• 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, and Austrian Breast and Colorectal Cancer Study Group.
• Department of Surgery, Medical University Vienna, Vienna, Austria. peter.dubsky@meduniwien.ac.at
• Clin Cancer Res. 2008 Apr 1; 14 (7): 2082-7.

PurposeTo 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 DesignFour 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.ResultsOf 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.ConclusionPremenopausal 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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