title: Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment.
abstract: OBJECTIVE
  Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision.
  
  
  METHODS
  A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland-Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2.
  
  
  RESULTS
  From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538-0.686), PgR (k0.659; 95% CI, 0580-0.737), Ki-67 (k0.609; 95% CI, 0.534-0.684) and grading (k0.669; 95% CI, 0.569-0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444-0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified.
  
  
  CONCLUSIONS
  In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results.
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy. Electronic address: laura.orlando68@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Orlando
authors.affiliation: Pathology Division, European Institute of Oncology, University of Milan, 20141 Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Medical Oncology & Breast Unit, University of Verona, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Eufemia Stefania
authors.initials: ES
authors.lastname: Lutrino
authors.affiliation: Biostatistics, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Medical Oncology & Breast Unit, University of Verona, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Carbognin
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Schiavone
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Quaranta
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Palma
authors.initials: P
authors.lastname: Fedele
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Caliolo
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Calvani
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Criscuolo
authors.affiliation: Medical Oncology Division & Breast Unit, 72100 Brindisi, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinieri
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / 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; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D015588:Observer Variation; D010338:Pathology, Clinical; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Early breast cancer; Pathology report