Breast Cancer

  • Breast cancer is the most frequent malignancy in women:
    • Is a heterogeneous disease on the molecular level
  • Over the past 10 to 15 years:
    • Treatment concepts have evolved to take this heterogeneity into account:
      • With emphasis being placed on:
        • More biologically-directed therapies and treatment de-escalation to reduce the adverse effects of treatment
      • Despite the inherent molecular heterogeneity, which is a driving principle of modern-day treatments:
        • Some features such as the impact of locoregional tumor burden or metastatic patterns are shared and influence therapy
  • Early breast cancer:
    • That is, cancer that is contained in the breast or that has only spread to the axillary lymph nodes:
      • Is considered curable
      • Improvements in multimodal therapy have led to:
        • Increasing chances for cure in approximately 70% to 80% of patients
    • By contrast, advanced (metastatic) disease is not considered curable using currently available therapeutic options:
      • However, advanced breast cancer is a treatable disease:
        • For which the main goals of therapy are to prolong survival and control symptoms with low treatment-associated toxicity:
          • To maintain or improve quality of life (that is, improved quality-adjusted life expectancy).
  • 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, and several classifications on the basis of molecular and histological characteristics have been developed
  • The histological subtypes described here (top right) are the most frequent subtypes of breast cancer:
    • Invasive:
      • Ductal carcinoma (now referred to as ‘no special type’ (NST)):
        • Develops from:
          • DCIS
        • Fibrous response:
          • To produce a mass
        • Metastasizes via:
          • Lymphatics and blood
      • Lobular carcinoma:
        • Isolated tumor cells:
          • CDH1 mutations
        • Minimal fibrous response
        • Metastasizes preferentially:
          • Via viscera
    • Pre-invasive:
      • Ductal carcinoma in situ:
        • Spreads through ducts and distorts ductal architecture:
          • Can progress to invasive cancer:
            • Unilateral
      • Lobular carcinoma in situ (or lobular neoplasia):
        • Does not distort ductal architecture:
          • Can be bilateral
        • Risk factor rather than precursor
  • The intrinsic subtypes of:
    • Perou and Sorlie are based on:
      • A 50-gene expression signature (PAM50)
    • Basal-like:
      • TP53 mutations
      • Genetic instability
      • BRCA mutations
      • Medullary-like histology
      • Poorly differentiatied
    • Claudin- low:
      • Largely triple-negative
      • Metaplastic histology
    • HER2-enriched:
      • HER2 amplification
      • GRB7 amplification
      • PIK3CA mutations
      • TOPO2 and / or MYC amplification
      • NST, pleiomorphic lobular and micropapillary histology
    • Normal-like:
      • Artefact:
        • Expression of normal breast components:
          • Due to low tumor cellularity
  • The surrogate intrinsic subtypes:
    • Are typically used clinically:
      • Are based on histology and immunohistochemistry 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
    • Triple-negative:
      • 10% to 15% of the cases
      • ER negative, PR negative, HER2 negative
      • High grade
      • High Ki-67 index
      • NST histology
      • Special type histology:
        • Metaplastic
        • Adenoid cystic
        • Medullary-like
        • Secretory
      • Poor prognosis:
        • Except for some special types
    • HER2-enriched (non-luminal):
      • 13% to 15% of the cases
      • ER negative, PR negative, HER2 positive
      • High grade
      • High Ki-67 index
      • NST histology
      • Aggressive disease:
        • But responds to targeted therapies
      • Intermediate prognosis
    • Luminal B-like HER2 Positive:
      • 13% to 15% of the cases
      • ER positive:
        • But lower ER and PR expression than luminal A-like
      • HER2 positive
      • Higher grade
      • High Ki-67 index
      • NST and pleomorphic
      • Responds to targeted therapies
      • Intermediate prognosis
    • Luminal B-like HER2 Negative:
      • 10% to 20% of the cases
      • ER positive:
        • But ER and PR expression lower than in luminal A-like
      • HER2 negative
      • Higher grade
      • High Ki-67 index
      • High-risk gene expression signature (GES)
      • NST, micro papillary and lobular pleomorphic histology
      • Intermediate prognosis
    • Luminal A-like:
      • 60% to 70% of the cases
      • Strongly ER positive and PR positive
      • HER2 negative
      • Low proliferation rates
      • Typically low grade
      • Low Ki-67 index
      • Low-risk gene expression signature (GES)
      • NST, tubular cribriform histology and classic lobular histology
      • Good prognosis

#Arrangoiz #CancerSurgeon #BreastSurgeon #CASO #CenterforAdvancedSurgicalOncology

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