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Pertuzumab


Topic Completed: 24 February 2020

Minor changes: 24 February 2020

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PubMed Search: Pertuzumab[TI] OR Perjeta[TI] pathology free full text[sb]

Y. Albert Yeh, M.D., Ph.D.
Page views in 2020 to date: 129
Cite this page: Yeh YA. Pertuzumab. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/drugspertuzumab.html. Accessed May 29th, 2020.
Definition / general
  • Humanized IgG1 kappa monoclonal antibody targets extracellular domain of HER2 tyrosine kinase receptor
  • Discovered and developed by Genentech, Inc., South San Francisco, CA
  • Synonym: 2C4 (monoclonal antibody)
    • rhuMAb-2C4
Trade name
  • Perjeta®
Pathophysiology
  • HER2, a member of HER family, does not have a receptor specific ligand binding site
  • HER2/neu signaling in cancer cells (N Engl J Med 2007;357:39)
    • HER2 heterodimerizes with HER1, HER3 or HER4, phosphorylates and activates intracellular tyrosine kinase domain
    • The activated tyrosine kinase on HER2 activates PI3K-Akt pathway and induces cellular survival
    • The activated tyrosine kinase activates SOS, induces a cascade of activation of RAS-RAF-MAPK-MEK and MAPK, eventually promotes cellular proliferation
    • Cleavage of HER2 extracellular domain produces phosphorylated P95 that could activate downstream signal transduction
  • Mechanism of action of pertuzumab (Oncology (Williston Park) 2014;28:186)
    • Upon binding the extracellular dimerization subdomain II of HER2, pertuzumab reduces activation of HER2 by disrupting dimerization of HER2 with HER1, HER3 or HER4
  • See Diagrams / tables, figure 7
Diagrams / tables

Images hosted on other servers:

HER2 IHC testing in breast cancer

HER2 single probe ISH in breast adenocarcinoma

HER2 dual probe ISH in breast adenocarcinoma

HER2/CEP17 ≥ 2.0, HER2 < 4 signals/cell

HER2/CEP17
< 2.0, HER2 copy number ≥ 6.0 signals/cell

HER2/CEP17 < 2.0,
HER2 copy number
≥ 4.0 and < 6.0
signals/cell


Mechanisms of action of trastuzumab and pertuzumab

Trastuzumab and pertuzumab comparisons

Clinical information
Uses by pathologists
  • Identify HER2 positive breast adenocarcinomas
    • HER2 testing needed on all newly diagnosed breast adenocarcinomas
    • Metastatic diseases (test performed in a metastatic site)
  • HER2 immunohistochemistry in breast adenocarcinoma (see Diagrams / tables, figure 1)
    • ASCO-CAP HER2 Test 2013 and 2018 Guideline Recommendation (Arch Pathol Lab Med 2014;138:241, Arch Pathol Lab Med 2018;142:1364)
      • Negative (score 0):
        • No staining
        • Incomplete faint membrane staining ≤ 10% invasive tumor cells
      • Negative (score 1+):
        • Incomplete faint membrane staining > 10% invasive tumor cells
      • Equivocal (score 2+): perform HER2 ISH (see Diagrams / tables, figure 2)
        • Incomplete, weak / moderate membrane staining > 10% invasive tumor cells
        • Complete, intense membrane staining ≤ 10% invasive tumor cells
      • Positive (score 3+):
        • Complete, intense circumferential membrane staining > 10% invasive tumor cells
  • HER2 single probe in situ hybridization (ISH) in breast adenocarcinoma (see Diagrams / tables, figure 2)
    • ISH negative (not amplified)
      • Single probe HER2 copy number < 4.0
    • ISH positive (amplified)
      • Single probe HER2 copy number ≥ 6.0 signals/cell
    • ISH equivocal: perform HER2/CEP17 dual probe ISH (see Diagrams / tables, figure 3)
      • Single probe HER2 copy number ≥ 4.0 and < 6.0 signals/cell
  • HER2 dual probe ISH in breast adenocarcinoma (see Diagrams / tables, figure 3)
    • Negative:
      • Dual probe HER2/CEP17 < 2.0, HER2 copy number < 4.0 signals/cell
    • Positive:
      • Dual probe HER2/CEP17 ≥ 2.0, HER2 copy number ≥ 4.0 signals/cell
    • Equivocal (see Diagrams / tables, figures 4, 5 and 6):
      • HER2/CEP17 ≥ 2.0, with HER2 copy number < 4.0 signals/cell (see Diagrams / tables, figure 4)
      • HER2/CEP17 < 2.0, HER2 copy number ≥ 6.0 signals/cell (see Diagrams / tables, figure 5)
      • HER2/CEP17 < 2.0, HER2 copy number ≥ 4.0 and < 6.0 signals/cell (see Diagrams / tables, figure 6)
Side effects
Board review style question #1
    Which of the following drugs target HER2 / neu on cancer cells?

  1. Dabrafenib
  2. Larotrectinib
  3. Pertuzumab
  4. Trametinib
Board review answer #1
C. Pertuzumab

Reference: Pertuzumab

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Board review style question #2
    Which of the following results is interpreted as positive staining (score 3+) for HER2 in breast adenocarcinoma?

  1. Complete, intense basolateral membranous staining > 10% of tumor cells
  2. Complete, intense circumferential membranous staining > 10% of tumor cells
  3. Complete, intense luminal membranous staining > 10% of tumor cells
  4. Complete, intense nuclear and cytoplasmic staining > 10% of tumor cells
Board review answer #2
B. Complete, intense circumferential membranous staining > 10% of tumor cells

Reference: Pertuzumab

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