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Molecular sub-types of Breast Cancer

Molecular markers are the order of the day in most cancers and novel treatments are being developed against these molecular targets. In breast cancer also, these molecular markers not only help in deciding the management but also serve as prognostic markers.

Recently, breast cancer has been divided into four major sub-types:

  • Luminal A
  • Luminal B
  • Triple negative/ basal
  • HER 2 enriched

The following table depicts the molecular profile of these tumors:

Subtype These tumors tend to be

Prevalence (approximate)

Luminal A ER+ and/or PR+, HER2-, low Ki67

40%

Luminal B ER+ and/or PR+, HER2+ (or HER2- with high Ki67)

20%

Triple negative/basal-like

ER-, PR-, HER2-

15-20%

HER2 type ER-, PR-, HER2+

10-15%

ER – estrogen receptor, PR – progesterone receptor

Luminal A tumors:

Most breast cancers are luminal tumors. These tumors resemble the cells lining the mammary ducts and they tend to be:

  • Estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)
  • HER2/neu-negative (HER2-)
  • Low proliferation index (Ki67)
  • Tumor grade 1 or 2

Patients with these tumors express ER, PR receptors and thus are candidates for hormonal therapy (tamoxifen, anastrozole, etc.).

Out of all the four sub-types, luminal A tumors tend to have the best prognosis and low recurrence rates.

 

Luminal B tumors:

Luminal B tumors tend to be:

  • ER+ and/or PR+ (like luminal A tumors)
  • High proliferative index (Ki67) – high number of actively dividing cancer cells
  • Her2/neu positive or negative

Women with luminal  B tumors tend to have a poorer prognosis as compared to patients with luminal A tumors and the tumor characteristics in these patients include:

  • Poorer tumor grade 
  • Larger tumor size
  • Lymph node-positivity

 

Triple negative/basal-like:

Triple negative breast cancers are:

  • ER-
  • PR-
  • HER2-

Characteristic of triple negative tumors:

  • Occur in younger women
  • More common in African American women. Indian studies have also shows a very high rate of triple negative tumors among young Indian women.
  • Aggressive tumors with poor prognosis (worst prognosis among the four sub-types)
  • Increases chances of distant metastasis
  • As these patients are ER, PR negative, they are not candidates for hormonal treatment

These tumors are also referred to as a Basal like tumors and exhibit similar characteristics to tumors found in patients with BRCA 1 gene mutations.

 

HER2 enriched tumors:

HER2 type tumors tend to be:

  • ER-
  • PR-
  • Lymph node-positive
  • Poorer tumor grade
  • HER 2 positive (although 20-30% can be HER 2 negative as well)
  • 75 percent of HER2 type tumors contain p53 mutations
  • Poor prognosis

HER2/neu-positive tumors can be treated with the drug trastuzumab (Herceptin).

 

 

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