title: Multifocal breast cancer documented in large-format histology sections: long-term follow-up results by molecular phenotypes.
abstract: BACKGROUND
  The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail.
  
  
  METHODS
  In total, 444 consecutive invasive breast cancers that were documented in large-format histology slides and worked up with detailed radiologic-pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes.
  
  
  RESULTS
  Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14-fold respectively 2.75-fold risk of cancer-related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)-positive cancers; estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) cancers; or basal-like cancers had a 2.18-fold, 2.33-fold, and 4.07-fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2-positive, and basal-like cancers were associated with significantly better long-term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple-negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant.
  
  
  CONCLUSIONS
  Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal-like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters.
authors.affiliation: Department of Pathology and Clinical Cytology, Falun Central Hospital, Falun, Sweden. gyula.pekar@ltdalarna.se
authors.forename: Gyula
authors.initials: G
authors.lastname: Pekar
authors.forename: Syster
authors.initials: S
authors.lastname: Hofmeyer
authors.forename: László
authors.initials: L
authors.lastname: Tabár
authors.forename: Miklós
authors.initials: M
authors.lastname: Tarján
authors.forename: Tony Hsiu-Hsi
authors.initials: TH
authors.lastname: Chen
authors.forename: Amy Ming-Fang
authors.initials: AM
authors.lastname: Yen
authors.forename: Sherry Yueh-Hsia
authors.initials: SY
authors.lastname: Chiu
authors.forename: Dan
authors.initials: D
authors.lastname: Hellberg
authors.forename: Mária
authors.initials: M
authors.lastname: Gere
authors.forename: Tibor
authors.initials: T
authors.lastname: Tot
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D010641:Phenotype; D011379:Prognosis; 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