Organ Systems, Breast

Breast – Invasive Carcinoma

Invasive Breast Carcinoma
  • Invasive breast carcinomas not segregated out as a special subtype are classified as invasive ductal carcinoma, no special type (NST).  These tumors (and most of the special types) have prognosis and treatment plans based on the receptor status (and sometimes additional molecular profiling).
  • Receptor testing includes ER/PR/Her-2 and Ki-67 (proliferation marker)

  • ER-positive/Her-2 negative
    • 50-65% of cancers, “Luminal” subtype
    • Further subdivided based on proliferation rate
      • ER positive/Her-2 negative, low proliferation
        • 40-55% of cancers
        • gene profiling dominated by genes regulated by estrogen receptor
        • Typically detected at earlier stage
        • When tumors metastasize, typically after a long period of time and goes to the bone
        • Respond well to hormonal therapy
        • Recurrences can occur after long periods of time (>10 years), often good response to hormonal therapy
      • ER positive/Her-2 negative, high proliferation
        • 10% of cancers
        • ER expression may be low, and PR may be low or negative
        • Most common subtype associated with BRCA2 mutation
        • Gene profiling shows more genes associated with proliferation
        • 10% show a complete response to chemotherapy 
  • Her-2 positive
      • 20% of cancers
      • 50% ER+ (often low), PR (often negative)
      • Subtype charateristic of TP53 mutation (Li-Fraumeni syndrome), Her-2+/ER+
      • Tumors can metastasize when small and sub-clinical
      • Responsive to trastuzumab (Herceptin), especially in the neoadjuvant setting
      • Recurrences usually occur <10 years, not typically responsive to therapy
  • ER-negative/Her-2 negative
    • 15% of cancers
    • Subtype associated with BRCA1 mutations
    • Associated with a basal-like gene profile
    • 30% may show complete response to chemotherapy
    • Recurrences typically occur within 5 years, not typically responsive to therapy
  • Gene expression profiling (GEP) has shown unique characteristics of invasive tumors.  Many share overlap with receptor categories (e.g. Basal-like GEP with triple negative tumors).  However, these are not mutually exclusive, and there is overlap between categories within unique GEP.
    • 10% of basal-like cancers are ER+
    • 15% of basal-like cancers are Her-2+
  • Lymphovascular Invasion
    • Present in 1/2 of invasive tumors (associated with increased risk of LN metastasis)
    • Poor prognostic factor in LN negative patients, and a risk factor for local recurrence
  • Special Subtypes of Breast Carcinoma
References

Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015.