185 results on '"Kwasny, W"'
Search Results
52. Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor
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Kornek, GV, primary, Haider, K, additional, Kwasny, W, additional, Hejna, M, additional, Raderer, M, additional, Meghdadi, S, additional, Burger, D, additional, Schneeweiss, B, additional, Depisch, D, additional, and Scheithauer, W, additional
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- 1996
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53. 99 P - Treatment of advanced breast cancer with vinorelbine (VLB), fluorouracil (FU), l-leucovorin (LLV) and human granulocyte colony-stimulating factor (GCSF)
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Kornek, G.V., primary, Haider, K., additional, Kwasny, W., additional, Hejne, M., additional, Raderer, M., additional, Schenk, T., additional, Burger, D., additional, Depisch, D., additional, and Scheithauer, W., additional
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- 1996
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54. Combined intraperitoneal plus intravenous chemotherapy after curative resection for colonic adenocarcinoma
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Scheithauer, W., primary, Kornek, G., additional, Rosen, H., additional, Sebesta, C., additional, Marcell, A., additional, Kwasny, W., additional, Karall, M., additional, and Depisch, D., additional
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- 1995
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55. Microstructure–property relationships in TRIP aided medium-C bainitic steel with lamellar retained austenite
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Grajcar, A., Kwasny, W., and Zalecki, W.
- Abstract
This work discusses the development of the microstructure and mechanical properties of medium-carbon steel that contains silicon, aluminium and microadditions of Nb and Ti. Two cooling strategies were designed based on the thermodynamic equilibrium calculations and continuous cooling transformation diagram, which was determined for plastically deformed austenite. The cooling paths enabled the production of ferrite based and bainite based steels. The specimens were obtained via the thermomechanical rolling process with isothermal holding of steel at 450°C. Microstructure investigations were performed using light, scanning and transmission microscopy methods. The distribution and amount of retained austenite were determined using the electron backscatter diffraction technique, whereas transmission electron microscopy allowed the identification of the morphology of the ? phase. The amount of austenite and its carbon content were assessed using X-ray diffraction. Relations between microstructure and mechanical properties were formulated based on the mechanical stability of the retained austenite.
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- 2015
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56. The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial.
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Gnant, M, Pfeiler, G, Stöger, H, Mlineritsch, B, Fitzal, F, Balic, M, Kwasny, W, Seifert, M, Stierer, M, Dubsky, P, Greil, R, Steger, G, Samonigg, H, Fesl, C, and Jakesz, R
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BREAST cancer research ,ANASTROZOLE ,BODY mass index ,POSTMENOPAUSE ,RANDOMIZED controlled trials - Abstract
Background:We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment.Methods:The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety.Results:In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07).Conclusion:Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer. [ABSTRACT FROM AUTHOR]
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- 2013
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- View/download PDF
57. Efficacy of tamoxifen ± aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial.
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Pfeiler, G, Stöger, H, Dubsky, P, Mlineritsch, B, Singer, C, Balic, M, Fitzal, F, Moik, M, Kwasny, W, Selim, U, Renner, K, Ploner, F, Steger, G G, Seifert, M, Hofbauer, F, Sandbichler, P, Samonigg, H, Jakesz, R, Greil, R, and Fesl, C
- Abstract
Background: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial.Methods: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m(-)(2)), overweight (BMI=25-29.9 kg m(-)(2)), and obese (30 kg m(-)(2)) according to WHO criteria.Results: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients.Conclusion: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen. [ABSTRACT FROM AUTHOR]- Published
- 2013
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58. Efficacy of tamoxifen±aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial.
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Pfeiler, G, Stöger, H, Dubsky, P, Mlineritsch, B, Singer, C, Balic, M, Fitzal, F, Moik, M, Kwasny, W, Selim, U, Renner, K, Ploner, F, Steger, G G, Seifert, M, Hofbauer, F, Sandbichler, P, Samonigg, H, Jakesz, R, Greil, R, and Fesl, C
- Subjects
TAMOXIFEN ,POSTMENOPAUSE ,BREAST cancer ,BODY mass index ,AROMATASE inhibitors - Abstract
Background:There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial.Methods:ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m
− 2 ), overweight (BMI=25-29.9 kg m− 2 ), and obese (30 kg m− 2 ) according to WHO criteria.Results:Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients.Conclusion:BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen. [ABSTRACT FROM AUTHOR]- Published
- 2013
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- View/download PDF
59. A Phase l/ll Study of Quinidine, a Potential Multidrug Resistance-Reversing Agent, in Combination with Pirarubicin in Patients with Advanced Refractory Breast Cancer
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Raderer, M., primary, Depisch, D., additional, Haider, K., additional, Kwasny, W., additional, Djavanmard, M., additional, and Scheithauer, W., additional
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- 1993
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60. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the austrian breast and colorectal cancer study group.
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Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, and Filipcic L
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- 2012
61. Multisensor system for diagnosing machine tools.
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Jedrzejewski, J. and Kwasny, W.
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- 1992
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62. Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14.
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Steger GG, Galid A, Gnant M, Mlineritsch B, Lang A, Tausch C, Rudas M, Greil R, Wenzel C, Singer CF, Haid A, Pöstlberger S, Samonigg H, Luschin-Ebengreuth G, Kwasny W, Klug E, Kubista E, Menzel C, Jakesz R, and ABCSG-14
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- 2007
63. Phase II trial of pegylated liposomal doxorubicin (Caelyx) plus gemcitabine in chemotherapeutically pretreated patients with advanced breast cancer.
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Ulrich-Pur H, Kornek GV, Haider K, Kwasny W, Payrits T, Dworan N, Vormittag L, Depisch D, Lang F, and Scheithauer W
- Abstract
A phase II trial was performed to investigate the efficacy and tolerance of combined gemcitabine and liposomal doxorubicin+/-recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapeutically pretreated metastatic breast cancer. Thirty-four patients were entered in this trial. Chemotherapy consisted of gemcitabine and liposomal doxorubicin+/-G-CSF. Twenty seven patients received this regimen as 2nd line therapy, five patients as 3rd line and two patients as 4th line therapy after having failed taxane- and/or anthracycline-based chemotherapy or other drug combinations. After a median of six courses, an overall response rate of 26% (9 PR in 34 enrolled patients) was observed; 14 patients had disease stabilization (41%), and eight (24%) progressed. Three patients were not evaluable for response due to anaphylaxis after the first course and protracted thrombocytopenia. The median TTP was 7.5 months, and median overall survival was 15 months. Myelosuppression was the most frequently observed toxicity. Non-haematological side effects were generally mild to moderate. Our data suggest that gemcitabine and liposomal doxorubicin±G-CSF is an effective and fairly well tolerated regimen for chemotherapeutically pretreated patients with advanced breast cancer. [ABSTRACT FROM AUTHOR]
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- 2007
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64. Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma: results of a Phase I-II trial.
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Scheithauer, Werner, Kornek, Gabriela V., Ulrich-Pur, Herbert, Penz, Melitta, Raderer, Markus, Salek, Tomas, Haider, Karin, Kwasny, Werner, Depisch, Dieter, Scheithauer, W, Kornek, G V, Ulrich-Pur, H, Penz, M, Raderer, M, Salek, T, Haider, K, Kwasny, W, and Depisch, D
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- 2001
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65. A phase II trial of biweekly high dose gemcitabine for patients with metastatic pancreatic adenocarcinoma.
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Ulrich-Pur, Herbert, Kornek, Gabriela V., Raderer, Markus, Haider, Karin, Kwasny, Werner, Depisch, Dieter, Greul, Renate, Schneeweiss, Bruno, Krauss, Gwendolyn, Funovics, Josef, Scheithauer, Werner, Ulrich-Pur, H, Kornek, G V, Raderer, M, Haider, K, Kwasny, W, Depisch, D, Greul, R, Schneeweiss, B, and Krauss, G
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- 2000
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66. Development of Ordered Structures in the High-Temperature (HT) Cokes from Binary and Ternary Coal Blends Studied by Means of X-ray Diffraction and Raman Spectroscopy.
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Smȩdowski, Ł., Krzesinska, M., Kwasny, W., and Kozanecki, M.
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- 2011
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67. A phase I-II study of epirubicin, 5-fluorouracil, and leucovorin in advanced adenocarcinoma of the stomach.
