title: Hormone receptor status influences the locoregional benefit of trastuzumab in patients with nonmetastatic breast cancer.
abstract: BACKGROUND
  Previous studies have shown that hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status influence the outcome of locoregional treatments. However, the interrelationship of these factors with trastuzumab is unclear. In this study, the role of HR and HER2 status on the locoregional benefit of trastuzumab treatment was investigated in patients with nonmetastatic breast cancer.
  
  
  METHODS
  Locoregional outcomes of 5683 women treated at The University of Texas MD Anderson Cancer Center from 2000 to 2008 for invasive breast cancer were analyzed using Kaplan-Meier and Cox regression methods to compare 6 subgroups: HR-positive (HR+)/HER2-negative (HER2-), HR-/HER2- (triple-negative), HR+/HER2+ with or without trastuzumab, and HR-/HER2+ with or without trastuzumab.
  
  
  RESULTS
  Overall, locoregional recurrence (LRR) was 5% at 5 years among patients with HER2+ disease. Patients with HR+/HER2+ disease treated with trastuzumab had half the rate of LRR as patients who did not receive trastuzumab, whereas patients with HR-/HER2+ disease had similar rates of LRR regardless of trastuzumab treatment. On Cox regression analysis comparing LRR risk to the cohort with HR+/HER2- disease, only the HR+/HER2+ cohort treated with trastuzumab had similar LRR risk (hazard ratio = 1.24, 95% confidence interval = 0.56-2.73, P = .591). All other subgroups, including the HR+/HER2+ cohort who did not receive trastuzumab, had significantly worse outcomes. LRR risk was highest among patients with triple-negative disease (hazard ratio = 4.73, 95% confidence interval = 3.42-6.54, P < .001).
  
  
  CONCLUSIONS
  Among patients with HR+/HER2+ disease, treatment with trastuzumab reduces LRR risk to the more favorable outcome of patients with HR+/HER2- disease. In contrast, the increased LRR risk among patients with HR-/HER2+ disease remains despite treatment with trastuzumab. Additional locoregional strategies are needed in this subgroup of patients.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kim
authors.forename: Shaheenah
authors.initials: S
authors.lastname: Dawood
authors.forename: Pamela
authors.initials: P
authors.lastname: Allen
authors.forename: Aysegul A
authors.initials: AA
authors.lastname: Sahin
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Smith
authors.forename: Eric A
authors.initials: EA
authors.lastname: Strom
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab