title: HER2 and response to paclitaxel in node-positive breast cancer.
abstract: BACKGROUND
  The status of human epidermal growth factor receptor type 2 (HER2) in breast-cancer cells predicts clinical outcomes in women who receive adjuvant anthracycline-based chemotherapy. We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both.
  
  
  METHODS
  We randomly selected 1500 women from 3121 women with node-positive breast cancer who had been randomly assigned to receive doxorubicin (60, 75, or 90 mg per square meter of body-surface area) plus cyclophosphamide (600 mg per square meter) for four cycles, followed by four cycles of paclitaxel (175 mg per square meter) or observation. Tissue blocks from 1322 of these 1500 women were available. Immunohistochemical analyses of these tissue specimens for HER2 with the CB11 monoclonal antibody against HER2 or with a polyclonal-antibody assay kit and fluorescence in situ hybridization for HER2 amplification were performed.
  
  
  RESULTS
  No interaction was observed between HER2 positivity and doxorubicin doses above 60 mg per square meter. HER2 positivity was, however, associated with a significant benefit from paclitaxel. The interaction between HER2 positivity and the addition of paclitaxel to the treatment was associated with a hazard ratio for recurrence of 0.59 (P=0.01). Patients with a HER2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status, but paclitaxel did not benefit patients with HER2-negative, estrogen-receptor-positive cancers.
  
  
  CONCLUSIONS
  The expression or amplification, or both, of HER2 by a breast cancer is associated with a benefit from the addition of paclitaxel after adjuvant treatment with doxorubicin (<60 mg per square meter) plus cyclophosphamide in node-positive breast cancer, regardless of estrogen-receptor status. Patients with HER2-negative, estrogen-receptor-positive, node-positive breast cancer may gain little benefit from the administration of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide.
authors.affiliation: Breast Oncology Program,University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA. hayesdf@umich.edu
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: Ann D
authors.initials: AD
authors.lastname: Thor
authors.forename: Lynn G
authors.initials: LG
authors.lastname: Dressler
authors.forename: Donald
authors.initials: D
authors.lastname: Weaver
authors.forename: Susan
authors.initials: S
authors.lastname: Edgerton
authors.forename: David
authors.initials: D
authors.lastname: Cowan
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Goldstein
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: I Craig
authors.initials: IC
authors.lastname: Henderson
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen