Breast

Ki67 breast


Editorial Board Member: Kristen E. Muller, D.O.
Deputy Editor-in-Chief: Gary Tozbikian, M.D.
Anas Mohamed, M.D.
Joseph Geradts, M.D.

Last author update: 9 May 2022
Last staff update: 9 May 2022

Copyright: 2022, PathologyOutlines.com, Inc.

PubMed Search: Ki67

Anas Mohamed, M.D.
Joseph Geradts, M.D.
Page views in 2022: 2,266
Page views in 2023 to date: 303
Cite this page: Mohamed A, Geradts J. Ki67 breast. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastKi67.html. Accessed February 3rd, 2023.
Definition / general
Essential features
Terminology
  • MIB1 is not equivalent to Ki67; rather, it is a widely used monoclonal antibody against the Ki67 antigen (Breast Cancer 2020;27:1058)
Pathophysiology
  • Anti-Ki67 antibody binds Ki67 protein in formalin fixed paraffin embedded tissue block and highlights nuclei of all cells in nonresting cell cycle phases (Pathology 2017;49:166)
  • Increased expression in tumor cells is a marker of cell cycle activation and proliferative activity
  • Ki67 often is heterogeneously expressed in breast carcinomas, with hot spots and inactive areas (J Natl Cancer Inst 2013;105:1897)
Clinical features
Interpretation
Uses by pathologists
  • As an independent prognostic marker to predict disease free survival, overall survival and complete pathologic response to neoadjuvant chemotherapy
  • Subtyping ER positive breast carcinomas into 2 prognostically distinct subtypes:
    • Luminal A (low Ki67 index; better prognosis)
    • Luminal B (high Ki67 index; worse prognosis) (Mod Pathol 2014;27:554)
  • Ki67 IHC MIB1 pharmDx has been approved by the FDA as a companion diagnostic for detecting Ki67 expression in patients with high risk breast cancer who may be eligible for treatment with abemaciclib combined with endocrine therapy
    • FDA approval of abemaciclib was restricted to patients at high risk of recurrence and with a Ki67 score ≥ 20%, as determined by an FDA approved test; however, restricting the approval to patients with a high Ki67 and the 20% cutoff is debated (Ann Oncol 2022;33:234)
Prognostic factors
Microscopic (histologic) images

Contributed by Anas Mohamed, M.D. and Joseph Geradts, M.D.
Lobular carcinoma, low proliferation

Lobular carcinoma, low proliferation

Lobular carcinoma, low Ki67

Lobular carcinoma, low Ki67

Ductal carcinoma, low proliferation

Ductal carcinoma, low proliferation

Ductal carcinoma, low Ki67

Ductal carcinoma, low Ki67


Ductal carcinoma, intermediate proliferation

Ductal carcinoma, intermediate proliferation

Ductal carcinoma, intermediate Ki67

Ductal carcinoma, intermediate Ki67

Ductal carcinoma, high proliferation

Ductal carcinoma, high proliferation

Ductal carcinoma, high Ki67

Ductal carcinoma, high Ki67

Positive staining - normal
Positive staining - disease
  • Low Ki67 index is observed in benign breast tumors, luminal A carcinomas, low grade ductal carcinomas, lobular carcinomas and tubular carcinomas
  • High Ki67 index is observed in triple negative breast carcinomas, including metaplastic and medullary carcinomas, HER2 positive carcinomas, luminal B carcinomas, high grade carcinomas and pleomorphic lobular carcinomas (BMC Res Notes 2019;12:605)
Sample pathology report
  • Right breast, core needle biopsy:
    • Invasive ductal carcinoma, grade 2
    • Ki67 index: 5% (low)

  • Left breast, total mastectomy:
    • Invasive mammary carcinoma with medullary pattern
    • Ki67 index: 40% (high)
Board review style question #1
Which of the following breast neoplasms is most likely to be associated with an elevated Ki67 labeling index?

  1. Invasive ductal carcinoma, grade 1
  2. Invasive lobular carcinoma, classic type
  3. Metaplastic carcinoma
  4. Tubular carcinoma
Board review style answer #1
C. Metaplastic carcinoma. High Ki67 index is observed in triple negative breast carcinomas, including metaplastic and medullary carcinomas, as well as HER2 positive carcinomas, luminal B carcinomas, high grade carcinomas and pleomorphic lobular carcinomas (BMC Res Notes 2019;12:605).

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Reference: Ki67 breast
Board review style question #2

Which of the following breast tumors is likely to demonstrate a Ki67 labeling index similar to the one shown in the picture?

  1. Invasive cribriform carcinoma
  2. Invasive ductal carcinoma, grade 3
  3. Medullary carcinoma
  4. Pleomorphic lobular carcinoma
Board review style answer #2
A. Invasive cribriform carcinoma. Low Ki67 index is observed in benign breast tumors, luminal A carcinomas, low grade ductal carcinomas, lobular carcinomas and tubular carcinomas and lower grade breast cancer subtypes, such as invasive cribriform carcinoma (BMC Res Notes 2019;12:605).

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Reference: Ki67 breast
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