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Biomedical subjects

E Kubista

Publications and source records attributed to E Kubista.

At least 37 records · Page 2Linked to original sources
PubMed2001

Color Doppler sonography of the lateral thoracic (breast-feeding) arteries: a new approach to the diagnosis of breast disease?

OBJECTIVE: The main arteries to the breast are the lateral thoracic artery and to a lesser extent the internal thoracic artery. In this prospective open diagnostic study involving 94 women, we compared the intraindividual differences of Doppler indices in the lateral thoracic (breast-feeding) artery of breasts affected by cancer with those unaffected by disease. METHODS: Sixty-seven consecutive patients were recruited from an outpatient unit for breast surgery and 27 volunteers were studied who were known to be without any breast disease (controls). In each patient we attempted to obtain Doppler indices from the lateral thoracic artery of both breasts. The difference in Doppler indices in each individual was assessed and statistical analysis was performed to assess whether these differences were significantly altered in women with cancer compared to healthy women. RESULTS: Lateral thoracic arteries could be visualized in 88% of the study population. Significantly lower values for pulsatility and resistance indices and systolic/diastolic ratios were obtained in the lateral thoracic arteries of breasts affected by cancer as compared to the contralateral breasts (1.73 +/- 0.39 vs. 2.05 +/- 0.47, P = 0.003; 0.78 +/- 0.06 vs. 0.84 +/- 0.06, P < 0.0001; 4.71 +/- 1.24 vs. 6.75 +/- 3.38, P = 0.0008, respectively). Using the intraindividual difference of pulsatility index, resistance index and systolic/diastolic ratio to screen for malignancy, sensitivities for breast cancer of 78%, 85% and 83%, respectively, were achieved. Depending on the cut-off level, specificity reached 94%. CONCLUSION: The intraindividual difference in Doppler indices in women with breast cancer may be a useful test for the diagnosis of breast lesions.

Adolescent↗
PubMed2001

Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer.

PURPOSE: The purpose of this study was to investigate the prognostic significance of assessment of human epidermal growth factor receptor (HER)-2 oncogene protein overexpression of breast cancer tissue by the United States Food and Drug Administration (FDA)-approved HercepTest and grading system (negative, 0 or 1+; weakly positive, 2+; strongly positive, 3+). Furthermore, results of the HercepTest were correlated with immunohistochemical results obtained using different antibodies and protocols and with HER-2 oncogene gene amplification assessed by fluorescence in situ hybridization (FISH). EXPERIMENTAL DESIGN: HER-2 status in 303 patients with lymph node-positive breast cancer was investigated by using a rabbit polyclonal antibody (DAKO) by conventional immunohistochemistry and by applying the HercepTest. Furthermore, the monoclonal antibody CB-11 was used in conventional immunohistochemistry and with the NexES automatic stainer, which is also under consideration for FDA approval for determination of eligibility for Herceptin therapy. Results were compared with FISH analysis performed in all 2+ and 3+ specimens (103 cases) and 104 HER-2-negative specimens. RESULTS: 3+ positive carcinomas were found in 8.9-15.7% of specimens. FISH revealed that almost exclusively 3+ positive cases were amplified, with the HercepTest and the NexES automatic stainer giving the best results. In univariate analysis, staining with the HercepTest revealed a significantly worse prognosis in 3+ cases. Also, 3+ cases were significantly associated with lower estrogen receptor levels and histological grade III tumors. CONCLUSIONS: This study shows that the results of the FDA-approved HER-2 grading and test system correlated strongly with findings in FISH. Furthermore, HercepTest proved to be of prognostic relevance. Strict adherence to the given protocols is critical.

Adult↗
PubMed2001

Comparative analysis of two-dimensional protein patterns in malignant and normal human breast tissue.

Malignant and normal human breast tissue were compared by evaluating two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) maps of frozen tissue samples. Image analyzing software was used to scan and process 34 gels. Eight (8/34) of these gels (4 malignant breast tumor samples, 4 normal tissue samples) were selected on the basis of gel and image quality to build a database to identify and measure the expression of a previously unidentified proteome. Growth factor receptor proteins (GFRs), including ERBB2 (HER2) and ERBB3 (HER3), were expressed in the malignant tissue samples. Growth factor receptor proteins were not expressed in the normal tissue. Also, expression of PS2-protein (pS2) was detected in neither malignant nor normal tissue. In benign breast samples a higher intensity of protein expression could be observed for maspin, desmoglein 3 and keratin 8 than in malignant samples. Other proteins expressed in malignant breast tissue include mitogen-activated protein kinase 3 (MK03), heat shock protein 27 kDa (HS27), growth factor receptor-bound protein (GRB2), cathepsin D, G1/S specific cyclin E1 (CGEI), glucose transporter type 5 (GTR5), and a number of as yet unidentified proteins.

Breast↗
PubMed2001

Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.

Austria↗
PubMed2001

[Breast cancer: figures and facts].

The diagnosis and therapy of breast cancer has been improved and individualized to a great extend during the past two decades. Large randomised trials guide our discussions and new results are integrated continuously into the concept of breast cancer diagnosis and treatment. The new achievements are an increased early detection of breast cancer, a reduction in invasive procedures for diagnosis and operative treatment and an improvement of reconstructive oncoplastic-procedures. Chemo- and hormonal therapy have increased the survival rate and have improved quality of live in advanced disease. The follow-up of patients with breast cancer has to be aimed on regular personal contact, mammography, and gynaecologic follow-up. Other laboratory parameters and imaging techniques have to be reduced and confined for patients with anamnestic or clinical evidence of tumour progression.

Austria↗
PubMed2000

Axillary lymph nodes in breast cancer: is size related to metastatic involvement?

Usually when using imaging procedures, such as axillary mammography or ultrasonography, a cutoff level of 5 mm for lymph node size is postulated to be not only the limit of lymph node visibility but also a sign of metastatic involvement. The aim of this study was to evaluate whether this assumption, used as a basic hypothesis in many reports, is true. A series of 72 axillary specimens from 71 breast carcinoma patients operated at the university hospital of Vienna were analyzed. A comparison of histologically noninvolved axillary specimens with those showing metastatic involvement revealed that the two groups did not differ significantly according to the number or size of lymph nodes per axilla. For lymph nodes <5 mm the probability of being metastatically involved was still 10%. Enlarged lymph nodes (5-20 mm) had a slightly higher risk of being malignant (20%). In contrast, the probability of metastatic involvement for lymph nodes >20 mm was only 40%. We suggest that many reports dealing with the prediction of malignancy in axillary lymph nodes may have used misleading basic assumptions, so the results of these studies must be viewed critically.

Axilla↗
PubMed2000

Local feedback mechanisms in human breast cancer.

Breast function and development are controlled by a variety of both local and systemic signals. Many of these signals are exerted by hormones and cytokines which are believed to be effectors in autoregulatory feedback loops. Recent studies have also suggested the involvement of such mechanisms in human breast cancer. For example, the disruption of a negative feedback system by malignant transformation can result in the loss of growth control or in increased malignant behavior of tumor cells. Conversely, pathological positive feedback loops can develop that enhance tumor growth and invasion by excessive release of stimulatory factors. These loops are often located at the site of tumor invasion and involve stromal-epithelial interactions. They can be composed of mutually stimulating or inhibiting cytokines and may include locally expressed sex steroids. Although most studies have concentrated on cell-cell interactions at the site of the primary tumor, a number of observations indicate their importance in metastases as well. A thorough analysis of the regulatory mechanisms within a malignant tumor is essential for the understanding of its unique behavior and for the investigation of more specific breast cancer therapies.

Breast Neoplasms↗
PubMed2000

99m-Tc-tetrofosmin scintigraphy for the evaluation of suspicious palpable and non-palpable breast lesions.

PURPOSE: To assess the value of 99m-Tc-tetrofosmin (tetrofosmin) scintigraphy in patients with palpable and nonpalpable breast lesions. PATIENTS AND METHODS: Prospective, blinded trial. One hundred and fifty-nine consecutive patients with 163 breast lesions detected by clinical examination and mammography were included. Tetrofosmin scintigraphy of the breast was performed additionally to the regular diagnostic procedure. Using histologic assessment as the golden standard, sensitivity, specificity, positive and negative predictive value for tetrofosmin scintigraphy of the breast were assessed. RESULTS: Overall sensitivity and specificity were 82% and 84%. The sensitivity for palpable tumors (65%) was 93% compared to 62% for non-palpable breast lesions. Malignant lesions were nearly twice as big as benign lesions (31.5 mm +/- 2.4 vs. 16.9 mm +/- 2.4). Specificity, positive and negative predictive value (84%, 89%, and 66%) did not differ significantly in palpable versus non-palpable tumors. Of malignant tumors 18% were found false negative by tetrofosmin scintigraphy. CONCLUSION: The results suggest that tetrofosmin scintigraphy is a valuable tool for the evaluation of palpable breast cancer. In patients with non-palpable tumors, tetrofosmin scintigraphy may not add to the work-up of patients with breast cancer due to a low sensitivity rate.

Adult↗
PubMed2000

Single-agent gemcitabine as second- and third-line treatment in metastatic breast cancer.

In the present study, 25 patients with breast cancer pretreated with one or two anthracycline-based regimens for visceral metastases were enrolled. Patients were treated with gemcitabine 1250 mg/m2 on days 1, 8 and 15, q28d. Nine patients received gemcitabine as second-line treatment, whereas 16 patients received gemcitabine as third-line cytotoxic treatment, respectively. In the second-line setting, two (22%) patients gained PR (RR 22%) and four (44%) patients experienced SD (P=0.2), respectively. In the third-line-setting, one (6%) patient gained CR, one patient PR (6%) and four patients (25%) SD, respectively, resulting in a response rate (RR) of 12%. In the second-line-setting, median time to progression was 5.1 +/- 4.0 months (range: 1.6-13.9) versus 3.5-2.5 months (range: 1.3-10.4) in the third-line-setting. Median overall survival was 12.6 +/- 9.1 months (range: 3.9-30.8) versus 7.5 +/- 6.7 months (range: 2.0-26.0), respectively. Overall, no patient experienced treatment limiting toxicities. We conclude from the present study that gemcitabine induced an overall RR of 16% following prior treatment with anthracyclines. However, median time to progression and median overall survival were limited. In the search for efficacious treatment of patients with metastatic breast cancer, gemcitabine constitutes a valid tool in anthracycline-resistant disease and thus might represent a valuable option for combination chemotherapy in controlled trials in this condition.

Journal Article↗
PubMed2000

Paclitaxel-containing high-dose chemotherapy in high-risk breast cancer patients.

Despite standard-dose adjuvant chemotherapy, the prognosis for patients with breast cancer and extensive axillary lymph node involvement at diagnosis is poor. The efficacy of a paclitaxel-containing, high-dose chemotherapy protocol in 21 high-risk breast cancer patients is assessed. After standard-dose chemotherapy followed by peripheral blood stem cell (PBSC) mobilization, high-dose therapy with paclitaxel, carboplatin, and cyclophosphamide and CD34-selected PBSC rescue was given. Hematologic reconstitution after high-dose therapy was rapid. Main toxicity included diarrhea grade I or II in about half of the patients and infections were observed in 19%. Five-year probabilities for relapse and failure-free survival were 32% and 62%, respectively. High-dose consolidation with paclitaxel, carboplatin, and cyclophosphamide achieves a high failure-free survival in patients with high-risk breast cancer with acceptable toxicities and stable, long-term hematopoietic reconstitution. Evaluation of the benefit of high-dose therapy in these patients in larger prospective, randomized trials is warranted and currently under way.

Adult↗
PubMed2000

Use of 99mTc-furifosmin scintigraphy--planar and SPECT--to evaluate suggestive palpable and nonpalpable breast lesions.

UNLABELLED: Our objective was to evaluate the role of 99mTc-furifosmin scintigraphy--planar and SPECT--in discriminating benign from malignant breast disease. METHODS: The trial was prospective, open, and diagnostic. We recruited 30 consecutive patients with 14 palpable and 16 nonpalpable breast lesions. After receiving informed consent, we injected 555-640 MBq 99mTc-furifosmin intravenously in the arm contralateral to the breast lesion. Planar imaging and SPECT were performed. All patients underwent excision of the tumor within 2 wk. Using histology as the gold standard, we calculated sensitivity, specificity, and positive and negative predictive values for 99mTc-furifosmin in planar and SPECT technique. RESULTS: For 18 malignant and 12 benign breast lesions, a sensitivity of 50% for planar imaging and 72% for SPECT was seen. Specificity and positive and negative predictive values were 83%, 82%, and 53%, respectively, for planar imaging and 50%, 68%, and 55%, respectively, for SPECT. For the 14 palpable tumors (10 malignant, 4 benign), which averaged 17+/-10 mm in size (size range, 4-45 mm), a sensitivity of 60% for planar imaging and 80% for SPECT was achieved. Sixteen lesions were not palpable (median size, 9+/-3 mm [size range, 4-13 mm]). In this subgroup, 99mTc-furifosmin scintigraphy yielded a sensitivity of 37% for planar and 62% for SPECT technique (P>0.05). CONCLUSION: 99mTc-furifosmin scintigraphy is not a potent competitor to established scintigraphic procedures. In comparing this tracer with 99mTc-sestamibi and 99mTc-tetrofosmin, we cannot recommend 99mTc-furifosmin for the diagnosis of breast cancer.

Breast Diseases↗
PubMed1999

Estrogen replacement therapy in women with a history of breast cancer.

Estrogens are known as potent mammary mitogen substances and are the major stimulus for the growth of hormone-dependent tumors and clearly implicated in the pathogenesis of breast cancer. Therefore it is a general belief that hormone replacement therapy (HRT) after breast cancer will increase the risk of developing recurrences, though there are no clear data available to support this suggestion. No prospective study with a large number of patients and a long treatment period was performed concerning this issue. On the other hand it may not be justifiable to withhold hormone replacement therapy from low-risk patients after menopause, knowing the benefits of this therapy concerning osteoporosis and cardiovascular advantages. Nevertheless, until appropriate clinical trials help to resolve this problem, non hormonal alternatives constitute the standard of care. One possible approach is to treat menopausal women who have had breast cancer symptomatically and avoid ERT unless absolutely necessary. The risk of cardiovascular diseases can be reduced with lifestyle. Tamoxifen has a beneficial effect on serum lipids and the intake for 5 years leads to a 50% reduction in the incidence of fatal myocardial infarction and a decrease in morbidity associated with ischaemic heart disease. Low doses of progestogen is effective for menopausal hot flushes. Tibolone reduces vasomotoric symptoms such as hot flushes and offers benefit on osteoporosis and has shown a significant reduction in high-density lipoprotein cholesterol. Whether replacing of estrogens is safe for patients after breast cancer remains uncertain. There is a need for a large controlled clinical trial to evaluate the safety and advantages of long time estrogen replacement in women treated for breast cancer.

Breast Neoplasms↗
PubMed1999

Axillary metastases of an occult primary carcinoma of the breast-discovered only by 99mTc-tetrofosmin scintigraphy.

Recent reports consider 99mTc-tetrofosmin scintigraphy to be a powerful new diagnostic tool for discriminating malignant from benign breast disease. We report on a woman suffering from histologically confirmed axillary metastases of a primary unknown, occult carcinoma, whose origin was suspected within the breast. All the diagnostic procedures performed to discover any lesion failed or were inconclusive. The primary cancer was clearly visualized, however, in the right breast by means of 99mTc-tetrofosmin scintigraphy. Conclusion. We suggest that 99mTc-tetrofosmin scintigraphy is a powerful method to detect breast cancer, especially when other diagnostic imaging procedures are inconclusive.

Axilla↗
PubMed1999

99m-Tc-tetrofosmin scintigraphy and breast cancer.

BACKGROUND: 99m-Tc-tetrofosmin holds significant interest among medical oncologists because of its high positive predictive value (>90%) in pilot trials, exceeding sensitivity and specificity rates of mammography. Objective. Our objective was to assess the diagnostic accuracy of 99m-Tc-tetrofosmin whole-body scintigraphy in outpatients. PATIENTS AND METHODS: Thirty-one patients with an abnormal mammograph (n = 22) or follow-up patients (n = 9), 7 of whom were known to have metastatic disease, were included. Tracer (550 MBq) was injected into the cubital vein. Whole-body planar and single photon emission computed tomography images of regions of interest were obtained. Histology, computed tomography (CT), or magnetic resonance imaging (MRI) were performed to confirm scintigraphic results. Correlation between scintigraphy and CT or MRI was assessed by two independent radiologists. Accuracy, sensitivity, and specificity rates for the diagnosis of local and distant breast cancer lesions were given. RESULTS: Of the 22 first-visit patients, 15 had breast cancer, and 7 had no evidence of any malignant disease. Of all patients examined (n = 31), 21 had distant metastases. Breast tumors were correctly diagnosed in 14/15 patients (93%), with only 1 false-negative result. Extrahepatic metastatic lesions (n = 16) were correctly diagnosed in 14 (88%) patients, whereas the method was not suitable for the diagnosis of liver metastases. CONCLUSION: Tetrofosmin scintigraphy has shown very high detection rates of breast tumors and of metastatic lesions and is therefore a valuable option in breast cancer diagnosis.

Adult↗