title: Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers.
abstract: OBJECTIVE
  In the adjuvant setting, taxanes modestly improve clinical outcome and survival. The goal of the present study was to define the efficacy of neoadjuvant docetaxel in treatment-naïve large, locally advanced breast cancers and to better understand docetaxel's mechanism of action by evaluating biomarker modulation in response to treatment.
  
  
  METHODS
  Fifty-one patients were enrolled. Patients received four cycles of docetaxel (100 mg/m2 q3weeks) followed by surgery and four cycles of doxorubicin and cyclophosphamide (60/600 mg/m2 q3weeks). Radiation and hormonal therapy were given if clinically indicated. Clinical responses were assessed at completion of neoadjuvant docetaxel. Pathological responses were considered complete (pCR) if no tumor cells were identified in the surgical specimen or near complete (npCR) if only occasional scattered tumor cells were seen. Proliferation (Ki-67) and apoptosis (cleaved caspase-3) were measured by IHC in tissue obtained at baseline and at surgery.
  
  
  RESULTS
  The median tumor size was 9 cm (range 4-30 cm). Objective response rate was 75% with clinical complete response in 27%, partial response in 48%, and stable disease in 25% of the patients. pCR/npCR was reported in 20% of patients. With a median follow up of 28 months, 98 and 78% of the patients were alive at 12 and 24 months, respectively. Overall survival at 24 months was significantly better in patients who achieved a clinical response, 85 versus 51%, p = 0.008, but pCR/npCR was not a significant predictor of outcome. Apoptosis was induced in clinical responders (p = 0.002), while the proliferation index did not change significantly. In patients who had no clinical response to docetaxel, neither apoptosis nor proliferation changed significantly.
  
  
  CONCLUSIONS
  Neoadjuvant single agent docetaxel is effective in treating patients with large locally advanced breast cancer and clinical response is associated with improved survival. Docetaxel acts therapeutically by inducing apoptosis and this can be used as a marker of response.
authors.affiliation: Breast Center and the Department of Medicine, Baylor College of Medicine and the Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Yee-Lu
authors.initials: YL
authors.lastname: Tham
authors.forename: L Fernando
authors.initials: LF
authors.lastname: Gomez
authors.forename: Syed
authors.initials: S
authors.lastname: Mohsin
authors.forename: M Carolina
authors.initials: MC
authors.lastname: Gutierrez
authors.forename: Heidi
authors.initials: H
authors.lastname: Weiss
authors.forename: Susan G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: Richard M
authors.initials: RM
authors.lastname: Elledge
authors.forename: Gary C
authors.initials: GC
authors.lastname: Chamness
authors.forename: C Kent
authors.initials: CK
authors.lastname: Osborne
authors.forename: D Craig
authors.initials: DC
authors.lastname: Allred
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D016019:Survival Analysis; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel