title: A novel morphologic-molecular recurrence predictive model refines traditional prognostic tools for invasive breast carcinoma.
abstract: BACKGROUND
  Histologic grade, TNM stage, and Nottingham Prognostic Index are traditional prognostic tools for breast cancer. "IHC-molecular" classification of breast cancer can also identify patients at different recurrence risks and provides insight into cancer therapy. However, cancers in each group are heterogeneous. A model based on the comprehensive analysis of morphologic features and molecular subtype was constructed to predict recurrence and refine these traditional prognostic tools.
  
  
  METHODS
  Morphologic features including histologic grade, fibrotic focus, extensive intraductal component, lymphocytic infiltrate, lymphovascular invasion, tumor necrosis, tumor margin and TNM stage, and molecular subtypes approximated by immunohistochemistry were analyzed in 633 patients with invasive breast carcinoma (excluding those with HER2 targeted therapy). Significant independent predictors for recurrence included: high histologic grade (p = 0.004), presence of lymphovascular invasion (p = 0.004), fibrotic focus (p = 0.020), mild lymphocytic infiltrate (p = 0.013), high TNM stage (p < 0.001), and HER2-overexpressing (p = 0.004) and basal-like (p < 0.001) molecular subtypes. A morphologic-molecular recurrence predictive model based on these features was useful in recurrence prediction, independent of treatment modalities, and was able to refine the traditional prognostic tools of histologic grade, TNM stage, and Nottingham prognostic index, particularly for intermediate-risk groups, and to refine the luminal group molecular subtypes. Such findings were reproducible with a validation cohort.
  
  
  CONCLUSIONS
  TNM stage, histologic grade, lymphovascular invasion, fibrotic focus, mild lymphocytic infiltrate, HER2-overexpressing and basal-like molecular subtypes were important independent recurrence risk factors for breast cancer. This morphologic-molecular model was robust in recurrence prediction and refined recurrence risk stratified by the traditional prognostic parameters, independent of treatment modalities.
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yun-Bi
authors.initials: YB
authors.lastname: Ni
authors.forename: Julia Y S
authors.initials: JY
authors.lastname: Tsang
authors.forename: Siu Ki
authors.initials: SK
authors.lastname: Chan
authors.forename: Gary M
authors.initials: GM
authors.lastname: Tse
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D002280:Basal Cell Carcinoma / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000401:mortality / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008875:Middle Aged; D015233:Models, Statistical; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone