title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Patients (tumor size > or = 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/m(2), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gynecology and Obstetrics, Goethe University, Frankfurt am Main, Germany. minckwitz@em.uni-frankfurt.de
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: S D
authors.initials: SD
authors.lastname: Costa
authors.forename: G
authors.initials: G
authors.lastname: Raab
authors.forename: J U
authors.initials: JU
authors.lastname: Blohmer
authors.forename: H
authors.initials: H
authors.lastname: Eidtmann
authors.forename: J
authors.initials: J
authors.lastname: Hilfrich
authors.forename: E
authors.initials: E
authors.lastname: Merkle
authors.forename: C
authors.initials: C
authors.lastname: Jackisch
authors.forename: G
authors.initials: G
authors.lastname: Gademann
authors.forename: A H
authors.initials: AH
authors.lastname: Tulusan
authors.forename: W
authors.initials: W
authors.lastname: Eiermann
authors.forename: E
authors.initials: E
authors.lastname: Graf
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010349:Patient Compliance; D011300:Preoperative Care; D011446:Prospective Studies; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids
chemical_list: D043823:Taxoids; D013629:Tamoxifen; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel