title: Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study.
abstract: BACKGROUND
  In gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status.
  
  
  METHODS
  We evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups.
  
  
  RESULTS
  Median follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002).
  
  
  CONCLUSIONS
  Presenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials.
authors.forename: Ines
authors.initials: I
authors.lastname: Vaz-Luis
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Ottesen
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Hughes
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Richard L
authors.initials: RL
authors.lastname: Theriault
authors.forename: John
authors.initials: J
authors.lastname: Wilson
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Niland
authors.forename: Jane C
authors.initials: JC
authors.lastname: Weeks
authors.forename: Nancy U
authors.initials: NU
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone