Pathology of Triple Negative Breast Cancer Part 1

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Definition:
    • Triple negative breast cancer (TNBC) is a subtype of breast tumor lacking hormone receptors expression and HER2 gene amplification:
      • Represents 24 % of newly diagnosed breast neoplasms
    • TNBC is usually characterized by poor prognosis and lack of wide choice therapeutic agents due to the absence of targetable hormone receptors and HER2 expression:
      • Therefore is considered a very interesting and challenging topic for breast cancer research
    • TNBC is a functional term that defines a wide spectrum of entities:
      • With different biology and clinical behavior, with marked genetic, transcriptional, histologic and clinical differences
    • The definition of a new classification for breast cancer based on its gene expression pattern divided breast tumors into four “intrinsic subtypes”:
      • Luminal subtype:
        • Divided in Luminal A and Luminal B:
          • Characterized by estrogen receptor gene expression
      • The HER2 subtype:
        • Characterized by HER2 gene amplification
      • The so-called basal-like subtype:
        • A particular breast cancer showing positivity for basal and myoepithelial markers and lack of hormone receptors and HER2 gene amplification
      • “Normal breast-like” subtype:
        • With triple-negative phenotype but cellular derivation typical of normal breast epithelium
      • Notably, both the basal-like and normal breast-like subtypes were already recognized as triple negative
  • All breast cancers arise in the terminal duct lobular units (the functional unit of the breast) of the collecting duct
  • The histological and molecular characteristics:
    • Have important implications for therapy:
      • Several classifications on the basis of molecular and histological characteristics have been developed
  • The histological subtypes described here (Figure) are the
    most frequent subtypes of breast cancer:
    • Ductal carcinoma (now referred to
      as ‘no special type’ (NST)      ) and lobular carcinoma:
      • Are the invasive lesions
    • Their pre-invasive counterparts are:
      • Ductal carcinoma in situ and lobular carcinoma in situ (or lobular neoplasia), respectively
        • The intrinsic subtypes of Perou and Sorlie:
          • Are based on a 50-gene expression signature (PAM50)
        • The surrogate intrinsic subtypes are typically used clinically and are based on histology and
          immunohistochemistry expression of key proteins          :
          • Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2
            (HER2) and the proliferation marker Ki-67
        • Tumors expressing ER and / or PR are termed ‘hormone receptor-positive’
        • Tumors not expressing ER, PR and HER2 are called ‘triple-negative’
  • The normal breast terminal duct lobular unit:
    • It is formed by two layers:
      • Inner or luminal layer (epithelial cell layer)
      • Outer or basal layer (myoepithelial cell layer)
Cancer can arise from both of this layers
  • Molecular subtypes that are triple negative:
    • Basal-like:
      • TP53 mutations
      • Genetic Instability
      • BRCA mutations
      • Medullary-like histology
      • Poorly differentiated
    • Claudin-low:
      • Largely triple negative
      • Metaplastic
    • Normal breast-like
    • Molecular apocrine
    • Interferon rich
We can classify TNBC according to the grade of the tumor. Representative micrographs of low-grade and high- grade variants of TNBC.
Histologic Types of TNBCs and their key genetic features/potential therapeutic targets.
  • TNBC can be classified into:
    • Low-grade and high-grade histologic types
  • Several histologic types of low-grade TNBC, including:
    • Salivary gland-like tumors of the breast and solid papillary carcinoma with reverse polarity:
      • Are underpinned by specific / pathognomonic genetic alterations
    • In contrast, acinic cell carcinoma and high-grade variants of TNBC have somatic genomic landscape similar to those of conventional TNBC
    • Low- grade variants of metaplastic breast carcinomas (MBCs) are unlikely to be underpinned by specific genetic alterations; however, the genetic analyses performed to date included only a few or single cases
    • Progression to high-grade TNBC has been described in most low-grade forms of TNBC:
      • However, it occurs at a different rate
    • Whereas fairly common in acinic cell carcinoma, it is a rare event in the salivary gland-like tumors of the breast and solid papillary carcinoma with reverse polarity
    • It should be noted that evidence for the presence of PRKD1 E710D mutations or PRKD1/2/3 rearrangements in polymorphous carcinoma of the breast remains to be documented
#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #Surgeon #Doctor #MountSinaiMedicalCenter #MSMC #Miami #Me

Unknown's avatar

Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

Leave a comment