title: Differential impact of hormone receptor status on survival and recurrence for HER2 receptor-positive breast cancers treated with Trastuzumab.
abstract: BACKGROUND
  Hormone receptor status has major implications for treatment and survival of breast cancer. Yet the impact of hormone receptor status on outcome after Trastuzumab has received little attention. The objective here was to explore any differential effects of Trastuzumab treatment (Trast +ve) on Luminal B HER2 or HER2+(ER-) breast cancer subtypes.
  
  
  METHODS
  A cohort of 469 HER2 receptor-positive breast cancers was categorised by molecular subtype and Trastuzumab treatment. Effects of Trastuzumab treatment on survival, locoregional recurrence and distant metastasis were investigated by subtype, using univariate and multivariate analysis.
  
  
  RESULTS
  Trast +ve Luminal B HER2 patients had significant improvements in 5-year DFS (p < 0.001) and OS (p < 0.001), while Trast +ve HER2+(ER-) patients had significant improvements in 5-year DFS (p = 0.012) alone. Only Trast +ve Luminal B HER2 cancers displayed a significant reduction in LRR rates (p < 0.001). A significant reduction in distant metastasis rates was seen in Trast +ve Luminal B HER2 (p < 0.001) and HER2+(ER-) (p = 0.009) cancers. Interestingly, bone metastasis rates in Trast +ve Luminal B HER2 cancers demonstrated the greatest reduction (36.2-6.7%). Multivariate analysis of Trast +ve patients found no difference in distant metastasis rates (p = 0.96) between subtypes. Significantly, lower LRR rates were seen in Trast +ve Luminal B HER2 cancers, compared to Trast +ve HER2+(ER-) (p = 0.018).
  
  
  CONCLUSIONS
  An enhanced response to Trastuzumab was seen in Luminal B HER2 cancers. We highlight how Trastuzumab treatment changed the natural history of the HER2 receptor-positive breast cancer, demonstrating improved efficacy in changing the outcome of hormone receptor-positive patients.
authors.affiliation: Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland.
authors.forename: Andrew
authors.initials: A
authors.lastname: McGuire
authors.affiliation: School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland.
authors.forename: Olga
authors.initials: O
authors.lastname: Kalinina
authors.affiliation: School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland.
authors.forename: Emma
authors.initials: E
authors.lastname: Holian
authors.affiliation: Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Curran
authors.affiliation: Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland.
authors.forename: Carmel A
authors.initials: CA
authors.lastname: Malone
authors.affiliation: Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland.
authors.forename: Ray
authors.initials: R
authors.lastname: McLaughlin
authors.affiliation: Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland.
authors.forename: Aoife
authors.initials: A
authors.lastname: Lowery
authors.affiliation: Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland. james.brown@nuigalway.ie.
authors.forename: James A L
authors.identifier: http://orcid.org/0000-0002-3155-0334
authors.initials: JAL
authors.lastname: Brown
authors.affiliation: Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland. michael.kerin@nuigalway.ie.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kerin
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D000068878:Trastuzumab / Q000008:administration & dosage*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; Distant; HER2; HER2+(ER−); Luminal B; Luminal B HER2; Metastasis; Survival; Trastuzumab