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Dose-Dense Doxorubicin, Docetaxel, and Granulocyte Colony-Stimulating Factor Support With or Without Tamoxifen as Preoperative Therapy in Patients With Operable Carcinoma of the Breast: A Randomized, Controlled, Open Phase IIb Study

From the Department of Gynecology and Obstetrics, Goethe University, Frankfurt am Main; Red Cross Gynecological Hospital, Munich; Department of Gynecology, Charité Hospital, Humboldt University, Berlin; Department of Gynecology, University of Kiel, Kiel; Henrietten-Stift Gynecological Hospital, Hannover; am Berg Gynecological Hospital, Stuttgart; Department of Gynecology, University of Münster, Münster; Department of Radiotherapy, University of Magdeburg, Magdeburg; Bayreuth Gynecological Hospital, Bayreuth; and Department of Medical Biometry and Statistics, University Hospital Freiburg, Germany.

Address reprint requests to Gunter von Minckwitz, MD, PhD, Zentrum der Frauenheilkunde und Geburtshilfe, J.W. Goethe-Universität Frankfurt am Main, Theodor-Stern Kai 7, D-60590 Frankfurt am Main, Germany; email: minckwitz{at}em.uni-frankfurt.de

PURPOSE: To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer.

PATIENTS AND METHODS: Patients (tumor size 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m² and docetaxel 75 mg/m², either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment.

RESULTS: Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of -1.2% in favor of ADoc, with a 95% confidence interval of -8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status.

CONCLUSION: A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.

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