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Kornek, Gabriela, Schulz, Franz, Depisch, Dieter, Rosen, Harald, Kwasny, Werner, Sebesta, Christian, Scheithauer, Werner, Kornek, G, Schulz, F, Depisch, D, Rosen, H, Kwasny, W, Sebesta, C, and Scheithauer, W
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- 1993
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68. Prognostic relevance of three histological grading methods in breast cancer
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Latinovic L, Heinze G, Birner P, Samonigg H, Hausmaninger H, Kubista E, Kwasny W, Michael Gnant, Jakesz R, Oberhuber G, and Austrian Breast and Colorectal Cancer Study Group
69. Overexpression of hypoxia-inducible factor 1α is associated with an unfavorable prognosis in lymph node-positive breast cancer
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Schindl, M., Sebastian F. Schoppmann, Samonigg, H., Hausmaninger, H., Kwasny, W., Gnant, M., Jakesz, R., Kubista, E., Birner, P., Oberhuber, G., Seifert, M., Agstner, I., Dadak, C., Dubsky, P., Galid, A., Gebhard, B., Hantal, E., Helbich, H., Joura, E., Kandioler-Eckersberger, D., Oberhuber, K., Ploner, M., Reiner, G., Roka, S., Rudas, M., Sam, C., Schemper, M., Schmidinger, M., Steger, G., Steiner, B., Taucher, S., Wenzl, K., Wolf, G., Mlineritsch, B., Menzel, R. -C, Hell, E., Kogelnik, H., Moritz, E., Papp, C., Schandalik, R., Umlauft, M., Waclawiczek, H., Mischinger, H. -J, Steindorfer, P., Andritsch, E., Bacher, H., Bauernhofer, T., Berger, A., Cervenka, H., El-Shabrawi, A., Freisinger, J., Hauser, H., Hebenstreit, J., Hofmann, G., Kasparek, A. -K, Konstantiniuk, P., Kosina, G., Krippl, P., Kronberger, L., Kuss, I., Luschin-Ebengreuth, G., Moser, R., Papadi, H., Pfeifer, H., Ploner, F., Reinisch, S., Riegler, M., Rosanelli, G., Schippinger, W., Schmid, M., Schwaiger, W., Smola, M., Stöger, H., Thalhammer, M., Thiel, I., Wagner, P., Wehrschütz, M., Winter, R., Zehetleitner, G., Depisch, D., Haider, K., Payrits, T., Kolb, R., Tausch, C., Aufschnaiter, M., Heck, D., Klug, R., Kugler, F., Schildberger, R., Stierer, M., Matzinger, H., Spoula, H., Renner, K., Schiessel, R., Schmidbauer, U., Wunderlich, M., Fridrik, M., Wahl, G., Bauer, D., Hofbauer, F., Lang, M., Jatzko, G., Wette, V., Starlinger, M., Urbania, A., Keller, K., Schennach, W., Zoller, H., Klug, E., Mach, K., Steflitsch, K., Berger, J., Lenzhofer, R., Winter, G., Haid, A., Koeberle, R., and Zimmermann, G.
70. Precise modelling of machine tool drives with ball screw thermal behaviour
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Winiarski, Z., Kowal, Z., Jerzy Jedrzejewski, and Kwasny, W.
71. Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer
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Schindl M, Sf, Schoppmann, Samonigg H, Hausmaninger H, Kwasny W, Michael Gnant, Jakesz R, Kubista E, Birner P, Oberhuber G, and Austrian Breast and Colorectal Cancer Study Group
72. Selected Diagnostic Methods for Machine Tools Acceptance Tests
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Jedrzejewski, J., primary, Kwasny, W., additional, Milejski, D., additional, and Szafarczyk, M., additional
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- 1985
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73. Treatment of Advanced Breast Cancer (ABC) with Docetaxel and Gemcitabine + Human Granulocyte Colony-Stimulating Factor (G-CSF).
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Kornek, G. V., Fiebiger, W., Raderer, M., Gedlicka, C., Schüll, B., Haider, K., Kwasny, W., Depisch, D., and Scheithauer, W.
- Subjects
PHARMACODYNAMICS ,CANCER chemotherapy ,BREAST cancer ,DOCETAXEL ,ANTINEOPLASTIC agents ,GRANULOCYTE-macrophage colony-stimulating factor ,DRUG efficacy ,DRUG side effects - Abstract
Background: In order to investigate the efficacy and tolerance of docetaxel in combination with gemcitabine + G-CSF in ABC we initiated a multicenter phase II trial. Methods: Fifty-two patients received a combination regimen consisting of docetaxel (50 mg/m², days 1+15) and gemcitabine (1500 mg/m², days 1+15) + G-CSF (5 mcg/kg/d, s.c.) depending on the nadir granulocyte counts. Treatment courses were repeated every 4 weeks. Results: Patients and Methods: Forty-one pts are presently evaluable for response and toxicity assessment. Twelve were pre- and 29 pts were postmenopausal. Their median age was 61 (44-75) years, and the median WHO performance status 1 (0-2). Predominant sites were visceral in 29, bone in 6 and soft-tissue in 6 pts, respectively. Eleven pts were refractory to previous 1st-line chemotherapy, all others were previously untreated. After a median of 6 (2-6) treatment courses an overall response rate of 56% including 4 CR, and 19 PR was observed. Specifically, 19/30 (63%) previously untreated pts, and 4/11 (36%) chemotherapeutically pretreated pts responded. Eleven additional pts had SD (27%) and only 7 PD (17%). The median time to response was only 2.5 (2-4.5) months. The median duration of response (>6 months), time to progression (>8 months) and survival (>13 months) with 31 pts (76%) currently alive have not been reached yet. WHO grade 3 or 4 neutropenia occurred in 6 (17%) pts each, and was complicated by septicaemia in 3 (7%). Non-hematologic side effects were generally mild to moderate, and included alopecia (68%). nausea/vomiting (63%), peripheral neuropathy (34%). tearing (31%), fatigue (47%), stomatitis (32%), peripheral edema (36%). diarrhea (24%), skin/nail reactions (36%), constipation (15%) and pathologically raised liver enzymes (27%). Conclusions: We conclude that docetaxel and gemcitabine + G-CSF is an effective and fairly well tolerated regimen for the treatment of ABC. [ABSTRACT FROM AUTHOR]
- Published
- 2001
74. Artificial Intelligence Tools in Diagnostics of Machine Tool Drives*
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Jędrzejewski, J. and Kwaśny, W.
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- 1996
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75. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial.
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Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, ABCSG (Austrian Breast and Colorectal Cancer Study Group), and GABG (German Adjuvant Breast Cancer Group)
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- 2005
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76. Clinical validation of the PAM50 risk of recurrence (ROR) score for predicting residual risk of distant-recurrence (DR) after endocrine therapy in postmenopausal women with ER+ early breast cancer (EBC): An ABCSG study.
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Gnant, M., Filipits, M., Mlineritsch, B., Dubsky, P., Jakesz, R., Kwasny, W., Fitzal, F., Rudas, M., Knauer, M., Singer, C., Greil, R., Ferree, S., Storhoff, J., Cowens, J. W., Schaper, C., Liu, S., and Nielsen, T.
