Breast cancer

Triple negative breast cancer

Editorial Board Member: Julie M. Jorns, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Joshua J.X. Li, M.B.Ch.B.

Last author update: 25 January 2021
Last staff update: 10 March 2023

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PubMed Search: Triple negative breast cancer

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Joshua J.X. Li, M.B.Ch.B.
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Cite this page: Li JJX, Tse GM. Triple negative breast cancer. website. Accessed October 3rd, 2023.
Definition / general
  • Breast cancers with absence of estrogen receptor (ER), progesterone receptor (PR) and HER2 immunohistochemistry (IHC) expression
Essential features
  • Defined by absence of ER, PR and HER2 expression by IHC
  • Overlaps with basal-like breast cancers, which are defined by gene expression profiling
  • Generally associated with high stage on presentation, increased risk of recurrence and shorter survival
  • Highly variable histology, including invasive ductal, metaplastic and medullary
  • A small subset is low grade, comprising mostly rare salivary gland type tumors and variants of metaplastic carcinomas (fibromatosis-like metaplastic carcinoma, low grade adenosquamous carcinoma); this subset is associated with good prognosis concordant to low grade carcinomas
  • Considerable overlap with basal-like breast cancers but not interchangeable
    • Triple negative breast cancers are defined by absence of ER, PR and HER2 expression by IHC
    • Basal-like breast cancers are defined by gene expression profiling
    • ~80% of triple negative breast cancers belong to basal-like breast cancers (Adv Anat Pathol 2020;27:27)
    • Triple negative staining has been advocated as IHC surrogate for molecular basal-like breast cancer in clinical practice
ICD coding
  • No specific ICD code for triple negative breast cancer
  • Breast parenchyma
  • Reproductive / hormonal factors may play a role
  • BRCA1/2 (Breast Dis 2010;32:25)
    • Majority (71%) of breast cancers in BRCA1 carriers
    • 25% of breast cancers in BRCA2 carriers
    • Triple negative breast cancer represents 17% of breast cancers in non-BRCA1/2 carriers
  • Precursor lesion
    • Microglandular adenosis (MGA) or atypical MGA has been postulated to be a potential precursor lesion for some triple negative breast cancers
    • Evidence that some atypical MGA shared similar genomic changes with the associated triple negative breast cancer (more commonly acinic cell carcinoma) (J Pathol 2016;238:677)
Clinical features
  • Microscopic examination of resected tissue that is then tested for ER, PR and HER2
Radiology description
  • Mammography (Acta Radiol 2013;54:889)
    • Hyperdense, oval or lobular masses
    • Indistinct or circumscribed margins
  • Ultrasound (Ann Oncol 2012;23:vi23)
    • Distinct masses with well circumscribed margins
    • Posterior acoustic enhancement occasionally identified
  • Magnetic resonance imaging (Breast J 2013;19:643)
    • Rim and mass enhancement
    • Areas of high intratumoral T2 signal intensity
    • Highest sensitivity among all modalities (Ann Oncol 2012;23:vi23)
Radiology images

Images hosted on other servers:

Enhancement on MRI

Prognostic factors
Case reports
  • Complete surgical excision remains mainstay of curative treatment
  • Neoadjuvant treatment is given for locally advanced disease but also recommended for early (up to pT1cN0M0) disease in triple negative breast cancer (Ann Oncol 2015;26:v8, Eur J Cancer 2020;135:66)
  • Metastatic / advanced / recurrent disease
Gross description
  • Similar gross features to nontriple negative breast cancer
Microscopic (histologic) images

Contributed by Joshua J.X. Li, M.B.Ch.B. and Gary M. Tse, M.B.B.S.

High grade ductal carcinoma

Low grade adenosquamous carcinoma

Squamous cell carcinoma

Carcinoma with medullary features

Triple negative immunophenotype

Virtual slides

Images hosted on other servers:

Fibromatosis-like metaplastic carcinoma

Secretory carcinoma

Medullary carcinoma

Adenosquamous carcinoma

Squamous cell carcinoma

Cytology description
  • Features more likely seen in triple negative breast cancers (Cancer Cytopathol 2012;120:401)
    • Necrotic background, lymphocytes
    • Syncytial clusters
    • Ill defined cell borders
Cytology images

Contributed by Joshua J.X. Li, M.B.Ch.B. and Gary M. Tse, M.B.B.S.

Abundant lymphocytes

Ill defined cell borders

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Left breast, 3 o’clock, needle core biopsy:
    • Invasive ductal carcinoma, grade 3 (glandular differentiation 3, nuclear pleomorphism 3, mitotic rate 3)
    • ER negative (0%), PR negative (0%), HER2 negative (1+) for expression
Differential diagnosis
Board review style question #1

Which of the following is a poor prognostic factor in triple negative breast cancers?

  1. Complete pathologic response to neoadjuvant chemotherapy
  2. Negative nodal status
  3. Presence of rich tumor infiltrating lymphocytes
  4. Presence of central necrosis
  5. Small tumor size
Board review style answer #1
D. Presence of central necrosis. Tumors rich in tumor infiltrating lymphocytes are associated with better survival. Complete pathologic response to neoadjuvant chemotherapy and lower tumor / node stage are all favorable prognostic factors. Centrally necrotizing breast carcinomas have poor prognosis (BMC Cancer 2015;15:282).

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Reference: Triple negative breast cancer
Board review style question #2
Which of the following types of invasive breast carcinoma most likely displays a triple negative immunophenotype?

  1. Encapsulated papillary carcinoma
  2. Invasive cribriform carcinoma
  3. Invasive lobular carcinoma
  4. Invasive papillary carcinoma
  5. Low grade adenosquamous carcinoma
Board review style answer #2
E. Low grade adenosquamous carcinoma. Encapsulated papillary, invasive cribriform and invasive lobular carcinoma commonly and invasive micropapillary carcinoma less commonly show hormone receptor expression. Low grade adenosquamous carcinomas are invariably triple negative.

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Reference: Triple negative breast cancer
Board review style question #3
Which of the following type of triple negative breast cancer is associated with a more aggressive course of disease?

  1. Adenoid cystic carcinoma
  2. Fibromatosis-like metaplastic carcinoma
  3. Low grade adenosquamous carcinoma
  4. Secretory carcinoma
  5. Squamous cell carcinoma
Board review style answer #3
E. Squamous cell carcinoma. Adenoid cystic carcinoma, secretory carcinoma, fibromatosis-like metaplastic carcinoma and low grade adenosquamous carcinoma are considered low grade triple negative breast cancers. Squamous cell carcinoma of the breast is morphologically of a higher grade and associated with a worse prognosis (Hum Pathol 2010;41:679).

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Reference: Triple negative breast cancer
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