title: Discordances in estrogen receptor status, progesterone receptor status, and HER2 status between primary breast cancer and metastasis.
abstract: BACKGROUND
  The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance.
  
  
  METHODS
  Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3+ in immunohistochemistry or if amplification ratio was >2 in fluorescent in situ hybridization.
  
  
  RESULTS
  From a cohort of 489 patients with mBC, 269 patients had histopathological samples of metastatic relapse. Histopathological analysis of the specimen confirmed the diagnosis of mBC in 235 patients. Discordance in one or more receptors between primary breast cancer and mBC was found in 99 patients (42%). A switch in receptor status was identified for ER in 17% of tumors (p = 4 × 10(-3)), PR in 29% of cancers (p < 4 × 10(-4)), and HER2 in 4% of lesions (p = .16). Exposure to chemotherapy and to anthracycline-based chemotherapy was statistically associated with switches in ER status. Seven (2%) second malignancies and three benign diseases (1%) were diagnosed.
  
  
  CONCLUSIONS
  This study confirms that discordance in ER and PR receptor expression between the primary breast tumor and the corresponding metastatic lesions is high, whereas HER2 status remains relatively constant. Chemotherapy, and specifically anthracycline-based chemotherapy, was associated with switch in ER status. These results were obtained in a selected population of patients; further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting.
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France. elsa.curtit7@wanadoo.fr
authors.forename: Elsa
authors.initials: E
authors.lastname: Curtit
authors.forename: Virginie
authors.initials: V
authors.lastname: Nerich
authors.forename: Laura
authors.initials: L
authors.lastname: Mansi
authors.forename: Loic
authors.initials: L
authors.lastname: Chaigneau
authors.forename: Laurent
authors.initials: L
authors.lastname: Cals
authors.forename: Cristian
authors.initials: C
authors.lastname: Villanueva
authors.forename: Fernando
authors.initials: F
authors.lastname: Bazan
authors.forename: Philippe
authors.initials: P
authors.lastname: Montcuquet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meneveau
authors.forename: Sophie
authors.initials: S
authors.lastname: Perrin
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Algros
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Estrogen receptor; Human epidermal growth factor receptor 2; Progesterone receptor