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.
ER+, +/-PR+,HER2 - , lowK67
ER+, +/-PR+, HER2+(or HER2- with high Ki67)
ER-, PR-, HER2-,cytokeratin5/6+
HER 2 type
Normal breast like
Cancers that cannot be satisfactorily classified in 4 groups
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
These tumours have a poorer prognosis and tend to occur in
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.
Targets for therapy - EGF receptor ,aB-crystallin and cyclin
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
(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.
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
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
Living beyond breast cancer http://www.lbbc.org/
Triple Negative Breast Cancer http://www.tnbcfoundation.org/tnbcguide.htm