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Recombinant human erythropoietin (rhEPO) is used in breast and ovarian cancer patients to alleviate cancer- and chemotherapy-related anemia. Some clinical trials have reported that rhEPO may adversely impact survival and increase the risk of thrombovascular events in patients with breast cancer but not with ovarian cancer. The latter may potentially benefit the most from rhEPO treatment due to the nephrotoxic and myelosuppresive effects of standard platinum-based chemotherapy used in ovarian cancer disease. However, over the last decade the preclinical data have revealed that EPO is not only the principal growth factor and the hormone which regulates erythropoiesis, but also a cytokine with a pleiotropic activity which also can affect cancer cells. EPO can stimulate survival, ability to form metastases and drug resistance not only in continuous breast- and ovarian cancer cell lines but also in breast cancer stem-like cells. EPO receptor (EPOR) can also be constitutively active in both these cancers and, in breast cancer cells, may act in an interaction with estrogen receptor (ER) and epidermal growth factor receptor-2 (HER-2). EPOR, by an EPO-independent mechanism, promotes proliferation of breast cancer cells in cooperation with estrogen receptor, resulting in decreased effectiveness of tamoxifen treatment. In another interaction, as a result of the molecular antagonism between EPOR and HER2, rhEPO protects breast cancer cells against trastuzumab. Both clinical and preclinical evidence strongly suggest the urgent need to reevaluate the traditional use of rhEPO in the oncology setting.

Recent studies reveal that estrogens act on cells and tissues, not only through two canonical estrogen receptors ERα and ERβ, but also through the receptor coupled with G proteins, named GPER, formerly GPR30, and member of seven transmembrane receptor superfamily. GPER was found to be implicated both in rapid non-genomic estrogen response and in transcriptional regulation. Effects of GPER include activation of MAPK and PI3K signaling pathways, stimulation of adenyl cyclase, and mobilization of calcium ions from intracellular stores, as well as upregulation of genes such as FOS and CTGF. Identification of agonists and antagonists of GPER allowed not only to shed light on the participation of estrogen signaling in the biology and pathobiology of hormone-dependent tissues, but also its importance in the estrogen and antiestrogen therapies. Antiestrogens tamoxifen, raloxifene, or fulvestrant proved,to be agonists of GPER, which undoubtedly is not without significance for the efficacy of the therapy.

Treatment of cancer involves not only appropriate pharmacological or psychological therapy and rehabilitation, but also diet aimed at prevention of the process of cachexia. Postprandial hyperglycemia exerts a significant effect on the growth and proliferation of tumor cells. It promotes formation of a number of metabolic changes in every tissue of the organism. Chronic postprandial hyperglycemia, occurring in type 2 diabetes, enhances all these changes. Although the results of epidemiological studies on the relationship between the overall risk of cancer development, or tumors in different parts of the organism, are heterogeneous, most of them indicate that the risk increases with an increase in glycemic load of the examined population's diets. Researchers also suggest a beneficial effect of limiting the amount of easily assimilable carbohydrate in the diet to stabilize the disease and for better tolerance of chemo or radiation therapy. However, further studies are required.

The review evaluates the role of vitamin D in carcinogenesis. Based on ecological studies, the incidence of many cancers has been shown to be higher in northern countries, suggesting an association with latitude and solar radiation. Vitamin D produced in skin under the influence of sun exposure may play a protective role in the process leading to cancer. Vitamin D deficiency is now recognized as a pandemic, mainly due to lack of knowledge that sun exposure in moderation is the major source of vitamin D for most humans. After vitamin D was discovered to be the necessary element of nourishment to prevent rickets at the beginning of the twentieth century the theory concerning its role has evolved. It is now recognized that vitamin D, and particularly its active form 1.25 (OH)2D, is an important hormone playing a crucial role in human homeostasis. [1.25(OH)2D3 has been shown to inhibit cancer cell growth, induce cancer cell maturation, induce apoptosis, and decrease angiogenesis. Several studies suggested that living at higher geographical latitudes increased the risk of developing and dying of colon, prostate, breast and other cancers. People exposed to sunlight were noted to less likely develop cancer. Several studies evaluated circulating levels of 25(OH)D and its possible association with cancer. Case-control studies and laboratory tests have consistently demonstrated that vitamin D plays an important role in the prevention of breast cancer. Vitamin D supplementation is a much needed, low cost, effective, and safe intervention strategy for breast cancer prevention that should be implemented. It has been shown that vitamin D levels are lower in ovarian cancer patients. Low 25(OH) D concentration associated with lower overall survival rate might suggest for the important role of severe deficiency in more aggressive course of ovarian cancer. Testing for 25(OH)D in the standard procedure could help to find ovarian cancer patients with worse prognosis, who would benefit from special attention and supplementation. Vitamin D3 supplementation in moderate doses achieving 25(OH)D concentrations of 30-80 ng/ml, can be recommended as many benefits may be expected, including decreased risk of developing cancer.

