Breast
Breast cancer
Molecular subtypes
Author: Monika Roychowdhury, M.D.
Last author update: 1 August 2012
Last staff update: 22 November 2022 (update in progress)
Copyright: 2001-2023, PathologyOutlines.com, Inc.
PubMed search: luminal [title] phenotype carcinoma breast
Table of Contents
Definition / general | Basal-like | Luminal subtype | Microscopic (histologic) images | Positive stains | Additional referencesCite this page: Roychowdhury M. Molecular subtypes. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmolecularsubtypes.html. Accessed April 1st, 2023.
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
- "Basal like" because tumors have high expression of genes characteristic of basal epithelial cells of normal mammary gland, including CK 5 / 6, CK14, CK15 and CK17
- Not rigidly defined, usually positive for CK5 / 6, CK14 or CK17, and triple negative (ER-, PR-, HER2-), often positive for EGFR
- Original definition based on gene expression profile (Nature 2000;406:747, Proc Natl Acad Sci USA 2001;98:10869)
- Generally considered to not be comparable to triple negative tumors by immunostains (Clin Cancer Res 2008;14:1368, Med Mol Morphol 2009;42:128), but see Breast Cancer Res 2007;9:R65
- Classification of particular tumors may vary based on which classification system is used (Hum Pathol 2008;39:506)
- Tumors are clinically heterogeneous
- 15% of all invasive ductal carcinoma NOS (Breast Cancer 2010;17:118), higher percentage (26% - 30%) of CNS metastases or primaries that metastasize to CNS (Mod Pathol 2007;20:864); higher percentage (34%) in Africa (APMIS 2007;115:1391)
- Basal-like expression also present in 17% of infiltrating lobular carcinoma based on CK5 / 6 expression, these cases are more likely to be ER- (Hum Pathol 2008;39:331)
- Associated with younger age, African-American women, high grade tumors, metaplastic subtype (Mol Cancer Ther 2008;7:944), medullary subtype (Breast Cancer Res 2007;9:R24), high stage, angiolymphatic invasion, BRCA1 (Oncogene 2006;25:5846)
- Not a common subtype in men (Breast Cancer Res 2009;11:R28)
- Of academic interest, not currently used clinically (Arch Pathol Lab Med 2009;133:860); may not be a distinct clinical entity (Pathobiology 2008;75:119, J Biophotonics 2012;5:345)
- Associated with epithelial-mesenchymal transition, defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype (Cancer Res 2008;68:989)
- Poorer survival if express CK 17 or CK 5 / 6 (Am J Pathol 2002;161:1991), CK 5 / 6 or EGFR (BMC Cancer 2007;7:134), HER2+ (not common, Hum Pathol 2008;39:167)
- 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)
Contributed by Dr. Semir Vranic
H&E
Central necrosis
40x
Inflammatory response, periphery
ER negative
CK5/6
CK7
CK14
S100
Images hosted on other servers:
H&E and CK14
p16+
Sheet-like growth and high Ki67 index
Tumor without sheet-
like growth but with
high Ki67 index
Various images
Various immunostains
Normal breast:
CK5 and CK14
CAM 5.2 (CK 8 / 18)
stains luminal epithelium,
CK17 stains basal cells
- Positive stains:
- Usually CK5 or CK5 / 6 (CK5 more sensitive, Am J Clin Pathol 2008;130:724), CK14 or CK17
- Ki67 (high labeling index)
- Often EGFR, IGF-IR or c-kit / CD117
- CD109 (60%, Pathol Int 2008;58:288), laminin 5 (96%, Am J Surg Pathol 2008;32:345), vimentin (55% - 90%), p16 (Am J Surg Pathol 2009;33:163)
- Note: basoluminal variant may be HER2+ and only partially positive for CK5 / 14 (Clin Cancer Res 2006;12:4185)
- Negative stains:
- p53 mutations (Cancer Res 2009;69:663)
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
Additional references
