title: HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma.
abstract: BACKGROUND
  The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly.
  
  
  METHODS
  The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a >/= 50% regression in clinical tumor size prior to surgery.
  
  
  RESULTS
  In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu-negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2-13.0) in favor of docetaxel. Women who had HER-2/neu-negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu-positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates.
  
  
  CONCLUSIONS
  HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu-negative tumors to match that observed in women who have HER-2/neu-positive tumors treated with AC alone.
authors.affiliation: Department of Surgery, University of Texas Health Science Center-San Antonio, San Antonio, Texas 78284, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Learn
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.forename: Michelle
authors.initials: M
authors.lastname: McNutt
authors.forename: Gary B
authors.initials: GB
authors.lastname: Chisholm
authors.forename: Brad H
authors.initials: BH
authors.lastname: Pollock
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Rousseau
authors.forename: Frances E
authors.initials: FE
authors.lastname: Sharkey
authors.forename: Anatolio B
authors.initials: AB
authors.lastname: Cruz
authors.forename: Morton S
authors.initials: MS
authors.lastname: Kahlenberg
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D003520:Cyclophosphamide; D000077143:Docetaxel; D004317:Doxorubicin; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D016159:Tumor Suppressor Protein p53