Molecular subtypes of breast cancer

There are many different types of breast cancer. Some are slow growing and "well behaved" while others are much more aggressive. Traditional pathology reporting describes the cancer by the appearance of the cells under the microscope as ductal / lobular or special type. This appearance does not however reliably predict the behaviour of the tumour.  Recent advances in pathology have allowed a much more detailed analysis of the structure of the cancer cells at a molecular level.

Using these methods researchers have identified four main groups of breast cancer.

Subtype

Molecular features

Prevelance

Luminal A

ER+, +/-PR+,HER2 - , lowK67

40%

Luminal B

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

20%

Basal

ER-, PR-, HER2-,cytokeratin5/6+

15%

HER 2 type

ER-,PR-, HER2+

15%

Normal breast like

Cancers that cannot be satisfactorily classified in 4 groups above

10%

 

Luminal A

The cancer cells look similar to the ductal cells on the inside lining of the breast ducts. (the lumen of the duct is the space inside and the luminal cells are the layer of cells closest to this surface)These tumours appear to have the best prognosis. Treatment can include hormonal manipulation as they are receptor positive.

Luminal B

These tumours have a poorer prognosis and tend to occur in younger women.

Basal like tumours

These tumours have cells that look more like the cells on the outer layer of the duct lining. Most contain p53 mutations. Most basal tumours are triple negative which means that the cells do not express the oestrogen, progesterone or HER2 receptors. Treatment options are limited as we cannot use anti-oestrogen drugs like Tamoxifen or the Aromatase Inhibitors. Herceptin is also of no use in this situation. The medical oncologists will plan systemic treatment using chemotherapy drugs. There is a lot of research interest in newer drugs for this group of cancers.

PARP inhibitors

Targets for therapy - EGF receptor ,aB-crystallin and cyclin E.

HER2 type

These have a poorer prognosis and are associated with higher risk of early recurrence and metastases.

Triple Negative Breast Cancer

10 - 20% of breast cancers do not express the oestrogen, progesterone or HER2 receptors and are consequently referred to as triple negative tumours. The majority have a basal phenotype.  As cell receptors are absent, endocrine therapy with Tamoxifen or Aromatase inhibitors will not be effective. Neither will Herceptin. This means that the medical oncologist must plan treatment using conventional chemotherapy drugs.

Common drugs that are used include doxorubicin (Adriamycin) Epirubicin and Cyclophosphamide. Fluorouracil is often added to this combination (FEC) A Taxane Paclitaxel (Taxol) or  docetaxol (Taxotere) may be prescribed  after  FEC.

Initial treatment will usually consist of surgery (breast conserving partial mastectomy or mastectomy) depending on size and multifocal nature of tumour. Chemotherapy will start approximately  2 -3 weeks after surgery and usually lasts for 4 - 6 months . This may be followed by radiotherapy.

There is a lot of research interest in newer drugs that may be effective in triple negative tumours

PARP inhibitors

(Poly ADP ribose polymerase)In normal cells  PARP repairs damaged DNA. Overactivity of PARP in cancer cells may increase cancer cell growth. PARP inhibitors can prevent cancer cells repairing themselves. Clinical trials are underway to  assess efficacy in Triple negative cancers.

Antiangiogenic agents

Drugs that inhibit blood vessel growth to the cancer will restrict its growth. They act by blocking the vascular endothelial growth factor receptor (VEGFR inhibitors)

DNA damaging drugs

Platinum based medicines that interfere with  DNA building blocks.

 

 

Because of the unique features of triple negative tumours and limited efficacy of existing treatments special interest groups have evolved to provide support and up to date information to patients and their families about new developments and treatment trials.

Living beyond breast cancer     http://www.lbbc.org/

Triple Negative Breast Cancer  http://www.tnbcfoundation.org/tnbcguide.htm

 
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Meet the Surgeon

Trevor Smith MBChB FCS

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