyroglobulin (TgAb) and antithyroperoxidase (TPOAb) autoantibodies serum concentration; b) 34 patients with Hashimoto's thyroiditis (HT) (1 was euthyroid, 4 had subclinical hypothyroidism and 29 were overtly hypothyroid); c) 15 control subjects. The biological activity of NIS was studied using a chinese hamster ovary (CHO) cell line stably expressing NIS (NIS-CHO). The course of iodide accumulation in NIS-CHO was studied after addition of Na125 I in culture medium. The accumulation of iodide linearly increased between 2 and 10 min, reaching a plateau at 45 min. The preincubation of NIS-CHO with IgGs purified from sera of BC with the highest levels of TPOAb and TgAb caused an inhibition of iodine uptake of no more than 5%. Similar results were obtained using IgGs purified from patients with HT and control subjects. Our data showed no interference of autoantibodies on iodine uptake in patients with BC and thyroid autoimmunity and the very low percentage of inhibition of iodine uptake cannot explain the lower content of iodine in BC tissue