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BREAST CANCER
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Lecture notes of 8 pages for the course Mechanisms of pathology at Aston (IMMUNOLOGY NOTES)
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Breast cancer.Breast organisation and cancer.
Breast tumours which are created are part of the epithelium tissue, which is
secreting the milk and preparing the milk, for females and producing different
substances in males.
There are glands and tissues which are formed in protecting the cells from the
outside world.
The breast anatomy are made of different elements: there are adipose tissues, form
a protective layer all across the breast. Lobules cluster in the centre. Lobules are
connected to one another through the duct. This comes to the anterior part of the
breast with the formation of the nipple and lactiferous sinuses which come to the
outside.
All of the cells have the epithelial cells protecting the lobules and the ducts from the
outside world.
All of the internal things would be exposed to chemicals and whatever is outside.
Breast cancer is an invasive tumour, and it is also a malignant tumour. It is a
carcinoma, but it will either be a ductal carcinoma, if we are looking at the epithelial
cells which form the lumen of the duct. Or it will be a lobular carcinoma, if we are
referring to the epithelial layers, which are forming the space of lobules.
There are two types of potential tumours that we are going to see.
If the tumour is benign, it will be ductal adenoma or ductal carcinoma if they are
invasive.
If the tumour is benign, it will be called lobular adenoma or lobular carcinoma if it is
malignant.
Different types of ductal carcinoma.
The ductal carcinoma, which is part of the ducts, they are the most common one in
terms of the number of cases.
About 80-90% of all breast cancers or benign tumours are ductal in origin, so cells
will be going dysfunctional in the ducts.
The different types of stages the cell will take: It will go from normal cells to
hyperplasia, which will induce the formation of ductal neoplasm which is excessive
proliferation and the early stage of any tumour. This will try and integrate and go
more into the lumen and form an atypical ductal hyperplasia. This will potentially go
and become invasive, and there will be things like an aplasia taking place where the
structure is lost and you will find a ductal carcinoma in situ, it remains in the ducts.
Up to the stage where the basal lamina is still conserved, then infiltration takes
place.
This is where you get the very malignant and invasive metastatic aspect of it.
Invasive ductal carcinoma (IDC) is the most common type of breast cancer it Makes
up 80% of all breast cancers.
L
Different types of lobular carcinoma.
Only found in 10-15% of cases.
, Lobular breast cancer is a type of cancer which originates in the lobules or milk-
producing glands of the breasts. Each breast has 20 lobules. It can happen in any of
the 20 lobules that are formed in there.
The reason why these lobules are less prone to generate tumour cells and cancer
cells than the ducts are, are not necessarily clear.
It could just be because the ducts are closer to the surface and closer to the
environment, so they are in a more protective part of the tissue and will be coping
more with the outside environment.
There could be something related to hormone regulation; however, it is not very
clear.
Some of the oncogenes known.
It is a balance of a protooncogene becoming an oncogene, and it is a balance of the
tumour suppressor gene losing its functions.
The oncogene, they have a dominancy in relation to gain of function on one of the
allele, they are the most likely.
So, this is a more probable way that this is going to be affected.
In context of breast cancer in general, there is a lot of tyrosine kinase, RTK, this is
one of the key aspects in the early stage of the pathway.
Examples of tyrosine kinase receptors.
The tyrosine kinase receptors are vital to a fundamental aspect of 3 different
domains which are key in the regulation of the pathway:
You are expected to get intracellular domain, transmembrane domain and
extracellular domain.
Three different elements are also important: the plasma membrane, is where you
find the anchoring structures of the receptors, and these will be allowing the
degradation in the bi lipid layers.
The extracellular domain part will be important for the recognition of the ligand and
hormones.
Intracellular domain is the one that has the tyrosine kinase domain, which leads to
the phosphorylation of tyrosine residues.
Whether they work as dimers or monomers, whether they have insulin
immunoglobulin like domains, this will depend on the receptors themselves.
Example, the key ones when it comes to breast cancer is the EGF receptors,
epithelial growth factors, and FGF receptor.
These are very important in the progression of the disease.
Growth factor dependence in breast cancer.
These receptors will have the ability to auto phosphorylate, or phosphorylate the
dimer, if they are part of a dimer complex.
This will be achieved only upon binding of the ligand, which will be growth factors.
And then this tyrosine kinase activation will then lead to phosphorylation of other
components. Which will be bound to the receptors when it is in the phosphorylated
stage.
This will trigger further signalling events and signalling molecules, like the RAS
protein.
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