Cancer 12: Flashcards
what are the major statistics of breast cancer?
- Breast cancer is the leading female cancer, accounting for almost 1 in 5 cancer deaths among women.
- 1 in 8 women in the UK and the USA will develop the disease in their lifetime
- Currently, around 55,000 women develop breast cancer every year in the UK.
- breast cancer incidence has been increasing each year
- breast cancer mortality has been falling each year
why has the mortality of breast cancer decreased?
- chemo and radiotherapies are much better
- earlier diagnosis due to public health message to women to check their breasts
what is special about the breast organ?
- This is the only organ that develops after birth
- During puberty the breast develops into a fatty glandular structure
what is the structure of the breast?
- there is a tubular network of ducts and glands within the breast which comes together at the nipple
what is the phyllodes tumour?
this is a tumor in the fatty stromal area it is a very rare and very aggressive type of tumor
where does the majority of breast cancer originate from?
- The majority of breast cancer (>90%) originates in the luminal epithelium
what is the cellular organization of the mammary gland?
how many layers of epithelial cells?
- Between the tubules, you have fatty stromal cells
- there are two layers of epithelial cells
luminal epithelial cells
myoepithelial cells (surround the luminal cells)
what do the Myoepithelial cells do?
- the myoepithelial cells have a contractile phenotype
- they contract when they receive the correct hormonal signals
- they need to contract so they can force the milk out of the breast
why are myoepithelial cells important?
- Myoepithelial cells are very important in the development of the gland
- They are responsible for the formation of the tubules
- the luminal cells lie passively underneath
what do the luminal epithelial cells do?
- some of the luminal epithelial cells express estrogen receptors (10%-15%)
how do the cells in the breast respond to estrogen?
- in a normal gland the response to estrogen is to stimulate growth
- the oestrogen receptor positive cells do not grow in repsonse to oestrogen
- instead the oestrogen receptor-positive cells produce growth factors that stimulate the growth of nearby cells
what happens to the oestrogen receptor cells in breast cancer?
- the oestrogen receptor cells directly respond to their own signal and stimulate their own growth
what is a precancerous state of the breast cells?
- when there is a proliferation of the luminal cells but the myoepithelium is still around it

what is a lobular carcinoma?
- produce growth factors that stimulate the growth of nearby cells

what is a medullary carcinoma?
- the tumor cells don’t look anything like the epithelial cells from the mammary gland

what are the majority of breast cancers?
- they are nt medullary or lobular they are just breast carcinoma
what is a main histological test carried out on breast tumors?
- stsaining of the tissue samples for the oestrogen receptor is carried out to classify the breast tumors as
- ER-positive
- ER-negative
what is being stained in the test for estrogen receptors ?
- It is the nuclei that are being stained in this test because ER is a transcription factor that is found in the nucleus
what percentage is a positive ER?
80%
what are some risk factors for ER positive breast carcinoma ?
- Early age of onset of menstruation
- Late age to menopause
- Age to first full=term pregnancy
- Some contraceptive pills
- Some HRTs
how does the oestrogen bind to the ER receptor?
what are the effects?
- ER is a cytosolic receptor = inside the cell
- it is bound to a heat-shock protein forming a dimer
- estrogen is very lipophilic and ca pass through the cell membrane
- once inside the cell the estrogen binds to the ER and displaces the heat shock protein
- Two oestrogen receptors then come together to form a dimer, this dimerised protein enters the nucleus and locate DNA sequences in the genome that are response elements for this transcription factor
- the most important target genes of the transcription factor are the following:
Progesterone receptor
Cyclin D1
C - Myc
TGF alpha
- the oestrogen induced gene products result in increased cell proliferation resulting in breast cancer

why is the dimerisation of the ER significant?
- the response elements are present in two halves so each half of the dimer will bind to each half of the response element
how are pre menopausal women with breast cancer treated?
- About 1/3 of PREmenopausal women with advanced breast cancer will respond to oophorectomy
- this is removal of the ovaries
how are post-menopausal women treated?
- breast cancer in post-menopausal women responds to high dose therapy with synthetic estrogens this causes breast tumor regression
- if you overstimulate this hormone system it will result in the downregulation of ER so the cells are no longer responsive to estrogen