- Subjects
- *
POSTMENOPAUSE , *TAMOXIFEN , *ANASTROZOLE , *GENE expression , *ANTINEOPLASTIC agents - Abstract
Aim: To assess the performance of the ROR score in predicting DR for postmenopausal patients with ER+ EBC treated with tamoxifen or tamoxifen followed by anastrozole when the PAM50 test is performed in a routine hospital pathology laboratory. Background: The multi-analyte gene-expression tests (Oncotype DX, MammaPrint) that are currently used in clinical practice to assess prognosis after endocrine therapy in primary ER+ breast cancer are performed in a central referral laboratory. PAM50 is a 50-gene test in development that is designed to be performed in local routine hospital pathology laboratories and has been optimized to separate intrinsic disease subtypes which are used to generate a ROR score. This ROR score has been clinically validated and demonstrated to contain more prognostic information than Oncotype Dx RS in the TransATAC patient population (Dowsett, SABCS, 2011). Methods: 1,251 women from the prospective randomized ABCSG-8 trial were entered into this study: the entry criteria were the availability of their FPET block and informed consent. Three unstained 10 micron sections and 1 H&E slide for each patient were sent to an independent academic pathology laboratory at BCCA where tissue review, manual micro-dissection and RNA extraction were performed. PAM50 analysis was then conducted on 250 ng of the extracted RNA using the NanoString nCounter® technology: both intrinsic subtype and ROR score were calculated. The median follow up of the patients entered into this study is 10 years. 912 are node negative and 339 are node positive. The baseline characteristics of the patients entered showed them to be a representative sample of the overall ABCSG-8 trial population. The primary analysis is designed to test whether the continuous ROR score adds prognostic value over and above the standard clinical variables, using a likelihood ratio test. Results: Results are currently being derived and will be presented in full at SABCS. Discussion: This large clinical trial serves both as a clinical validation study of the PAM 50 test and as a demonstration that a complex multi-analyte gene-expression test can be performed in a routine hospital pathology laboratory while meeting the same quality metrics as a central referral laboratory. The results of the primary analysis, when combined with the results already reported from the Trans ATAC population, yield Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC and form the basis of the design of the clinical utility studies of the PAM 50 test. [ABSTRACT FROM AUTHOR]
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- 2012
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77. Influence of Height on Risk and Outcome of Patients with Early Breast Cancer: A Pooled Analysis of 4,925 Patients from 5 Randomized Trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG).
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Gampenrieder SP, Pircher M, Fesl C, Rinnerthaler G, Mlineritsch B, Greil-Ressler S, Steger GG, Sagaster V, Fitzal F, Exner R, Devyatko Y, Balic M, Stöger H, Suppan C, Bauernhofer T, Singer CF, Pfeiler G, Seifert M, Helfgott R, Heck D, Rumpold H, Kwasny W, Wieder U, Gnant M, and Greil R
- Abstract
Background: Associations between height, cancer risk and worse outcome have been reported for several cancers including breast cancer. We hypothesized that in breast cancer clinical trials, tall women should be overrepresented and might have worse prognosis., Methods: Data of 4,935 women, included from 1990 to 2010 in 5 trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG), were analyzed retrospectively. The primary objective was to determine differences in height distribution between the ABCSG cohort and the Austrian female population according to a cross-sectional health survey conducted by the Austrian Statistic Center in 2006 and 2007. Secondary endpoints were disease-free survival (DFS) and overall survival (OS) in different height classes and differences of body mass index (BMI) distribution., Results: Breast cancer patients in the ABCSG cohort were only slightly but statistically significantly smaller compared to unselected Austrian adult females (mean 164.3 vs. 164.8 cm; p < 0.0001) and significantly more patients were seen in the lower body height class (50 vs. 46%; p < 0.0001) when using the median as a cutoff. However, after adjustment for age, the difference in body height between the two cohorts was no longer significant ( p = 0.089). DFS and OS in the two upper height groups (≥170 cm) compared to the two lowest height groups (<160 cm) was not significantly different (5-year DFS: 84.7 vs. 83.0%; HR 0.91, 95% CI 0.73-1.13, p = 0.379; 5-year OS: 94.8 vs. 91.7%; HR 0.74, 95% CI 0.55-1.00, p = 0.051). The BMI of ABCSG patients was significantly higher than in the reference population (mean BMI 24.64 vs. 23.96; p < 0.0001)., Conclusions: Our results do not confirm previous findings that greater body height is associated with a higher breast cancer risk and worse outcome., Competing Interests: Verena Sagaster declares the following relations: Employment: none; Leadership: none; Stock or other Ownership: none; Honoraria: none; Consulting or Advisory Role: Bayer, Novartis, Eli Lilly; Speakers Bureau: none; Research Funding: none; Patents, Royalties, Other Intellectual Property: none; Expert Testimony: none; Travel, Accommodation, Expenses: none; Other Relationships: none. Florian Fitzal declares the following relations: Employment: none; Leadership: none; Stock or other Ownership: none; Honoraria: none; Consulting or Advisory Role: Pfizer, Roche; Speakers Bureau: none; Research Funding: Novartis, Pfizer, Roche, AstraZeneca, Comesa, Bondimed, Nanostring; Patents, Royalties, Other Intellectual Property: none; Expert Testimony: none; Travel, Accommodation, Expenses: Novartis, Pfizer, Roche, AstraZeneca, Comesa, Bondimed, Nanostring; Other Relationships: none. Yelena Devyatko declares the following relations: Employment: none; Leadership: none; Stock or other Ownership: none; Honoraria: none; Consulting or Advisory Role: none; Speakers Bureau: none; Research Funding: none; Patents, Royalties, Other Intellectual Property: none; Expert Testimony: none; Travel, Accommodation, Expenses: Roche; Other Relationships: none. Georg Pfeiler declares the following relations: Employment: none; Leadership: none; Stock or other Ownership: none; Honoraria: Amgen, Lilly, Roche, AstraZeneca, Novartis, Accord, Pfizer; Consulting or Advisory Role: Amgen, Lilly, Roche, AstraZeneca, Novartis, Accord, Pfizer; Speakers Bureau: none; Research Funding: none; Patents, Royalties, Other Intellectual Property: none; Expert Testimony: none; Travel, Accommodation, Expenses: none; Other Relationships: none. Michael Gnant declares the following relations: Employment: Snadoz; Leadership: none; Stock or other Ownership: none; Honoraria: Amgen, AstraZeneca, Celgene, Eli Lilly, Invectys, Pfizer, Nansotring, Novartis, Roche, Medison; Consulting or Advisory Role: AstraZeneca, Eli Lilly; Speakers Bureau: none; Research Funding: none; Patents, Royalties, Other Intellectual Property: none; Expert Testimony: none; Travel, Accommodation, Expenses: Amgen, AstraZeneca, Eli Lilly, Ipsen, Pfizer, Roche, Medison; Other Relationships: none. All other authors declare that they do not have any conflicts of interest in direct or indirect relationship with this research., (Copyright © 2021 by S. Karger AG, Basel.)
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- 2022
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78. Predictive Value of Molecular Subtypes in Premenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the ABCSG Trial 5.
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Bago-Horvath Z, Rudas M, Singer CF, Greil R, Balic M, Lax SF, Kwasny W, Hulla W, Gnant M, and Filipits M
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- Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms classification, Breast Neoplasms genetics, Breast Neoplasms pathology, Chemotherapy, Adjuvant adverse effects, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease-Free Survival, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Goserelin administration & dosage, Goserelin adverse effects, Humans, Methotrexate administration & dosage, Methotrexate adverse effects, Middle Aged, Neoplasm Recurrence, Local classification, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Premenopause drug effects, Premenopause genetics, Progression-Free Survival, Receptors, Estrogen genetics, Receptors, Progesterone genetics, Tamoxifen adverse effects, Breast Neoplasms drug therapy, Ki-67 Antigen genetics, Neoplasm Recurrence, Local drug therapy, Receptor, ErbB-2 genetics, Tamoxifen administration & dosage
- Abstract
Purpose: To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor-positive early breast cancer who received adjuvant endocrine treatment or chemotherapy., Experimental Design: Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors., Results: 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41-3.49; P = 0.001] and OS (adjusted HR for death: 3.51; 95% CI, 1.80-6.87; P < 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS)., Conclusions: Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF. See related commentary by Hunter et al., p. 5543 ., (©2020 American Association for Cancer Research.)
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- 2020
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79. Endocrine therapy with or without whole breast irradiation in low-risk breast cancer patients after breast-conserving surgery: 10-year results of the Austrian Breast and Colorectal Cancer Study Group 8A trial.
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Fastner G, Sedlmayer F, Widder J, Metz M, Geinitz H, Kapp K, Fesl C, Sölkner L, Greil R, Jakesz R, Kwasny W, Heck D, Bjelic-Radisic V, Balic M, Stöger H, Wieder U, Zwrtek R, Semmler D, Horvath W, Melbinger-Zeinitzer E, Wiesholzer M, Wette V, and Gnant M
- Subjects
- Aged, Breast Neoplasms pathology, Breast Neoplasms radiotherapy, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local radiotherapy, Prognosis, Survival Rate, Antineoplastic Agents, Hormonal therapeutic use, Brachytherapy mortality, Breast Neoplasms drug therapy, Mastectomy, Segmental mortality, Neoplasm Recurrence, Local drug therapy
- Abstract
Purpose: To investigate long-term results of patients with hormonal receptor-positive breast cancer treated with breast-conserving surgery (BCS) and consecutive endocrine therapy (ET) with or without whole breast irradiation (WBI)., Methods and Materials: Within the 8 A trial of the Austrian Breast and Colorectal Cancer Study Group, a total of 869 patients received ET after BCS which was randomly followed by WBI (n = 439, group 1) or observation (n = 430, group 2). WBI was applied up to a mean total dosage of 50 Gy (+/- 10 Gy boost) in conventional fractionation., Results: After a median follow-up of 9.89 years, 10 in-breast recurrences (IBRs) were observed in group 1 and 31 in group 2, resulting in a 10-year local recurrence-free survival (LRFS) of 97.5% and 92.4%, respectively (p = 0.004). This translated into significantly higher rates for disease-free survival (DFS): 94.5% group 1 vs 88.4% group 2, p = 0.0156. For distant metastases-free survival (DMFS) and overall survival (OS), respective 10-year rates amounted 96.7% and 86.6% for group 1 versus 96.4% and 87.6%, for group 2 (ns). WBI (hazard ratio [HR]: 0.27, p < 0.01) and tumour grading (HR: 3.76, p = 0.03) were found as significant predictors for IBR in multiple cox regression analysis., Conclusions: After a median follow-up of 10 years, WBI resulted in a better local control and DFS compared with ET alone. The omission of WBI and tumour grading, respectively, were the only negative predictors for LRFS., Competing Interests: Conflict of interest statement F.S. reports a research collaboration with Elekta, during the conduct of the study. R.G. has received honoraria, has been a consultant or has served an advisory role, has received research funding and has received travel and accommodations expenses from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, Abbvie, Gilead, Daiichi Sankyo, and Janssen. G.M. has received institutional research support from AstraZeneca, Roche, Novartis, and Pfizer and has received lecture fees, honoraria for participation on advisory boards, and travel support from Amgen, AstraZeneca, Celgene, EliLilly, Invectys, Pfizer, Nanostring, Novartis, Roche, and Medison. He has served as a consultant for AstraZeneca and EliLilly and an immediate family member is employed by Sandoz. The other authors report no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2020
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80. Prognostic value of number of removed lymph nodes, number of involved lymph nodes, and lymph node ratio in 7502 breast cancer patients enrolled onto trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG).
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Tausch C, Taucher S, Dubsky P, Seifert M, Reitsamer R, Kwasny W, Jakesz R, Fitzal F, Filipcic L, Fridrik M, Greil R, and Gnant M
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- Breast Neoplasms mortality, Breast Neoplasms therapy, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Middle Aged, Multivariate Analysis, Neoplasm Grading, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local therapy, Neoplasm Staging, Prognosis, Prospective Studies, Retrospective Studies, Survival Rate, Breast Neoplasms pathology, Lymph Nodes pathology, Neoplasm Recurrence, Local pathology
- Abstract
Purpose: The number of removed axillary lymph nodes and the ratio of involved to removed lymph nodes are described as independent prognostic factors beside the absolute number of involved lymph nodes in breast cancer patients. The correlation between these factors and prognosis were investigated in trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)., Methods: This retrospective analysis is based on the data of 7052 patients with endocrine-responsive breast cancer who were randomized in four trials of the ABCSG in the years 1990-2006 and underwent axillary lymph node dissection. The prognostic value of number of removed nodes (NRN), number of involved nodes (NIN), and ratio of involved to removed nodes (lymph node ratio, LNR) concerning recurrence-free survival and overall survival was analyzed., Results: A total of 2718 patients had node-positive disease. No correlation was found between NRN and prognosis. Increasing NIN and LNR were significantly associated with worse recurrence-free survival and overall survival in univariate and multivariate analyses (P < .001). Only in the subgroup of patients with one to three positive lymph nodes and treated with mastectomy (n = 728) was LNR an additional prognostic factor in univariate and multivariate analyses., Conclusions: For breast cancer patients stringently medicated in the framework of prospective adjuvant clinical trials and requiring a mandatory minimum of removed nodes, NRN does not influence prognosis, and LNR is not superior to NIN as prognostic factor. In patients with one to three positive lymph nodes and mastectomy, LNR could play a role as an additional prognostic factor.
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- 2012
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81. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial.
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Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, Jakesz R, Seifert M, Hubalek M, Pristauz G, Bauernhofer T, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Hochreiner G, Forsthuber EP, Fesl C, and Greil R
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- Adult, Anastrozole, Antineoplastic Agents, Hormonal therapeutic use, Bone Density Conservation Agents therapeutic use, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Staging, Nitriles therapeutic use, Premenopause, Tamoxifen therapeutic use, Treatment Outcome, Triazoles therapeutic use, Zoledronic Acid, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Diphosphonates therapeutic use, Imidazoles therapeutic use
- Abstract
Background: Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid., Methods: ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I-II) breast cancer receiving goserelin (3.6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing., Findings: At a median follow-up of 62 months (range 0-114.4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid reduced risk of disease-free survival events overall (HR 0.68, 95% CI 0.51-0.91; p=0.009), although the difference was not significant in the tamoxifen (HR 0.67, 95% CI 0.44-1.03; p=0.067) and anastrozole arms (HR 0.68, 95% CI 0.45-1.02; p=0.061) assessed separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without; HR 0.67, 95% CI 0.41-1.07; p=0.09). There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone (HR 1.08, 95% CI 0.81-1.44; p=0.591), but overall survival was worse with anastrozole than with tamoxifen (46 vs 27 deaths; HR 1.75, 95% CI 1.08-2.83; p=0.02). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was reported in 601 patients (33%; 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%; 192 vs 169), headache in 280 (16%; 147 vs 133), and arthralgia in 266 (15%; 145 vs 121)., Interpretation: Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen. There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer., Funding: AstraZeneca; Novartis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
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- 2011
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82. Low p27 expression predicts early relapse and death in postmenopausal hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy.
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Filipits M, Rudas M, Heinzl H, Jakesz R, Kubista E, Lax S, Schippinger W, Dietze O, Greil R, Stiglbauer W, Kwasny W, Nader A, Stierer M, and Gnant MF
- Subjects
- Aged, Antineoplastic Agents, Hormonal administration & dosage, Breast Neoplasms mortality, Breast Neoplasms surgery, Chemotherapy, Adjuvant, Female, Follow-Up Studies, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Prognosis, Receptors, Progesterone genetics, Recurrence, Survival Analysis, Survival Rate, Tamoxifen administration & dosage, Treatment Outcome, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms diagnosis, Breast Neoplasms drug therapy, Cyclin-Dependent Kinase Inhibitor p27 biosynthesis, Postmenopause, Receptors, Progesterone analysis, Tamoxifen therapeutic use
- Abstract
Purpose: Previously, we have shown that p27 may be a potential predictive biomarker for the selection of premenopausal women with early-stage hormone-responsive breast cancer for adjuvant endocrine therapy. The purpose of the present study was to assess the clinical relevance of p27 expression in postmenopausal hormone receptor-positive breast cancer patients who were treated with adjuvant tamoxifen therapy., Experimental Design: We determined the expression of p27 by immunohistochemistry in the surgical specimens of breast carcinoma patients who had been enrolled in Austrian Breast and Colorectal Cancer Study Group Trial 06 and received tamoxifen for 5 years. Early relapse and death within the first 5 years of follow-up were analyzed using Cox models adjusted for clinical and pathologic factors., Results: p27 expression was high (>70% p27-positive tumor cells) in 252 of 483 (52%) tumor specimens and was associated with favorable outcome of the patients. Women with high p27 expression had a significantly longer disease-free survival (adjusted hazard ratio for relapse, 0.22; 95% confidence interval, 0.11-0.42; P < 0.001) and overall survival (adjusted hazard ratio for death, 0.39; 95% confidence interval, 0.21-0.72; P = 0.002) as compared with women with low p27 expression., Conclusion: Low p27 expression independently predicts early relapse and death in postmenopausal women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen for 5 years.
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- 2009
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83. Endocrine therapy plus zoledronic acid in premenopausal breast cancer.
