title: A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases.
abstract: BACKGROUND
  The discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed.
  
  
  METHODS
  A literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions.
  
  
  RESULTS
  We selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I(2)=91%, p<0.0001), PgR (I(2)=79%, p<0.0001) and HER2 (I(2)=77%, p<0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16-35%) for ER, 33% (95% CI: 29-38%) for PgR and 8% (95% CI: 6-10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p=0.0183), respectively. The same figures were 46% and 15% for PgR (p<0.0001), and 13% and 5% for HER2 (p=0.0004).
  
  
  CONCLUSIONS
  Our findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.
authors.affiliation: European Institute of Oncology, Medical Oncology, via Ripamonti 435, Milan, Italy. Electronic address: gaetano.aurilio@ieo.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Aurilio
authors.affiliation: European Institute of Oncology, Division of Epidemiology and Biostatistics, via Ripamonti 435, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Disalvatore
authors.affiliation: European Institute of Oncology, Division of Pathology, via Ripamonti 435, Milan, Italy; University of Milan, School of Medicine, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.affiliation: European Institute of Oncology, Division of Epidemiology and Biostatistics, via Ripamonti 435, Milan, Italy; Department of Statistics and Quantitative Methods, University of Milan-Bicocca, via Bicocca degli Arcimboldi 8, 20126 Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.affiliation: European Institute of Oncology, Division of Pathology, via Ripamonti 435, Milan, Italy; University of Milan, School of Medicine, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: European Institute of Oncology, Medical Oncology, via Ripamonti 435, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: European Institute of Oncology, Medical Oncology, via Ripamonti 435, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Adamoli
authors.affiliation: European Institute of Oncology, Medical Oncology, via Ripamonti 435, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Munzone
authors.affiliation: European Institute of Oncology, Medical Oncology, via Ripamonti 435, Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Sciandivasci
authors.affiliation: Second University of Naples, Medical Oncology, via Pansini 5, Naples, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: De Vita
authors.affiliation: European Institute of Oncology, Medical Oncology, via Ripamonti 435, Milan, Italy.
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: European Institute of Oncology, Medical Oncology, via Ripamonti 435, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Nolè
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Concordance; HER2; Hormone receptors