Unlabelled: Breast cancer resistance protein (BCRP, ABCG2) is a xenobiotic half-transporter protein. It is a member of the ATP-binding cassette protein family and functions as an energy-dependent efflux pump. BCRP is involved in multidrug resistance. The study aimed at examining BCRP expression in breast cancers and at defining a relationship between activity of this protein and clinical course of the cancer., Materials and Methods: We analyzed the expression of BCRP in 101 stage II breast cancer patients. All the patients were diagnosed and treated at the Lower Silesia Oncology Centre (LSOC) between January 1993 and June 1994. After the treatment the patients remained under constant control at LSOC. Mean duration of the observation was 14.2 years (ranging between 9.1 and 16.5 years). Data related to relapse of the disease and deaths were obtained from medical documentation stored in LSOC. The immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against BCRP. The intensity of immunohistochemical reactions with BCRP antibody was evaluated using the semi-quantitative IRS (ImmunoReactive Score) scale, which took into account the intensity of the colour reaction and percentage of positive cells. Results of the immunohistochemical reactions, pathological and of clinical observations were subjected to statistical analysis. Correlations between these factors and BCRP were analyzed using Spearman and Chi2 tests. In order to estimate the survival rate, we used Kaplan Meier statistics, log-rank tests and Cox proportional hazard regression., Results: In our analysis we observed a positive correlation between the expression of the BCRP protein and grade of tumour advancement (r = 0.2 p = 0.03). We found also a negative correlation between the expression of BCRP and the estrogen (r = 0.24 p = 0.02) and progesteron (r = 0.28 p = 0.02) receptors. In a univariate analysis a significantly shorter disease free survival (DFS) and disease specific survival (DSS) was noted in patients with metastases to the lymph nodes (p = 0.003 and p = 0.0006), over the age of 50 years old ((p = 0.02 and p = 0.04) and clearly statistically significant in patients with a high expression of BCRP (p = 0.00044 and p = 0.00005). Overall survival (OS) was shorter in patients over the age of 50 (p = 0.01), with higher stage of the disease - IIB (p = 0.025), with metastases to the lymph nodes (p = 0.003) and also clearly statistically significant in patients with a high expression of BCRP (p = 0.00004). A multivariate analysis allowed to reveal that only higher expression of BCRP and metastases to lymph nodes were typical for cases of DFS (p = 0.,028 and p = 0.00015), DSS (p = 0.00052 and 0.000017) and OS (p = 0.0018 and p = 0.000007) time., Conclusions: We demonstrated that high BCRP expression level is associated with poor survival in early stage breast cancer patients.

Breast cancer is the most common neoplasm among women. The risk of disease increases with age, particularly in postmenopausal period. The method of treatment depends on the stage of disease, state of receptors and molecular subtype. Depending on indications there are few options: surgical treatment, radiotherapy, hormonotherapy, chemotherapy and targeted therapy. Systemic treatment of metastatic triple-negative breast cancer is not satisfying. Hopes are laid upon poly(ADP-ribose) polymerase inhibitors. Studies over these substances in both: in connection with the standard chemotherapy and as monotherapy bring promising results. The article presents the molecular basics of polymerase poly(ADP-ribose) function as well as the possibilities of using its inhibitors in treatment of triple-negative breast cancer.

A case of a 36-year old woman with HER2-positive early breast cancer treated with adjuvant trastuzumab left ventricle dysfunction and cardiac arrest in ventricular fibrillation mechanism is presented. After having been successfully resuscitated, trastuzumab therapy was withheld, pharmacotherapy (beta-blocker, ACE-I) implemented and ICD was implanted. Echocardiography performed 6 months later, revealed normal systolic function of the left ventricle. The patient died despite further oncologic treatment due to progression of the disease. The authors discuss the approach to this dramatic but lone cardiac side effect of trastuzumab treatment.