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Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rücklinger E, Greil R, and Marth C
- Subjects
- Adult, Anastrozole, Antineoplastic Agents, Hormonal adverse effects, Aromatase Inhibitors adverse effects, Aromatase Inhibitors therapeutic use, Bone Density Conservation Agents adverse effects, Breast Neoplasms surgery, Chemotherapy, Adjuvant, Diphosphonates adverse effects, Disease-Free Survival, Drug Therapy, Combination, Estrogen Antagonists adverse effects, Estrogen Antagonists therapeutic use, Female, Follow-Up Studies, Humans, Imidazoles adverse effects, Middle Aged, Nitriles adverse effects, Nitriles therapeutic use, Receptors, Estrogen analysis, Tamoxifen adverse effects, Tamoxifen therapeutic use, Triazoles adverse effects, Triazoles therapeutic use, Zoledronic Acid, Antineoplastic Agents, Hormonal therapeutic use, Bone Density Conservation Agents therapeutic use, Breast Neoplasms drug therapy, Diphosphonates therapeutic use, Goserelin therapeutic use, Imidazoles therapeutic use, Premenopause
- Abstract
Background: Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties., Methods: We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points., Results: After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles., Conclusions: The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646.), (2009 Massachusetts Medical Society)
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- 2009
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84. The potential risk of neoadjuvant chemotherapy in breast cancer patients--results from a prospective randomized trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-07).
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Taucher S, Steger GG, Jakesz R, Tausch C, Wette V, Schippinger W, Kwasny W, Reiner G, Greil R, Dubsky P, Poestlberger S, Tschmelitsch J, Samonigg H, and Gnant M
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms pathology, Cyclophosphamide administration & dosage, Disease-Free Survival, Female, Fluorouracil administration & dosage, Humans, Medical Oncology methods, Methotrexate administration & dosage, Middle Aged, Prospective Studies, Risk, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Chemotherapy, Adjuvant methods, Colorectal Neoplasms metabolism
- Abstract
Purpose: To evaluate the impact that pre- and postoperatively administered chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF) and postoperative chemotherapy vs. postoperative chemotherapy alone have on long-term prognosis., Patients and Methods: The ABCSG conducted a nationwide randomized phase III trial in high-risk endocrine non-responsive breast cancer patients comparing pre- and postoperative chemotherapy containing CMF as preoperative treatment vs. postoperative chemotherapy alone between 1991 and 1999. From 1996 the ABCSG-07 protocol was amended to also allow randomization of high-risk endocrine-responsive patients. Of 423 eligible patients with high-risk primary breast cancer, 203 patients were randomly assigned to preoperatively receive three cycles of CMF (cyclophosphamide, methotrexate, fluorouracil; 600/40/600 mg/m(2)) intravenously on day 1 and 8, while 195 patients received postoperative chemotherapy alone. In both groups, three cycles of CMF were given initially, and another three cycles of CMF were administered in node-negative patients, whereas node-positive patients received three cycles of EC (epirubicin, cyclophosphamide; 70/600 mg/m(2))., Results: Overall response rate to preoperative chemotherapy with three cycles of CMF was 56.2%; complete pathological response was achieved in 12 patients (5.9%). Recurrence-free survival was significantly better in patients receiving chemotherapy postoperatively (HR 0.7, 0.515-0.955; P = 0.024). No survival difference was observed between the two therapy groups (HR 0.800, 0.563-1.136; P = 0.213)., Discussion: Preoperative chemotherapy with CMF has to be considered as insufficient in high-risk breast cancer patients. Delayed surgery and anthracycline-based chemotherapy result in shorter recurrence-free survival but not overall survival.
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- 2008
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85. Anemia is a significant prognostic factor in local relapse-free survival of premenopausal primary breast cancer patients receiving adjuvant cyclophosphamide/methotrexate/5-fluorouracil chemotherapy.
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Dubsky P, Sevelda P, Jakesz R, Hausmaninger H, Samonigg H, Seifert M, Denison U, Mlineritsch B, Steger G, Kwasny W, Stöger H, Bartsch R, Stierer M, Taucher S, Fridrik M, Schippinger W, Greil R, Pötter R, and Gnant M
- Subjects
- Adult, Anemia epidemiology, Breast Neoplasms drug therapy, Chemotherapy, Adjuvant, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease-Free Survival, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Humans, Kaplan-Meier Estimate, Methotrexate administration & dosage, Methotrexate adverse effects, Premenopause, Prognosis, Radiotherapy, Anemia complications, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms complications, Breast Neoplasms mortality
- Abstract
Purpose: To determine the effects of anemia on local relapse-free, relapse-free, and overall survival (LRFS, RFS, and OS, respectively) in premenopausal, primary breast cancer patients receiving adjuvant polychemotherapy, and to determine which conventional prognostic factors affected these outcomes., Experimental Design: Four hundred twenty-four premenopausal patients with early-stage primary breast cancer and hormone receptor-expressing tumors were treated with i.v. cyclophosphamide/methotrexate/5-fluorouracil (CMF) polychemotherapy as part of an adjuvant phase III trial (Austrian Breast and Colorectal Cancer Study Group Trial 5). The influence of anemia (hemoglobin <12 g/dL) on LRFS, RFS, and OS was evaluated in a retrospective analysis., Results: Of 424 patients, 77 (18.2%) developed anemia on CMF chemotherapy. After a median follow-up time of 5 years, 8.9% of nonanemic patients had local relapse compared with 19.6% of anemic patients (P=0.0006). Although mastectomy was associated with anemia (26% versus 13.7% in breast conserving surgery; P=0.002), multivariate analysis did not show mastectomy per se to be a significant risk factor for LRFS. Age, lymph node status, and hemoglobin had an independent significant influence on LRFS (P<0.005). Anemic patients had a relative risk of 2.96 (95% confidence interval, 1.41-6.23) for developing local relapse in comparison with nonanemic patients., Conclusion: Premenopausal breast cancer patients who developed anemia during the CMF regimen had significantly worse LRFS. In Austrian Breast and Colorectal Cancer Study Group Trial 5, anemia may have contributed to an almost doubled incidence of local recurrence in the chemotherapy arm. Molecular targets associated with tumor hypoxia and distinct from erythropoiesis should receive further attention in experimental and clinical settings.
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- 2008
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86. Cyclin D1 expression in breast cancer patients receiving adjuvant tamoxifen-based therapy.
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Rudas M, Lehnert M, Huynh A, Jakesz R, Singer C, Lax S, Schippinger W, Dietze O, Greil R, Stiglbauer W, Kwasny W, Grill R, Stierer M, Gnant MF, and Filipits M
- Subjects
- Adult, Aged, Aged, 80 and over, Aminoglutethimide administration & dosage, Breast Neoplasms diagnosis, Chemotherapy, Adjuvant, Cyclophosphamide administration & dosage, Disease-Free Survival, Female, Fluorouracil administration & dosage, Follow-Up Studies, Goserelin administration & dosage, Humans, Methotrexate administration & dosage, Middle Aged, Prognosis, Receptors, Cytoplasmic and Nuclear metabolism, Recurrence, Tamoxifen administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Cyclin D1 metabolism, Tamoxifen therapeutic use
- Abstract
Purpose: The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor-positive breast cancer patients who were treated with tamoxifen-based therapy., Experimental Design: We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors., Results: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1-positive tumors compared with patients with cyclin D1-negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1-positive tumors than in patients with cyclin D1-negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005]., Conclusion: Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen-based therapy.
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- 2008
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87. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a.
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Jakesz R, Greil R, Gnant M, Schmid M, Kwasny W, Kubista E, Mlineritsch B, Tausch C, Stierer M, Hofbauer F, Renner K, Dadak C, Rücklinger E, and Samonigg H
- Subjects
- Aged, Aged, 80 and over, Aminoglutethimide therapeutic use, Anastrozole, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal adverse effects, Aromatase Inhibitors administration & dosage, Aromatase Inhibitors adverse effects, Austria, Breast Neoplasms chemistry, Breast Neoplasms pathology, Breast Neoplasms prevention & control, Breast Neoplasms surgery, Chemotherapy, Adjuvant, Disease-Free Survival, Drug Administration Schedule, Female, Humans, Kaplan-Meier Estimate, Logistic Models, Lymphatic Metastasis, Male, Middle Aged, Nitriles administration & dosage, Nitriles adverse effects, Odds Ratio, Proportional Hazards Models, Prospective Studies, Receptors, Estrogen analysis, Receptors, Progesterone analysis, Research Design, Tamoxifen therapeutic use, Treatment Outcome, Triazoles administration & dosage, Triazoles adverse effects, Antineoplastic Agents, Hormonal therapeutic use, Aromatase Inhibitors therapeutic use, Breast Neoplasms drug therapy, Nitriles therapeutic use, Postmenopause, Triazoles therapeutic use
- Abstract
Background: Clinical trial data have shown that among breast cancer patients who were disease free after 5 years of adjuvant treatment with tamoxifen, further extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces breast cancer recurrence. We examined the efficacy and tolerability of extended adjuvant therapy with another aromatase inhibitor, anastrozole, for 3 years among women who had completed 5 years of adjuvant therapy., Methods: Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6a is an extension of ABCSG Trial 6, in which hormone receptor-positive postmenopausal patients received 5 years of adjuvant tamoxifen, with or without the aromatase inhibitor aminoglutethimide, for the first 2 years of therapy. For ABCSG Trial 6a, patients who were disease free at the end of Trial 6 were randomly assigned to receive either 3 years of anastrozole or no further treatment. Efficacy data were analyzed with the use of a Cox proportional hazards regression model with two-sided P values and Kaplan-Meier curves, and tolerability data were estimated using logistic regression analysis with odds ratios and 95% confidence intervals (CIs)., Results: ABCSG Trial 6a included 856 patients. At a median follow-up of 62.3 months, women who received anastrozole (n = 387) had a statistically significantly reduced risk of recurrence (locoregional recurrence, contralateral breast cancer, or distant metastasis) compared with women who received no further treatment (n = 469; hazard ratio = 0.62; 95% CI = 0.40 to 0.96, P = .031). Anastrozole was well tolerated, and no unexpected adverse events were reported., Conclusions: These data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years with anastrozole compared with no further treatment. Further research is required to define the optimum length of extended adjuvant therapy and to investigate the possibility of tailoring this period to suit different disease types.
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- 2007
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88. Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer.
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Pötter R, Gnant M, Kwasny W, Tausch C, Handl-Zeller L, Pakisch B, Taucher S, Hammer J, Luschin-Ebengreuth G, Schmid M, Sedlmayer F, Stierer M, Reiner G, Kapp K, Hofbauer F, Rottenfusser A, Pöstlberger S, Haider K, Draxler W, and Jakesz R
- Subjects
- Aged, Aged, 80 and over, Anastrozole, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Prospective Studies, Radiotherapy Dosage, Survival Rate, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Mastectomy, Segmental, Nitriles therapeutic use, Tamoxifen therapeutic use, Triazoles therapeutic use
- Abstract
Purpose: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial., Methods and Material: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy +/- boost (n = 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months., Results: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival., Conclusion: Breast radiotherapy +/- boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse.
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- 2007
- Full Text
- View/download PDF
89. Impact of pretreatment thrombocytosis on survival in primary breast cancer.
- Author
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Taucher S, Salat A, Gnant M, Kwasny W, Mlineritsch B, Menzel RC, Schmid M, Smola MG, Stierer M, Tausch C, Galid A, Steger G, and Jakesz R
- Subjects
- Aged, Breast Neoplasms pathology, Female, Humans, Middle Aged, Multivariate Analysis, Neoplasm Metastasis, Platelet Count, Prognosis, Retrospective Studies, Risk Factors, Survival Analysis, Survival Rate, Thrombocytosis etiology, Breast Neoplasms complications, Breast Neoplasms mortality, Thrombocytosis mortality
- Abstract
Platelet count has been reported to have predictive value in various cancer entities. In the case of breast cancer, evidence about involvement of platelets is still incomplete. Our objective was to assess the influence of pretreatment thrombocytosis on survival and establish its prognostic relevance for breast cancer patients. We performed a retrospective, multivariate analysis of 4,300 patients with early-stage breast cancer. All subjects participated in one of five prospective, randomized, multicenter trials conducted by the Austrian Breast and Colorectal Cancer Study Group. Thrombocytosis was defined as a platelet count exceeding 400 G/L. Median follow-up was 52 months. Univariate and multiple Cox regression models were calculated for overall survival (OS), breast cancer-related survival and disease-free survival (DFS). Pretreatment thrombocytosis was observed in 161 patients (3.7%). Estimated median OS, breast cancer-related survival and DFS for patients with versus those without thrombocytosis was 71.0 versus 99.5, 72.0 versus 100.9, and 80.4 versus 88.4 months, respectively (p = 0.0054, p = 0.0095, p = 0.0199). A multiple Cox regression model including tumor and nodal status, grading, age, hormone receptor status and pretreatment thrombocytosis identified pretreatment thrombocytosis as an independent predictive factor for OS (p = 0.0064) and breast cancer-related survival (p = 0.0162). Multivariate analysis failed to identify pretreatment thrombocytosis as an independent risk factor for DFS (p = 0.1355). In our retrospective study, elevated platelet counts at time of diagnosis were associated with poor prognosis in breast cancer. We hypothesize that platelets may contribute to the pathophysiology of hematogenous metastasis.
- Published
- 2003
90. Significant increase in breast conservation in 16 years of trials conducted by the Austrian Breast & Colorectal Cancer Study Group.
- Author
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Jakesz R, Samonigg H, Gnant M, Kubista E, Depisch D, Kolb R, Mlineritsch B, Mischinger HJ, Menzel RC, Steindorfer P, Kwasny W, Tausch C, Stierer M, Taucher S, Seifert M, and Hausmaninger H
- Subjects
- Aged, Aged, 80 and over, Austria, Clinical Trials as Topic, Female, Humans, Lymphatic Metastasis, Middle Aged, Postmenopause, Premenopause, Time Factors, Breast Neoplasms surgery, Mastectomy methods, Mastectomy statistics & numerical data
- Abstract
Objective: To confirm evidence that breast-conserving treatment (BCT) does not impair the prognosis in breast cancer patients as compared to mastectomy and to argue that it be regarded as the treatment of choice in stage I and II disease., Summary Background Data: Scientifically, survival rates in breast cancer have been shown to be stage-dependent, but independent of the extent of surgical breast tissue removal, as long as the resection margins are free of tumor infiltration., Methods: Between 1984 and 1997, six different trials conducted by the Austrian Breast & Colorectal Cancer Study Group accrued a total of 4,259 women with hormone-responsive disease. The authors selected and compared three patient groups (n = 3,316) according to pathologic stage, age, and the surgical procedure applied., Results: Over this interval, the BCT rate in the premenopausal node-positive subgroup experienced a highly significant increase from 27.2% to 73.2% overall. In the group of postmenopausal node-negative patients, the BCT rate grew significantly by 37.3% to 77.3% in total. With an overall BCT rate growing from 22.5% to 56.8% in postmenopausal node-positive women, those presenting with T1 tumors saw a significant increase from 35.1% to 65.9%. Mortality and local recurrence rates proved stable or even decreased considerably over time and in all subgroups., Conclusions: The presented outcome of BCT rates, significantly improved over this 16-year period and in no way counterbalanced by higher local recurrence or death rates, reflects an excellent example of surgical quality control. BCT can safely be regarded as the standard of therapy for T1 and increasingly for T2 disease. Especially in multi-institutional adjuvant breast cancer trials, the highest priority should be given to breast-conserving procedures.
- Published
- 2003
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91. Randomized trial of tamoxifen versus tamoxifen plus aminoglutethimide as adjuvant treatment in postmenopausal breast cancer patients with hormone receptor-positive disease: Austrian breast and colorectal cancer study group trial 6.
- Author
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Schmid M, Jakesz R, Samonigg H, Kubista E, Gnant M, Menzel C, Seifert M, Haider K, Taucher S, Mlineritsch B, Steindorfer P, Kwasny W, Stierer M, Tausch C, Fridrik M, Wette V, Steger G, and Hausmaninger H
- Subjects
- Aged, Aminoglutethimide administration & dosage, Aminoglutethimide adverse effects, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Austria, Breast Neoplasms chemistry, Chemotherapy, Adjuvant, Disease Progression, Drug Administration Schedule, Estrogen Receptor Modulators administration & dosage, Estrogen Receptor Modulators adverse effects, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Neoplasms, Second Primary etiology, Receptors, Estrogen analysis, Receptors, Progesterone analysis, Survival Analysis, Tamoxifen administration & dosage, Tamoxifen adverse effects, Treatment Outcome, Aminoglutethimide therapeutic use, Antineoplastic Agents, Hormonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Estrogen Receptor Modulators therapeutic use, Postmenopause, Tamoxifen therapeutic use
- Abstract
Purpose: To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor-positive, early-stage breast cancer., Patients and Methods: A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years., Results: All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P =.89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P =.74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P =.0001)., Conclusion: Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.
