Breast
Breast cancer
Molecular subtypes


Topic Completed: 1 August 2012

Minor changes: 17 September 2020

Copyright: 2001-2019, PathologyOutlines.com, Inc.

PubMed search: luminal [title] phenotype carcinoma breast

Monika Roychowdhury, M.D.
Page views in 2020 to date: 726
Cite this page: Roychowdhury M. Molecular subtypes. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmolecularsubtypes.html. Accessed November 23rd, 2020.
Definition / general
  • Classification is based on gene expression (molecular) profile studies; subtype reflects clustering of genes activated by ER signaling pathways
  • Distribution by molecular typing is: luminal A: 71%; luminal B: 8%; HER2+: 6% basal-like: 15% (Ann Surg Oncol 2009;16:2705)
  • Luminal subtypes include luminal A (ER+ [strong], PR+, HER2-) and luminal B (ER+ [weak / moderate], PR-, sometimes HER2+)
  • Some authors also include categories of luminal A-HER2 and luminal B-HER2 hybrids (Int J Clin Exp Pathol 2009;2:444)
  • Luminal cytokeratins are CK7 / 8, 18 and 19
  • Luminal A and B subtypes are associated with mutations in E-cadherin and MAP2K4, and amplifications of Cyclin D1, HER2 and HDM2 (Breast Cancer Res Treat 2010;121:53)
  • Luminal A breast cancers are usually low grade, with slow growth and better prognosis than luminal B (J Natl Cancer Inst 2009;101:736)
  • Luminal B breast cancers: some are HER2+, but the major biological distinction from Luminal A is the proliferation signature, in which CCNB1, MKI67 and MYBL2 genes have higher expression in luminal B than in luminal A tumors (BMC Genomics 2006 Apr 27;7:96)
  • Luminal A and most grade 1 luminal B (HER2+) cases are low proliferative (Breast Cancer 2014;21:47)
Basal-like
  • High grade or metaplastic morphology, may have medullary features (Am J Surg Pathol 2007;31:501)
  • Also geographic necrosis, pushing borders, stromal lymphocytic response, increased mitotic count
  • Subtypes include pure (negative for S100 and actin) or myoepithelial (S100+ or actin+, Mod Pathol 2007;20:1200)
  • Includes secretory breast carcinomas with ETV6-NTRK3 fusion gene (Mod Pathol 2009;22:291)
  • Core biopsy: solid growth pattern, high nuclear grade, marked lymphocytic infiltrate and geographic necrosis are helpful features, also immunostains (Appl Immunohistochem Mol Morphol 2008;16:411)

Images hosted on other servers:

Various images

H&E and CK14

p16+

Various immunostains

Sheet-like growth and high Ki67 index

Tumor without sheet-
like growth but with
high Ki67 index



Normal breast:

CK5 and CK14

CAM 5.2 (CK 8 / 18)
stains luminal epithelium,
CK17 stains basal cells



Contributed by Dr. Semir Vranic, Sarajevo:

H&E

Central necrosis


40x


Inflammatory response, periphery


ER negative



CK 5/6


CK7


CK14

S100



Various images

Various immunostains

Luminal subtype
  • Defining molecular feature is ER expression
  • Major difference between luminal A and luminal B breast cancers is degree of proliferation and HER2 expression signature, which is more pronounced in luminal B (Breast Care (Basel) 2011;6:258)
Microscopic (histologic) images

Images hosted on other servers:

Classic Luminal A tumor is ER+ (strong), Ki67 low

Uncommonly, Luminal A tumor has high Ki67 index

Positive stains
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