Conjugated linoleic acid (CLA) is a collective term describing a mixture of positional and geometric isomers of linoleic acid with two conjugated double bonds. Among these compounds two isomers cis9, trans11 and trans10, cis12 have received considerable attention. They are present in milk and meat fat of ruminants and the cis9, trans11 (rumenic acid) is the most abundant with lesser amounts of the trans10, cis12 isomer. A considerable number of papers suggest anticarcinogenic properties of CLA, including their ability to suppress the growth of different cancer cell lines in vitro. It was also found that these isomers may act through different mechanisms to inhibit carcinogenesis. In view of the above, the objective of this paper was evaluation of isomer-specific effects of the natural CLA isomers i.e. cis9, trans11 and trans10, cis12 on proliferation of mammary cancer cell lines. Two mammary cancer cell lines were used: MCF-7 and T47D (ATCC Collection). The cells were incubated with both CLA isomers: cis9,trans11 or trans10, cis12 within the range of 5-200 microM for 24-120 h. There were no toxic effects of any of the isomers in the range of 5-100 microM, as indicated by the Cytotoxicity Detection Kit (Roche) and cells proliferation was determined in these experimental conditions. Proliferation of cells was determined using Cell Proliferation ELISA BrdU (5' bromo-2' deoxyuridine), based on incorporation of BrdU to DNA of growing cells. The results obtained indicate that both isomers suppress the proliferation of the studied mammary cancer cell lines i.e. MCF-7 and T47D, especially when treated with the CLA isomers for 48 h or longer. Of the studied lines the strongest growth-suppressing function approximately 65% was observed for the line T47D.

Estrogens control a large range pivotal life functions as reproductive development and fertility, bone growth and sexual behavior. Aromatase is a key enzyme of estrogen biosynthesis. The property, structure and reaction mechanism of aromatase as well as detailed structure of human aromatase cytochrome P450 gene (CYP19) was discussed in this article. It was pointed that unique human CYP19 gene expression results from presence of many tissue specific promoters and alternative splicing. The molecular mechanism of control aromatase cytochrome P450 gene expression in various species ovaries, testes and human adipose tissue and placenta was discussed in details. Because of a very important role of estrogen in breast cancer a molecular base of aberrant expression CYP19 gene in breast tumor and adipose tissue proximal to breast tumor and potential possibility of pharmacological silencing of this gene expression was discussed in the article.

Serum concentrations of interleukin 6 (IL-6) and C-reactive protein (CRP) were determined in 74 patients with various histological types and clinical stages of breast carcinoma, recurrent breast carcinoma and of benign breast tumor. The concentrations of IL-6 and CRP were significantly increased in carcinoma patients relative to control group and to benign breast tumor group. The frequency of higher levels and absolute value of IL-6 and CRP showed tendency to significant increase with the stage of disease. A positive correlation was observed between the concentrations of IL-6 and CRP. Our results suggest that of IL-6 assay may be useful in estimation of progress disease in patients with breast carcinoma.

Overexpression of the Erb B-2 receptor plays an important role in the pathogenesis of breast cancer. It results in the formation of heterodimers consisting of Erb-B2/Erb B-3 receptors which have an ability to produce stable and external factors independent mitotic stimuli. Together with an autocrine stimulation of neoplastic cell proliferation by heregulin and cyclooxygenase 2 activation it is a significant factor in carcinogenesis. Overexpression of Erb B-2 seems to be an independent negative prognostic factor in breast cancer. Its predictive value is not clear-cut. It is suggested that breast cancer showing Erb B-2 overexpression is more sensitive to treatment with anthracyclines and less to CMF. The anti-Erb B-2 monoclonal antibody (trastuzumab) is used in treatment of metastatic breast cancer both as a single drug and in combination with chemotherapy.

The gamma-aminobutyric acid (GABA) is the major and the best known neurotransmitter with inhibitory properties in the central nervous system (CNS). Outside the CNS, GABA acts as a regulator of muscle tension and controls the secretion of hormones. In the peripheral region, as in the CNS GABA's function is known to be mediated by GABAA and GABAB receptors. Several recent reports have suggested a relationship between the GABA-ergic system and oncogenesis. It has been confirmed that both GABA content and GAD activity are increased in material from colon, breast, digestive tract, and ovarian cancer. In the light of theory of dynamic balance between stimulating and inhibitory amino acids, disturbances in GABA metabolism may be a sign of the cell's defensive reaction during carcinogenesis.

