title: Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study analysis.
abstract: BACKGROUND
  Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated.
  
  
  METHODS
  Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse.
  
  
  RESULTS
  Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p=0.003).
  
  
  CONCLUSIONS
  Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression.
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Willemien
authors.initials: W
authors.lastname: van de Water
authors.forename: Duveken B Y
authors.initials: DB
authors.lastname: Fontein
authors.forename: Johanna G H
authors.initials: JG
authors.lastname: van Nes
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: Elysée T M
authors.initials: ET
authors.lastname: Hille
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Tammy
authors.initials: T
authors.lastname: Robson
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Liefers
authors.forename: Rudi M H
authors.initials: RM
authors.lastname: Roumen
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Elma Meershoek-Klein
authors.initials: EM
authors.lastname: Kranenbarg
authors.forename: Johan W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
mesh_terms: D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen; C056516:exemestane