Publications 2008

Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy

Michael Gnant, Brigitte Mlineritsch, Gero Luschin-Ebengreuth, Franz Kainberger, Helmut Kässmann, Jutta Claudia Piswanger-Sölkner,Michael Seifert, Ferdinand Ploner, Christian Menzel, Peter Dubsky, Florian Fitzal, Vesna Bjelic-Radisic, Günther Steger, Richard Greil, Christian Marth, Ernst Kubista, Hellmut Samonigg, Peter Wohlmuth, Martina Mittlböck, Raimund Jakesz, on behalf of the Austrian Breast and Colorectal Cancer Study Group

Lancet Oncol 2008; 9: 840–49

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Cyclin D1 Expression in Breast Cancer Patients Receiving Adjuvant Tamoxifen-Based Therapy

Margaretha Rudas, Martina Lehnert, Anh Huynh, Raimund Jakesz, Christian Singer,Sigurd Lax, Walter Schippinger, Otto Dietze, Richard Greil, Wolfgang Stiglbauer, Werner Kwasny, Renate Grill, Michael Stierer, Michael F. X. Gnant and Martin Filipits for the Austrian Breast and Colorectal Cancer Study Group

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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.

Clin Cancer Res 2008;14(6) March 15, 2008

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Anemia Is a Significant Prognostic Factor in Local Relapse-Free Survival of Premenopausal Primary Breast Cancer Patients Receiving Adjuvant Cyclophosphamide/Methotrexate/5-Fluorouracil Chemotherapy

Peter Dubsky, Paul Sevelda, Raimund Jakesz, Hubert Hausmaninger, Hellmut Samonigg, Michael Seifert, Ursula Denison, Brigitte Mlineritsch, Günther Steger, Werner Kwasny, Herbert Stöger, Rupert Bartsch, Michael Stierer, Susanne Taucher, Michael Fridrik, Walter Schippinger, Richard Greil, Richard Pötter, Michael Gnant

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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

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.

Clin Cancer Res 2008;14(7) April 1, 2008

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