The aim of the review is to outline the current knowledge about the role of nitric oxide in the processes of proliferation and apoptosis in tumor. Special emphasis has been placed on its direct cytotoxic influence on a cell where as a highly active free radical it may compromise different cellular functions. Nitric oxide literature, regarding its role in the pathogenesis of some gynecological and breast cancer has been briefly reviewed.

It seems, that quantitative changes of growth hormone (GH) in blood and imbalance between GH and hormones can influence the breast cancer cells proliferation, and can be a favourable element in breast cancer progression. The procedure to normalize hormonal system can have a therapeutic action. The aim of the presented work is to asses the plasma GH levels in 24 pre-menopausal women after mastectomy for breast cancer on adjuvant chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil (CMF). In this study interactions between GH and insulin like growth factor-I, prolactin, estradiol, progesterone (P), melatonin, cortisol and met-enkephalin were assessed. The control group was consisted of 16 healthy women. Plasma GH concentration and interactions between GH and studied parameters in women with breast cancer did not differ from healthy women. Highly significant positive correlation between GH and P after administration CMF was shown. CMF did not influence the interactions between GH and other studied parameters.

The aim of our study was to determine phenazone pharmacokinetics as an index of hepatic microsomal enzymes activity and acetylation phenotype in women with breast cancer. Phenazone test was made in 41 women with breast cancer and in 25 healthy women as a control group. Acetylation phenotype was measured in 40 women with breast cancer and in 25 healthy women as a control group. The plasma concentration of phenazone was estimated by the spectrophotometric method of Brodie and associates. Acetylation phenotype was determined by the Bratton-Marshall method in Varley's modification. The mean phenazone half-life time (t0,5), shortened significantly and the mean elimination rate constant (K) increased in women compared with a group of healthy persons. Mean clearance rate was increased in women with breast cancer too, compared with a group of healthy women. Acceleration of phenazone elimination may suggest that in patients with breast cancer elimination of the other drugs metabolized by the pathway similar to phenazone also may be changed. This should be considered in selection of their dosage. We have observed the predominance of rapid acetylators in women with breast cancer comparing with healthy persons. This difference was not statistically significant. Our results of acetylation phenotype in women with breast cancer suggests that rapid acetylation may be a factor of susceptibility to breast cancer.

Serum CA 15-3 concentrations were determined using sandwich enzyme immunoassay in 430 women: 214 breast cancer patients prior to any therapy, 161 patients with benign breast diseases, and 55 healthy controls; the cut-off limit was established at 30.0 U/ml. In breast cancer patients, CA 15-3 levels positively correlated with negative prognostic factors: higher tumor size (p < 0.001), positive axillary lymph nodes (p < 0.02), high histological grade (p < 0.01), low contents of estrogen (p < 0.05) and progesterone (p < 0.006) receptors. However serum CA 15-3 values raised in parallel with clinical stage of breast cancer, the difference was not significant. The overall diagnostic sensitivity and specificity of the test were 24.3% and 94.9%, respectively. The mean serum CA 15-3 values and the percentage of positive results in breast cancer patients were significantly higher as compared to benign breast diseases group (27.52 +/- 27.01 vs. 16.75 +/- 8.43, p < 0.001; 24.3% vs. 5.6%, p < 0.001, respectively) as well as to healthy controls (27.52 27.01 vs. 13.37 +/- 6.51, p < 0.001; 24.3% vs. 3.6%, p < 0.01, respectively). The sensitivity of the CA 15-3 test is low and thus not suitable for the differential diagnosis of breast lumps. Our data suggest potential prognostic value of pretreatment CA 15-3 assays in breast cancer patients.

Immunocytochemical methods (ER-ICA) by using monoclonal antibodies were applied to determine the presence of estrogen receptors (ER) in 44 primary breast cancers in women. Of this 48% of the tumours were classified as receptor positive. In these tumours the nuclei had a clearly positive heterogenous colouration. In three cases a positive reaction was also found in benign epithelial cells of the breast. ER determinations by ER-ICA method were compared with quantitative analysis carried out by using radioligand and immunoenzymatic methods. There was a strong correlation between immunocytochemical ER evaluations and quantitative methods. We also found a correlation of the menopause state and patients age and ER content.