Clinical and Pathologic Characteristics of Triple Negative Breast Cancer (TNBC)

  • TNBCs:
    • Present with rapid growth
    • Are more likely to be diagnosed clinically rather than mammographically than ER-positive cancers
    • Are more likely to be diagnosed as interval cancers between mammograms:
      • However, intrinsic differences in the density of breast tissue among women diagnosed with TNBC may also explain these differences in presentation
  • Pathologic characteristics:
  • TNBC are usually:
    • High grade
  • The most common histology is:
    • Infiltrating ductal carcinoma:
      • Although a rare histologic subtype:
        • Medullary carcinoma:
          • Is generally triple negative
  • TNBCs can exhibit geographic necrosis, a pushing border of invasion, and a stromal lymphocytic response (Table)
Immunophenotypic and pathologic features of triple negative breast cancer
  • An uncommon subgroup of TNBCs:
    • Is defined histopathologically as metaplastic:
      • However, this is a diverse group of cancer types ranging from squamous to stromal in nature
  • By definition:
    • TNBC lacks immunohistochemical (IHC) expression of the:
      • ER, PR, and HER2
    • Since these three biomarkers represent the only known approved targets for breast cancer treatment:
      • Considerable effort has been made to better understand other biologic forces driving TNBC
  • Molecular classification of TNBC:
    • The triple-negative clinical phenotype:
    • Mostly comprises the basal-like molecular subtype:
      • Although triple-negative and basal breast cancers are not synonymous and there is substantial heterogeneity within TNBCs:
    • As examples, in one study of utilizing DNA and RNA profiling of TNBCs:
      • Four stable subtypes were identified:
        • Luminal androgen receptor
        • Mesenchymal
        • Basal-like immunosuppressed
        • Basal-like immune-activated
    • In another study, 172 triple-negative tumors based on IHC staining were correlated with gene expression profiles that defined the basal subtype:
      • Only 71% of TNBCs were assigned the basal subtype
    • In a converse analysis (where subtype was identified and correlated with IHC staining) of 160 tumors:
      • 77% of basal tumors were triple negative by IHC
    • Other evidence from copy number variation and mutational analyses has also suggested wide variability and breadth of clonal spectra in TNBC
  • Basal breast cancer:
    • Is characterized by the genomic expression of the “basal cluster,”:
      • A unique cluster of genes that includes the epidermal growth factor receptor (EGFR, also called HER1), basal cytokeratins 5/6, c-Kit, the proliferation cluster, and low expression of the hormone receptor- and HER2-related genes
    • Separate subtypes of TNBC have been characterized by gene expression, including:
      • Two basal-like subtypes (BL1 and BL2)
      • Immunomodulatory
      • Mesenchymal
      • Mesenchymal stem-like
      • Luminal androgen subtypes
      • Additional subtypes that have been characterized include:
        • Claudin-low
        • Interferon-rich subtypes
  • Gene expression analysis:
    • Has also revealed that the tumor suppressor gene p53 (TP53) and several DNA repair genes:
      • Particularly the breast cancer susceptibility genes (BRCA):
        • Are either mutated or aberrantly expressed in TNBC
          • These molecular features may have implications for chemotherapy sensitivity to platinum and other directly DNA-damaging agents
  • Taken together, these studies have produced mixed results with varying conclusions among the different investigators:
    • None has reached the level of providing clinical considerations at present
#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #MountSinaiMedical #MSMC #Miami #Mexico #BreastCancer #TripleNegativeBreastCancer

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