Pathologic Evaluation of Triple-Negative Breast Cancer

  • Chad A. Livasy


Triple-negative breast cancer (TNBC) is defined as an invasive mammary carcinoma lacking clinically significant expression of the three most commonly targeted biomarkers in the treatment of breast cancer: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBCs account for approximately 15–20% of all breast cancer diagnoses. The definition of TNBC has been standardized with the publication of national guidelines on ER, PR, and HER2 testing/reporting by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP). Accurate pathologic assessment of tumor ER, PR, and HER2 status is an essential part of classifying tumors into this subset. As a group, these tumors are associated with an aggressive natural history including increased risk for early visceral recurrence and worse disease-specific outcomes compared with other breast cancer subtypes. Tumor morphologic features associated with triple-negative status include Nottingham grade 3 with high mitotic rate, pushing border of invasion, geographic tumor necrosis, lymphocytic infiltrate, large central acellular zone, metaplastic features, salivary gland differentiation, and apocrine differentiation. Not all TNBCs are associated with an unfavorable prognosis, drawing attention to the heterogeneity of this tumor group and the continued need to link tumor histologic subtype and grade with triple-negative status. Gene expression profile studies have identified multiple subtypes of TNBC, including basal-like and claudin-low/mesenchymal-like. Other molecular and pathologic studies of TNBC have identified biologic features in a subset of these tumors with potential therapeutic implications including inactivation of the BRCA pathway, increased tumor-infiltrating lymphocytes (TILs), detection of immune gene signatures including increased PD-L1 expression, and androgen receptor expression. The following review will focus on the pathologic classification, biologic diversity, histopathology, and immunohistochemistry of TNBCs.


Breast cancer Triple-negative Basal-like Estrogen receptor Tumor-infiltrating lymphocytes BRCA1 


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PathologyCarolinas HealthCare SystemCharlotteUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of North Carolina at Chapel HillChapel HillUSA

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