Background. -Histologic grade, TNM stage, and NottinghamPrognostic 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 1/4 0.004), presence of lymphovascular invasion (p1/4 0.004), fibrotic focu (p1/4 0.020), mild lymphocytic infiltrate (p1/4 0.013), high TNM stage (p > 0.001), and HER2- overexpressing (p1/4 0.004) and basallike (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. Conclusion. -TNM stage, histologic grade, lymphovascular invasion, fibrotic focus, mild lymphocytic infiltrate, HER2-overexpressing and basallike molecular subtypes were important independent recurrence risk factors for breast cancer. This morphologicmolecular model was robust in recurrence prediction and refined recurrence risk stratified by the traditional prognostic parameters, independent of treatment modalities.
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