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Search Results: 1 - 10 of 3854 matches for " Ne?kovi?-Konstantinovi? Zora "
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Primary endocrine therapy of locally advanced breast cancer patients
Nekovi?-KonstantinoviZora B.
Archive of Oncology , 2003, DOI: 10.2298/aoo0303139n
Abstract: Primary endocrine therapy has been traditionally reserved for elderly and unfit locally advanced breast cancer patients (LABC patients). In this group, the primary endocrine therapy could not be adequately compared to primary chemotherapy. Rare studies of primary endocrine therapy, and careful subgroup analyses of their results, showed that primary endocrine therapy could achieve at least the similar magnitude of response rate, compared to primary chemotherapy, in selected patients' population. Thus, the primary treatment with tamoxifen in steroid receptor (SR)-positive LABC patients became the standard arm in current studies of primary endocrine therapy. Several questions, concerning the use of endocrine primary treatment in routine clinical practice, should be answered, including the definition of optimum endocrine agents, biomarkers for prediction of response, and patients' selection criteria.
Prognostic role of epidermal growth factor receptor in localized breast cancer: 15 Years of follow-up
Nekovi?-KonstantinoviZora,Kanjer Ksenija,Borojevi? Nenad,Jezdi? Svetlana
Archive of Oncology , 2006, DOI: 10.2298/aoo0604110n
Abstract: Background: The expression of epidermal growth factor receptor (EGF-R) in breast cancer (BC) is generally considered as an unfavorable event during tumor progression. Its predictive role has been fairly well defined: EGF-R expression predicts tamoxifen unresponsiveness. EGF-R role in autocrine growth regulation was confirmed. However, reported results on its prognostic role in BC patients were conflicting. The prognostic role of EGF-R after 15 years of follow-up is analyzed in a group of 70 localized BC patients, presented at diagnosis in clinical stages I-III. Methods: BC patients newly diagnosed from December 1990 until March 1991, treated in accordance to the National Protocol, were selected for EGF-R analysis. Steroid receptors and EGF-R were determined at diagnosis in same frozen tissue samples, using biochemical methods. Except 6 patients who were lost from follow-up in the interval shorter than 60 months, the remaining patients were followed-up from 60-188 months. The total number of events was 32 relapses (46%), and 27 deaths (38.5%). Results: EGF-R expression was found in 28/70 patients (40%), and the EGF-R content higher than 26 fmol - in 15/70 patients (21%). Neither the expression, nor the high content of EGF-R showed any influence on disease-free or overall survival. Levels of EGF-R were similar in relapsing and relapse-free patients. Nodal status had the strongest infuence on prognosis. Conclusion: Our results suggest that the controversial findings, regarding the EGF-R prognostic role, might be the consequence of a genuine weak influence of EGF-R expression on disease outcome. .
Estrogen receptor as the predictive factor for response to chemotherapy in breast cancer
?u?njar Sne?ana,Nekovi?-KonstantinoviZora
Archive of Oncology , 2006, DOI: 10.2298/aoo0604156s
Abstract: It has generally been accepted that breast cancer (BC) cells are equally responsive to chemotherapy (CHT) irrespective of ER status. However, subset analyses of disease outcome in recently reported trials on neoadjuvant and adjuvant CHT brought new information about the issue. The subject of this paper is to review these data and to communicate our own results. NSABP B27 was designed to evaluate if adding of docetaxel (D) to conventional neoadjuvant doxorubicin-cyclophosphamide (AC) CHT improves the clinical response rate (cRR) and pathological RR (pRR) in BC patients treated with 4 AC cycles only. Although the adding of D to AC C.T significantly improved RR in both ER-negative and ER-positive BC patients, the pCR was significantly higher in ER-negative than in ER-positive group (16.7% vs. 8.3%) irrespective which regimen was used. ECTO trial and several neoadjuvant studies confirmed the significantly inferior RR to neoadjuvant C.T in ER-positive compared to ER-negative BC patients. Three large randomized Cancer and Leukemia Group B (CALGB) studies (CALGB 8541, CALGB 9344, and CALGB 9741) compared the efficacy of different adjuvant anthracycline-containing or anthracycline/taxane-containing regimens in BC patients. The absolute benefit in 5-year disease-free survival in ER-negative and ER-positive BC patients treated with adjuvant C.T were 22.8% and 7.0%, while corresponding absolute benefits in overall survival were 16.7% and 4.0%. The concept of equal sensitivity of ER-negative and ER-positive BC to CHT has been changing. The future task is to find BC patients with ER-positive BC with no benefit from CHT in whom endocrine therapy is the therapy of first choice. .
In vivo model for research of breast cancer biomarkers
Kanjer Ksenija,Nekovi?-KonstantinoviZora,Nikoli?-Vukosavljevi? Dragica
Archive of Oncology , 2006, DOI: 10.2298/aoo0604141k
Abstract: The preoperative (neoadjuvant) setting of breast cancer treatment is an optimal in vivo model by which to allow the characterization of biomarker expression pattern with the tumor remaining in situ throughout treatment as an in vivo measure of response to particular therapy. Elucidating surrogate molecular or cellular markers of tumor response to therapy, may provide biological insight into both, the mechanism of tumor growth dynamics and drug sensitivity/resistance. Owing to the knowledge that many drugs are effective on actively proliferating cells and more intriguingly, that many anticancer agents with differing modes of action achieve cytotoxic effects by inducing apoptosis, has lead to a reappraisal of traditional views of tumor response/resistance to cytotoxic drugs in vivo. Accordingly, this review article will focus on discussing apoptosis phenomena and the p53 and bcl-2 protein as its regulators of principal impor-tance; a cell proliferation determined by the Ki-67 expression, as the major counterbalancing process to apoptosis is also considered. This paper reviews the rationale for the use of these proteins as indices of tumor response to therapy, as well as the published literature regarding their clinical relevance. So far, no firm conclusions can be made concerning their predictive utility. .
The role of hormonal ovarian ablation in adjuvant treatment of premenopausal breast cancer
Murtezani Zafir,Nekovi?-KonstantinoviZora,Stanisavljevi? Nata?a,Kov?in Vladimir
Srpski Arhiv za Celokupno Lekarstvo , 2011, DOI: 10.2298/sarh1106339m
Abstract: Introduction. Breast cancer is the most frequent malignant disease in women with about 25% compared to all malignant tumours. Chemotherapy, antiestrogen and ovarian ablation/ supression present effective adjuvant approach for premenopausal women diagnosed with hormonal depended, operable breast cancer. Objective. To evaluate benefits of combined chemo/hormonal therapy that is undutiful, but optimal application has not yet been clearly determined. Methods. Thirty-six women were divided into three therapy groups. The first group (13 women) was treated with six cycles of adjuvant FAC chemotherapy followed by regular check-ups; the second group (13 women) after six cycles of adjuvant FAC chemotherapy continued treatment with a two-year application of goserelin given by subcutaneous injections (FAC-Z); the third group (10 women), after six cycles of adjuvant FAC chemotherapy continued with once per month application of gorselin for two years and a daily application of 20 mg tamoxifen for five years (FAC-Z-T). The length of overall disease free period and survival were analyzed in all three groups. Results. The benefit of LH-RH analogues in premenopausal women with hormone-dependent breast cancer was found to be low, and probably limited to smaller subgroups of patients, possibly such as those with either both steroid receptors positive (ER and PR) or those with an extremely high level of steroid receptors. In our paper, analyses of such subgroups could not been performed due to a small sample of patients. The effect of therapy is better in patients, who developed amenorrhoea, regardless of the type of later hormonal therapy. Conclusion. Ovarial ablation, whatever the method, should be probably applied as early as possible within the treatment of early breast cancer, especially in patients in whom chemotherapy induced amenorrhoea is not expected, i.e. in very young female patients.
Levels of estrogen receptor B splice variant (ERBΔ5) mRNA correlates with progesterone receptor in breast carcinomas
Mandu?i? Vesna,Popov-?eleketi? Du?an,Nekovi?-KonstantinoviZora,Kanjer Ksenija
Archives of Biological Sciences , 2010, DOI: 10.2298/abs1002257m
Abstract: It is well known that breast tumors which are estrogen positive ER(+) are more likely to respond to hormone therapy. However, a certain percentage of ER(+)/PR(+) tumors do not respond to this therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ERβ), as well as the existence of numerous isoforms/splice variants of both ERα and ERβ, suggests that a complex regulation of estrogen action exists. In this study, we analyzed the expression ratio of ERβ1 isoform and ERβΔ5 splice variant mRNAs, and its correlation with ER/PR status by quantitative RT-PCR and clinical and histopathological parameters. We found that the relative proportion of ERβΔ5 in the total ERβ1 transcript 'pool' inversely correlates with the PR level (p = -0,359, p< 0,003, Spearman). It may be that the ERβΔ5 variant modulates the ERα activity of downstream targets. In addition, we suggest that the determination of the expression profiles of ERα and ERβ isoforms and splice variants in the defined groups of patients are necessary for elucidating their involvement in endocrine resistance.
High level of EGF-R expression in carcinomatous skin invasion: Does it reflect the tissue characteristics of the breast carcinoma aggressiveness?
Nekovi?-KonstantinoviZora B.,Nikoli?-Vukosavljevi? Dragica,Kanjer Ksenija,Jovanovi? Danica
Archive of Oncology , 2002, DOI: 10.2298/aoo0203111n
Abstract: Background: The normal function and distribution of EGF-R and its role in breast cancer aggressiveness, prognosis and prediction, have become extremely important in the light of the recently developed methods of EGF-R targeting. In the aim to investigate the relationship between EGF-R and the aggressive tumor behavior, the EGF-R content was analyzed as related to the presence of inflammatory breast skin involvement. Methods: EGF-R, ER and PR content was determined at diagnosis, using the biochemical methods, in the group of 103 unselected breast cancer patients, either in primary tumors (TU), lymph nodes (LN) or skin tissue samples (65, 27 and 11 cases respectively). In 10 patients with inflammatory breast cancers, TU/LN tissue was sampled from 3, and skin from 7 patients. Results: ER and PR content was significantly higher in tumor and LN tissue, compared to the invaded skin the EGF-R content was, on the contrary, significantly higher in skin than in TU or LN tissue. However, no difference was found between TU and LN in all three receptors' content. When the receptor content was analyzed in 10 patients with inflammatory breast cancer, higher levels of both ER and PR were found in tumor biopsies than in skin biopsies, while for the EGF-R the result was opposite. Significantly lower ER content and a trend towards higher EGF-R content was found in the inflammatory breast cancers in comparison to the non-inflammatory ones. Conclusion: Although we examined a small number of patients, our results suggest that the EGF-R could be a marker of breast cancer aggressiveness. However, the influence of the normal skin cells contaminating the biopsied tumor tissue cannot be ruled out. The predictive role of EGF-R deserves to be further investigated especially in locally advanced inflammatory breast cancer patients.
Cu/Zn superoxide dismutase in blood cells of patients with locally advanced breast cancer
Ni?iforovi? Ana,Filipovi? Dragana,Nekovi?-KonstantinoviZora,Radoj?i? Marija B.
Archive of Oncology , 2003, DOI: 10.2298/aoo0303150n
Abstract: Background: The clinical treatment of breast cancer frequently includes highly cytotoxic agents such as, radiation or cytostatic drugs, aiming to inhibit tumor cell proliferation and/or induce tumor cell death. The cytotoxic effects of those agents are partly achieved by the increase in concentration of oxygen free radicals (ROS), which cause massive oxidative damage of tissue DNA, proteins and lipids above the limits of cell repair capacity. Radiotherapy is of great value in the treatment of a number of malignant tumors, but its potential utilization and efficacy is limited by the necessity of avoiding the excessive late damage to normal tissues. The incidence of radiogenic damage to soft tissue has been reported as being up to 40%. To protect against toxic effects of ROS, and to modulate its physiological effects, cells have evolved the antioxidant defense system. Superoxide dismutase is an enzyme that plays an important role in biological defense against activated oxygen and/or free radicals. SOD is highly efficient in scavenging superoxide (O 2*-) radical by catalyzing the dismutation of super-oxide radicals into hydrogen peroxide (H 2 O 2) and molecular oxygen (O 2). The aim of this study was to test Cu/Zn SOD as potential biomarker of individual sensitivity to cytotoxic treatment. Methods: The intracellular Cu/Zn SOD concentration was determined in peripheral blood of patients with locally advanced breast cancer prior to any clinical treatment. The assay was performed in two groups of patients with locally advanced breast cancer, the age group 30-45 (normal cycle, n=7 stage II or III), and 45-60 (perimenopausal women, n=12, stage III or IV). The respective healthy women: age group 30-45 (n=12) and age group 45-60 (n=12) were used as controls. The concentration of Cu/Zn SOD was also assayed after in vitro radiation challenge. Results: The results showed that the intracellular Cu/Zn SOD concentration in 30-45 age and 45-60 age control groups, were cca. 12.89±0.87 arbitrary mass units/ml (AmU/ml), and cca. 10.46±0.72 AmU/ml of blood, respectively. In the two groups of patients with locally advanced breast cancer, Cu/Zn SOD concentrations were cca. 18.90±1.54 AmU/ml, and cca. 22.48±1.40 AmU/ml of blood. Thus the intracellular Cu/Zn SOD concentration did not vary significantly within the control groups or within the patient groups. However, the Cu/Zn SOD concentration was significantly different between patient groups and the respective controls. The in vitro 2Gy and 9Gy 60 Co g-radiation challenge of blood cells did not lead to significant changes in
The role of estrogen receptors isoforms in breast cancer
Mandu?i? Vesna,Nikoli?-Vukosavljevi? Dragica,Nekovi?-KonstantinoviZora,Tani? Nikola
Archive of Oncology , 2006, DOI: 10.2298/aoo0604106m
Abstract: Background: Estrogen and progesterone receptor (ER/PR) status is an accepted predictive marker in breast cancer. It is well known that breast tumors, which are ER(+) are more likely to respond to endocrine therapy. However, certain percentage of ER(+)/PR(+) tumors do not respond to endocrine therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ERβ), as well as the existence of numerous isoforms/splice variants of both ERα and ERβ, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ERβ isoforms correlates with ERα/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ERα and PR protein levels and for mRNA expression of two ERβ isoforms (ERβ1 and ERβΔ5). ERα and PR proteins were measured by classical biochemical techniques, and ERβ mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ERβ1 and ERβΔ5. We found that there is no correlation of ERβ1 mRNA expression with ERα and PR protein levels. We confirmed the existence of inverse correlation of ERβΔ5 with PR and of ERβΔ5 with ERα in the group of postmenopausal patients. In the subsets of tumors defined by ERα/PR status, we found that percentage of tumors, which concomitantly expressed high levels of both transcripts, are parallel with those that do not response to tamoxifen treatment. Conclusion: Inverse correlation of ERα with ERβΔ5 and PR with ERβΔ5isoform suggests that ERβΔ5 may have inhibitory effect on ERα activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ERα and ERβ isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance. .
The influence of plasma TGF-beta1 levels on development of postradiotherapy fibrosis in breast cancer patients
Mladenovi? Jasmina,Borojevi? Nenad D.,Todorovi?-Rakovi? Nata?a,Nekovi?-KonstantinoviZora
Archive of Oncology , 2002, DOI: 10.2298/aoo0203171m
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