Breast Cancer Pathogenesis

  • Mechanisms / Pathophysiology of Breast Cancer:
    • The exact mechanism by which breast cancer is initiated:
      • Is unknown:
        • However, much effort has been made to molecularly characterize breast cancer and delineate its formation and progression
    • At the cell of origin level:
      • The clonal evolution model:
        • In which mutations accumulate
        • Epigenetic changes in tumor cells occur
        • The ‘fittest’ cells survive
      • The cancer stem cell model:
        • In which only the precursor cancer cells:
          • Initiate and sustain progression
            • Cancer stem cells may also evolve in a clonal fashion
    • At the morphological level:
      • There is a continuum of lesions and genetic modifications from normal glands to cancer
  • 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 most frequent histological subtypes of breast cancer include:
            • Invasive lesions:
              • Ductal carcinoma (now referred to as ‘no special type’ (NST))
              • Lobular carcinoma
            • Preinvasive counterparts are:
              • Ductal carcinoma in situ
              • Lobular carcinoma in situ (or lobular neoplasia)
  • The intrinsic subtypes of Perou and Sorlie:
    • Are based on:
      • A 50-gene expression signature:
        • PAM50
  • The surrogate intrinsic subtypes:
    • Are typically used clinically:
      • Are based on:
        • Histology
        • Immunohistochemistry:
          • Looking for the expression of key proteins:
            • Estrogen receptor (ER)
            • Progesterone receptor (PR)
            • Human epidermal growth factor receptor 2 (HER2)
            • The proliferation marker Ki67
      • Tumors expressing ER and / or PR are termed:
        • Hormone receptor-positive
      • Tumors not expressing ER, PR and HER2 are called:
        • Triple-negative
  • At the molecular level:
    • There is evidence showing that breast cancer evolves along two divergent molecular pathways of progression:
      • Mainly related to:
        • ER expression
        • Tumor grade
        • Proliferation:
          • These are described in the intrinsic classification
  • Intrinsic classification (Intrinsic Subtypes PAM50):
    • Basal-like:
      • TP-53 mutations
      • Genetic instability
      • BRCA mutations
      • Medullary-like histology
      • Poorly differentiatied tumors
    • Claudin- low:
      • Largely triple-negative
      • Metaplastic
  • HER2-enriched:
    • HER2 amplification
    • GRB7 amplification
    • PIK3CA mutations
    • TOPO2 and/or MYC amplification
    • NST, pleiomorphic lobular, and micro-papillary histology
  • Normal-like:
    • Artefact:
      • Expression of normal breast components due to low tumour cellularity
  • Luminal B:
    • PI3KCA mutations (40%)
    • ESR1 mutations (30% to 40%):
      • Induced by aromatase inhibitor targeted therapy
    • ERBB2 and ERBB3 mutations
    • NST, micropapillary and atypical lobular histology
  • Luminal A
    • Activation of ERS1GATA3FOXA1XBP1
    • NST, tubular, cribriform, and classic lobular histology
  • Surrogate intrinsic subtypes:
    • Triple-negative:
      • ER negative, PR negative, HER2 negative
      • High grade
      • High Ki67 index
      • NST histology
      • Special type histology:
        • Metaplastic
        • Adenoid cystic
        • Medullary-like
        • Secretory
      • Poor prognosis:
        • Except for some special types
    • HER2-enriched (non-luminal):
      • ER negative, PR negative, HER2 positive
      • High grade
      • High Ki67 index
      • NST histology
      • Aggressive disease:
        • But responds to targeted therapies
      • Intermediate prognosis
    • Luminal B-like HER2 positive:
      • ER positive:
        • But lower ER and PR expression than luminal A-like
      • HER2 positive
      • Higher grade
      • High Ki67 index
      • NST and pleiomorphic
      • Responds to targeted therapies
      • Intermediate prognosis
  • Luminal B-like HER2 Negative:
    • ER positive:
      • But ER and PR expression lower than in luminal A-like
      • HER2 negative
      • Higher grade
      • High Ki67 index
      • High-risk GES (gene expression signature)
      • NST, micropapillary and lobular pleiomorphic histology
      • Intermediate prognosis
    • Luminal A-like:
      • Strongly ER positive and PR positive
      • HER2 negative
      • Low proliferation rates
      • Typically low grade
      • Low Ki67 index
      • Low-risk GES (gene expression signature)
      • NST, tubular, cribriform, and classic lobular histology
      • Good prognosis
  • Rodrigo Arrangoiz MS, MD, FACS cirujano oncology y cirujano de mamá de Sociedad Quirúrgica S.C en el America British Cowdray Medical Center en la ciudad de Mexico:
    • Es experto en el manejo del cáncer de mama.

👉Es miembro de la American Society of Breast Surgeons:


• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016










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