Cancer 12: breast cancer Flashcards
(37 cards)
How many cancer deaths is breast cancer accountable for?
1 in 5
It is the leading female cancer
Where does a majority of breast cancer originate?
luminal epithelium (>90%)
What is the structure of the mammary gland?
- between tubules you have fatty stromal cells
- epithelial cells line the lumen of the tubules
- there are TWO types of epithelial cell
luminal epithelial cells
myoepithelial cells
What do myoepithelial cells do?
- they have a contractile phenotype and will contract in response to the correct signals
- they are responsible for the formation of tubules
what cell are oestrogen receptors ONLY present on?
-luminal epithelial cells
they respond to oestrogen to stimulate growth in adjacent cells
What happens to the effect of oestrogen receptors in cancer?
the cells directly respond to oestrogen as a growth factor and therefore stimulates their growth
What occurs with a benign tumour?
there is proliferation of luminal cells but there is still myoepithelium surrounding it
it then develops into either LOBULAR CARCINOMA or MEDULLARY CARCINOMA or just a CARCINOMA
What type of carcinoma accounts for almost 80% breast cancers?
infiltrating ductal carcinoma
What type of staining is useful in diagnosing the breast cancer?
immunohistochemical staining using antibodies against the ER
What percentage of breast cancers are estrogen-receptor positive?
about 80%
How does the estrogen receptor lead to breast cancer?
oestrogen binds to the ER inside the cell, two ER come together to form a dimer which is then able to enter the nucleus
- once in the nucleus gene expression is induced by binding to specific DNA sequences called estrogen response elements
- this increases cell proliferation resulting in breast cancer
What are the most important estrogen regulated genes?
- progesterone receptor
- cyclin D1
- c-myc
- TGF-alpha
What therapy’s do pre and post menopausal women respond to?
1/3 premenopaousal women respond to oophorectomy
postmenopausal women respond to high-dose therapy with synthetic estrogens
What are the major treatment approaches on breast cancer?
- surgery
- radiation therapy
- chemotherapy
- endocrine therapy
How is endocrine therapy achieved?
- ovarian suppression
- blocking estrogen production by enzymatic inhibition
- inhibiting estrogen responses
Where does oestrogen come from in pre and post menopausal women?
- in premenopausal women the ovaries are the main site of oestrogne production
- in postmenopausal women aromatisation of androgens in peripheral tissue is the main source
How can ovarian ablation be carried out?
- surgical oophorectomy
- ovarian irradiation
How can reversible ovarian ablation occur?
- luteinising hormone releasing hormone (LHRH) agonist
- this binds to the LHRH receptor leading to a down regulation of the receptors
this suppresses LH release and inhibits ovarian function
Give FOUR examples of LHRH agonists
- goserelin
- buserelin
- leuprolide
- triptorelin
How can aromatase be inhibited?
aromatase inhibitors
prevent the conversion of androgens to oestrogen
Give an example of an anti-estrogen
taxoxifen is a competitive inhibitor
- they negate the stimulatory effects of estrogen by blocking the ER causing it tp be held in the G1 phase
When is tamoxifen chosen as endocrine treatment?
- metastatic disease in postmenopausal patients
- few side effects are reported with hot flushes being the most common
What class of drug is tamoxifen?
SERM - selective estrogen receptor modulator
it is oestrogenic in bone so can help with post menopausal osteoporosis
it is also oestrogenic on the cardiovascular system so can decrease atherosclerosis risk in women
What is tormifene?
-structural derivative of tamoxifen with similar antiestrogenic and estrogenic properties
