title: Human epidermal growth factor receptor 2 status correlates with lymph node involvement in patients with estrogen receptor (ER) negative, but with grade in those with ER-positive early-stage breast cancer suitable for cytotoxic chemotherapy.
abstract: OBJECTIVE
  Human epidermal growth factor receptor 2 (HER-2) expression is associated with increased risk of high-grade disease, nodal metastasis, and absence of estrogen receptors (ERs) in early breast cancer. We tested interactions between ER and HER-2 to determine if they may modulate breast cancer nodal metastasis and proliferation.
  
  
  METHODS
  Tumors from the Cancer Research UK Taxotere as Adjuvant Chemotherapy phase III trial were tested for HER-2 using current diagnostic procedures. ER status, progesterone status, clinicopathologic characteristics, and patient age were included in a logistic regression analysis to identify associations with HER-2 status (positive v negative).
  
  
  RESULTS
  A total of 841 (23.6%) of 3,565 samples were HER-2 positive (3+ by immunohistochemistry or positive by fluorescent in situ hybridization). ER-negative tumors were more likely to be HER-2 positive than were ER-positive tumors (odds ratio [OR] = 1.87, ER negative v ER positive; P < .001). For ER-positive tumors, risk of HER-2 positivity increased by grade (OR = 7.6, grade 3 v grade 1; P < .001) but not nodal status (OR = 1.3, four or more positive nodes v node negative; P = .08). Conversely, ER negative node-positive tumors were markedly more frequently HER-2 positive than node-negative cases (OR = 3.05, four or more positive nodes v node negative; P < .001) but independent of grade (OR = 0.82, grade 3 v grade 1; P = .76).
  
  
  CONCLUSIONS
  In early breast cancer patients selected for cytotoxic chemotherapy, we identified significant interactions between HER-2 and ER expression that correlate with tumor pathology. In ER-positive breast cancers, HER-2 expression correlates with grade, not nodal metastasis. In ER-negative breast cancers, HER-2 expression correlates with increased nodal positivity, not grade. ER and HER-2 expression may modify tumor pathology via ER/HER-2-mediated cross talk.
authors: Endocrine Cancer Research Group, Edinburgh University Cancer Research Centre, Western General Hospital, Edinburgh, United Kingdom. John.Bartlett@ed.ac.uk
authors: John M S
authors: JM
authors: Bartlett
authors: Ian O
authors: IO
authors: Ellis
authors: Mitch
authors: M
authors: Dowsett
authors: Elizabeth A
authors: EA
authors: Mallon
authors: David A
authors: DA
authors: Cameron
authors: Stephen
authors: S
authors: Johnston
authors: Emma
authors: E
authors: Hall
authors: Roger
authors: R
authors: A'Hern
authors: Clare
authors: C
authors: Peckitt
authors: Judith M
authors: JM
authors: Bliss
authors: Lindsay
authors: L
authors: Johnson
authors: Peter
authors: P
authors: Barrett-Lee
authors: Paul
authors: P
authors: Ellis
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone