title: Discordance in hormone receptor status among primary, metastatic, and second primary breast cancers: biological difference or misclassification?
abstract: BACKGROUND
  Discordance in hormone receptor status has been observed between two breast tumors of the same patients; however, the degree of heterogeneity is debatable with regard to whether it reflects true biological difference or the limited accuracy of receptor assays.
  
  
  METHODS
  A Bayesian misclassification correction method was applied to data on hormone receptor status of two primary breast cancers from the Surveillance, Epidemiology, and End Results database between 1990 and 2010 and to data on primary breast cancer and paired recurrent/metastatic disease assembled from a meta-analysis of the literature published between 1979 and 2014.
  
  
  RESULTS
  The sensitivity and specificity of the estrogen receptor (ER) assay were estimated to be 0.971 and 0.920, respectively. After correcting for misclassification, the discordance in ER between two primary breast cancers was estimated to be 1.2% for synchronous ipsilateral pairs, 5.0% for synchronous contralateral pairs, 14.6% for metachronous ipsilateral pairs, and 25.0% for metachronous contralateral pairs. Technical misclassification accounted for 53%-83% of the ER discordance between synchronous primary cancers and 11%-25% of the ER discordance between metachronous cancers. The corrected discordance in ER between primary tumors and recurrent or metastatic lesions was 12.4%, and there were more positive-to-negative changes (10.1%) than negative-to-positive changes (2.3%). Similar patterns were observed for progesterone receptor (PR), although the overall discordance in PR was higher.
  
  
  CONCLUSIONS
  A considerable proportion of discordance in hormone receptor status can be attributed to misclassification in receptor assessment, although the accuracy of receptor assays was excellent. Biopsy of recurrent tumors for receptor retesting should be conducted after considering feasibility, cost, and previous ER/PR status.
authors.affiliation: Center for Clinical Cancer Genetics and Global Health, Department of Medicine and Department of Health Studies, University of Chicago, Chicago, Illinois, USA; Department of Mathematics and Statistics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sighoko
authors.affiliation: Center for Clinical Cancer Genetics and Global Health, Department of Medicine and Department of Health Studies, University of Chicago, Chicago, Illinois, USA; Department of Mathematics and Statistics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Juxin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Clinical Cancer Genetics and Global Health, Department of Medicine and Department of Health Studies, University of Chicago, Chicago, Illinois, USA; Department of Mathematics and Statistics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ningqi
authors.initials: N
authors.lastname: Hou
authors.affiliation: Center for Clinical Cancer Genetics and Global Health, Department of Medicine and Department of Health Studies, University of Chicago, Chicago, Illinois, USA; Department of Mathematics and Statistics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Gustafson
authors.affiliation: Center for Clinical Cancer Genetics and Global Health, Department of Medicine and Department of Health Studies, University of Chicago, Chicago, Illinois, USA; Department of Mathematics and Statistics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada dhuo@health.bsd.uchicago.edu.
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
mesh_terms: D001499:Bayes Theorem; D001706:Biopsy; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011980:Receptors, Progesterone
keywords: Breast neoplasms; Discordance; Estrogen receptor; Metastasis biopsy; Metastatic breast carcinoma; Second primary neoplasm