- Published
- 2003
- Full Text
- View/download PDF
92. Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.
- Author
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Jakesz R, Hausmaninger H, Kubista E, Gnant M, Menzel C, Bauernhofer T, Seifert M, Haider K, Mlineritsch B, Steindorfer P, Kwasny W, Fridrik M, Steger G, Wette V, and Samonigg H
- Subjects
- Breast Neoplasms mortality, Chemotherapy, Adjuvant, Female, Humans, Neoplasm Recurrence, Local, Ovariectomy, Survival Rate, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms therapy, Cyclophosphamide therapeutic use, Fluorouracil therapeutic use, Goserelin administration & dosage, Methotrexate therapeutic use, Premenopause, Tamoxifen administration & dosage
- Abstract
Purpose: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy., Patients and Methods: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death., Results: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195)., Conclusion: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.
- Published
- 2002
- Full Text
- View/download PDF
93. Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer.
- Author
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Schindl M, Schoppmann SF, Samonigg H, Hausmaninger H, Kwasny W, Gnant M, Jakesz R, Kubista E, Birner P, and Oberhuber G
- Subjects
- Disease-Free Survival, Female, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Immunoenzyme Techniques, Lymph Nodes pathology, Lymphatic Metastasis, Microscopy, Confocal, Middle Aged, Neoplasm Invasiveness pathology, Prognosis, Prospective Studies, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, Survival Rate, Tumor Suppressor Protein p53 metabolism, Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Transcription Factors metabolism
- Abstract
Purpose: Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and is involved in various pathways supporting tumor growth and progression. The aim of this study was to determine the prognostic influence of HIF-1alpha expression in patients with advanced-stage breast cancer, evident by positive lymph nodes., Experimental Design: Expression of HIF-1alpha was determined immunohistochemically in 206 patients with lymph node-positive breast cancer. Furthermore, the interrelationship of HIF-1alpha with p53 and HER-2 protein expression, estrogen receptor density, and survival was analyzed. Colocalization of p53 and HIF-1alpha proteins was analyzed by confocal laser scanning microscopy., Results: Strong nuclear expression of HIF-1alpha by invasive cancer cells was found in 48 patients (23.3%), moderate expression was found in 74 patients (35.9%), and weak expression was found in 35 patients (17%); no expression was observed in 49 patients (23.8%). HIF-1alpha protein overexpression was associated with significantly shorter overall and disease-free survival time (P = 0.003 and P = 0.001, respectively; Cox regression analysis). No correlation of HIF-1alpha and HER-2 expression or estrogen receptor density was observed., Conclusions: This study shows that HIF-1alpha is an independent prognostic factor for an unfavorable prognosis in patients with lymph node-positive breast cancer. Our results indicate that patients with advanced-stage breast cancers might profit from future therapies targeting HIF-1alpha.
- Published
- 2002
94. Treatment of advanced breast cancer with docetaxel and gemcitabine with and without human granulocyte colony-stimulating factor.
- Author
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Kornek GV, Haider K, Kwasny W, Raderer M, Schüll B, Payrits T, Depisch D, Kovats E, Lang F, and Scheithauer W
- Subjects
- Adult, Aged, Anemia chemically induced, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms pathology, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Docetaxel, Fatigue chemically induced, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte Colony-Stimulating Factor adverse effects, Humans, Leukopenia chemically induced, Middle Aged, Nausea chemically induced, Nervous System Diseases chemically induced, Paclitaxel administration & dosage, Paclitaxel adverse effects, Survival Analysis, Treatment Outcome, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Deoxycytidine analogs & derivatives, Paclitaxel analogs & derivatives, Taxoids
- Abstract
Purpose: A multicenter Phase II trial was performed to investigate the efficacy and tolerance of combined docetaxel and gemcitabine +/- recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with metastatic breast cancer., Patients and Methods: Fifty-two patients participated in this trial, 51 of whom are evaluable for response. Thirty-eight patients received this combination as first-line chemotherapy, and 14 patients received this combination as second-line chemotherapy, including 10 patients who had failed anthracyclines. Therapy consisted of 1500 mg/m2 gemcitabine and 50 mg/m2 docetaxel, both administered on days 1 and 15 every 4 weeks. Depending on the absolute neutrophil counts on the day of scheduled chemotherapeutic drug administration, a 5-day course of 5 microg/kg G-CSF was given., Results: The overall response rate was 60.5% (95% confidence interval, 43.4-75.9%) in patients receiving docetaxel plus gemcitabine as first-line chemotherapy, including 4 complete responses (10.5%) and 19 partial remissions (50%); 9 patients (24%) had disease stabilization, and only 5 (13%) progressed. Second-line treatment with this regimen resulted in 6 of 14 (43%) objective responses, 5 had stable disease, and 3 progressive disease. The median time to progression was 8.5 months in the first-line setting and 6.6 months in the second-line setting, respectively. After a median follow-up time of 15 months, 36 patients (69%) are still alive with metastatic disease. Myelosuppression was commonly observed; WHO grade 3 or 4 neutropenia, however, occurred in only 15 (29%) patients and was complicated by septicemia in 2 cases; grade 3 anemia was seen in 1 patient (2%). Severe (grade 3) nonhematological toxicity except for alopecia was rarely observed and included nausea/vomiting in 3 (6%), stomatitis in 2 (4%), anaphylaxis in 2, and peripheral neuropathy, skin toxicity, and increase of liver enzymes each in one patient., Conclusion: Our data suggest that docetaxel and gemcitabine with and without G-CSF is an effective and fairly well-tolerated regimen for the treatment of advanced breast cancer. It might be particularly useful in patients exposed previously to adjuvant or palliative anthracyclines and/or alkylating agents.
- Published
- 2002
95. [Early experience with the advanced breast biopsy instrumentation system in a multicentre study].
- Author
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Kwasny W, Tausch C, Haid A, Stierer M, Konstantiniuk P, Wayand U, and Sevelda P
- Subjects
- Austria, Breast pathology, Breast Neoplasms mortality, Breast Neoplasms surgery, Carcinoma, Ductal, Breast mortality, Carcinoma, Ductal, Breast surgery, Carcinoma, Intraductal, Noninfiltrating mortality, Carcinoma, Intraductal, Noninfiltrating surgery, Female, Follow-Up Studies, Humans, Mastectomy, Segmental instrumentation, Middle Aged, Sensitivity and Specificity, Survival Rate, Biopsy instrumentation, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Carcinoma, Intraductal, Noninfiltrating pathology, Mammography instrumentation
- Abstract
Early Experience with the Advanced Breast Biopsy Instrumentation System in a Multicentre Study In an Austrian multicentre trial between September 1998 and December 2001, 474 procedures were performed with the Advanced Breast Biopsy Instrumentation (ABBI), and 389 were entered in the protocol. For reasons of patient comfort, radiological accuracy and low complication rate, the stereotactic excision biopsy with the ABBI system is a useful alternative to 'open' biopsy of non-palpable breast lesions, although there are technical limitations. The question of the therapeutic option in breast cancer cannot be answered yet.
- Published
- 2002
- Full Text
- View/download PDF
96. Prognostic relevance of three histological grading methods in breast cancer.
- Author
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Latinovic L, Heinze G, Birner P, Samonigg H, Hausmaninger H, Kubista E, Kwasny W, Gnant M, Jakesz R, and Oberhuber G
- Subjects
- Austria epidemiology, Biopsy, Biopsy, Needle, Breast Neoplasms metabolism, Female, Humans, Immunoenzyme Techniques, Middle Aged, Multicenter Studies as Topic, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Neoplasm Staging, Prognosis, Prospective Studies, Receptor, ErbB-2 metabolism, Breast Neoplasms classification, Breast Neoplasms diagnosis
- Abstract
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.
- Published
- 2001
97. Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer.
- Author
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Birner P, Oberhuber G, Stani J, Reithofer C, Samonigg H, Hausmaninger H, Kubista E, Kwasny W, Kandioler-Eckersberger D, Gnant M, and Jakesz R
- Subjects
- Adult, Aged, Antibodies, Monoclonal metabolism, Breast Neoplasms mortality, Carcinoma metabolism, Disease-Free Survival, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Middle Aged, Receptors, Estrogen metabolism, Time Factors, United States, United States Food and Drug Administration, Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Medical Oncology methods, Medical Oncology standards, Prognosis, Receptor, ErbB-2 biosynthesis
- Abstract
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.
- Published
- 2001
98. Treatment of advanced breast cancer with vinorelbine and docetaxel with or without human granulocyte colony-stimulating factor.
- Author
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Kornek GV, Ulrich-Pur H, Penz M, Haider K, Kwasny W, Depisch D, Kovats E, Lang F, Schneeweiss B, and Scheithauer W
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Docetaxel, Drug Administration Schedule, Female, Follow-Up Studies, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Leukocyte Count, Middle Aged, Neutrophils cytology, Neutrophils drug effects, Paclitaxel administration & dosage, Paclitaxel adverse effects, Vinblastine administration & dosage, Vinblastine adverse effects, Vinorelbine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Paclitaxel analogs & derivatives, Taxoids, Vinblastine analogs & derivatives
- Abstract
Purpose: A multicenter phase II trial was performed to investigate the efficacy and tolerance of docetaxel, vinorelbine with or without recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with metastatic breast cancer., Patients and Methods: Between February 1998 and March 1999, 57 patients participated in this trial. Forty-two patients received this combination as first-line and 15 patients as second-line chemotherapy, including 10 patients who had failed anthracyclines. Therapy consisted of vinorelbine 30 mg/m(2) on days 1 and 15 and docetaxel 30 mg/m(2) on days 1, 8, and 15 every 4 weeks. Depending on the absolute neutrophil counts on the day of scheduled chemotherapeutic drug administration, a 5-day course of G-CSF 5 microg/kg/d was given., Results: The overall response rate was 64.3% (95% confidence interval, 48.1% to 78.4%) in patients receiving docetaxel plus vinorelbine as first-line chemotherapy, including eight complete (19%) and 19 partial remissions (45.3%); 11 patients (26.2%) had disease stabilization, and only four (9.5%) progressed. Second-line treatment with this regimen resulted in eight (53.3%) of 15 objective responses, four had stable disease, and three had progressive disease. The median time to progression was 12 months in the first-line and 9.8 months in the second-line setting, respectively. After a median follow-up time of 18 months, 38 patients (65%) were still alive with metastatic disease. Myelosuppression was commonly observed; World Health Organization grade 3 or 4 neutropenia both occurred in 18 patients (32%) and was complicated by septicemia in four cases; grade 3 or 4 thrombocytopenia was seen in two patients (4%), and grade 3 anemia was seen in only one patient (2%). Severe (grade 3) nonhematologic toxicity, except for alopecia, was rarely observed and included nausea/vomiting in two patients (4%), and stomatitis, peripheral neuropathy, and skin toxicity each in one patient., Conclusion: Our data suggest that docetaxel and vinorelbine with or without G-CSF is an effective and fairly well tolerated regimen for the treatment of advanced breast cancer. It might be particularly useful in patients previously exposed to adjuvant or palliative anthracyclines and/or alkylating agents.
- Published
- 2001
- Full Text
- View/download PDF
99. Treatment of advanced, refractory breast cancer with alternating docetaxel and epirubicin/cyclophosphamide plus human granulocyte colony-stimulating factor.
- Author
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Kwasny W, Kornek G, Haider K, Valencak J, Ulrich-Pur H, Penz M, Lang F, Depisch D, and Scheithauer W
- Subjects
- Adult, Aged, Breast Neoplasms mortality, Cyclophosphamide adverse effects, Docetaxel, Epirubicin adverse effects, Female, Granulocyte Colony-Stimulating Factor adverse effects, Humans, Middle Aged, Paclitaxel administration & dosage, Paclitaxel adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Cyclophosphamide administration & dosage, Epirubicin administration & dosage, Granulocyte Colony-Stimulating Factor administration & dosage, Paclitaxel analogs & derivatives, Taxoids
- Abstract
Purpose: A phase II study was performed to investigate the efficacy and tolerance of alternating docetaxel and epirubicin/cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with advanced breast cancer who failed previous non-anthracycline/taxane-containing palliative chemotherapy., Patients and Methods: Between November 96 and June 98, a total of 45 patients participated in this trial. Chemotherapy consisted of docetaxel 100 mg/m2 given as a 1-h infusion on day 1, and epirubicin 100 mg/m2 plus cyclophosphamide 800 mg/m2 both administered on day 21. G-CSF 5 microg/kg/day was given subcutaneously from days 22-28 during each cycle. Treatment courses were repeated every 42 days for a total of three courses unless prior evidence of progressive disease., Results: The overall response rate was 57.8% (95% confidence interval, 42.1-72.3%), including seven complete (15.5%) and 19 partial remissions (42.3%); nine patients (20%) had stabilization of disease and 10 (22.3%) progressed. The median time to treatment failure was 7.0 months (range 1.5-26.0), and the median overall survival time 15.0 months (range 2.0-37.0+) with 12 patients (27%) currently still alive with metastatic disease. Myelosuppression was commonly observed with WHO grade 3/4 neutropenia in 20 patients (44%) complicated by septicemia in five (11%). Severe nonhematologic toxicity included stomatitis in five patients (11%), skin and peripheral neurotoxicity each in one patient; alopecia was seen in all 45 patients with complete hair loss in 26 (58%)., Conclusions: Our data suggest that alternating docetaxel and epirubicin/cyclo-phosphamide plus G-CSF is an effective and tolerable second-line combination regimen for the treatment of advanced breast cancer.
- Published
- 2000
- Full Text
- View/download PDF
100. Treatment of advanced breast cancer with gemcitabine and vinorelbine plus human granulocyte colony-stimulating factor.
- Author
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Haider K, Kornek GV, Kwasny W, Weinländer G, Valencak J, Lang F, Püribauer F, Kovats E, Depisch D, and Scheithauer W
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Deoxycytidine analogs & derivatives, Drug Administration Schedule, Female, Follow-Up Studies, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte Colony-Stimulating Factor adverse effects, Humans, Middle Aged, Survival Analysis, Vinblastine administration & dosage, Vinblastine adverse effects, Vinblastine analogs & derivatives, Vinorelbine, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Purpose: A phase II trial was performed to investigate the efficacy and tolerance of gemcitabine, vinorelbine, and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer., Patients and Methods: Between April 96 and August 97, 60 patients entered this trial. Forty-five patients were previously untreated and 15 patients had failed previous palliative chemotherapy with (n = 10) or without anthracyclines (n = 5). Therapy consisted of gemcitabine 1000 mg/m2 on days 1 + 15 + 21 and vinorelbine 40 mg/m2 on days 1 + 21, both diluted in 250 ml saline and infused over 30 min. G-CSF was administered at 5 microg/kg/day subcutaneously from days 2-6 and 22-26. Courses were repeated every 5 weeks. Treatment was continued in case of response or stable disease until a total of six courses., Results: The overall response rate was 55.5% for patients who had not received prior palliative chemotherapy (95% confidence interval, 40%-70.3%), including 5 CR (11.1%) and 20 PR (44.4%); 12 patients (27%) had stable disease (SD), and 8 (18%) progressed. Second-line treatment with this regimen resulted in 6/15 (40%) objective remissions, 5 had SD, and 4 PD. The median time to progression was 9.5 months (range, 1.5-28) in previously untreated patients, and 7.0 months (range, 2-23) in those who had failed prior chemotherapy. After a median follow-up time of 15 months, 44 patients (73%) are still alive with metastatic disease. Myelosuppression was commonly observed, though WHO 3 and 4 neutropenia occured in only 9 (15%) and 2 patients (3%), and was never complicated by septicaemia; grade 3 anemia was noted in 2 patients. Severe (WHO grade 3) nonhematologic toxicity was rarely observed, and included nausea/emesis in 3 and constipation in 2 patients., Conclusions: Our data suggest that gemcitabine and vinorelbine plus G-CSF is an effective and tolerable first- as well as second-line combination regimen for treatment of advanced breast cancer.
- Published
- 1999
- Full Text
- View/download PDF
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