Cancer as a disease-breast cancer Flashcards
Why does high dose therapy with synthetic oestrogens cause breast tumour regression in post-menopausal women with breast cancer?
High-dose therapy overstimulates the hormonal system leading to downregulation of ER so the cells are no longer responsive to oestrogen
Name an important ER receptor blocker.
Tamoxifen
What specific type of breast cancer accounts for almost 80% of breast cancers?WHAt does it mean.
Infiltrating ductal carcinoma. Means it’s the most common form of ER+ breast cancer? Since ER+ accounts of 80%
What are three methods of ovarian ablation?
Surgical oophorectomy ,Ovarian irradiation, LHRH agonist
State some risk factors for breast cancer.
Early age of onset of menstruation Late age to menopause Age to first full-time pregnancy Some contraceptive pills Some HRT, obesity , diet
What percentage of breast cancers is ER positive?
80%
At what point during the menstrual cycle is oestrogen at its highest?
End of the follicular phase
Where do the vast majority of breast cancers originate?
In the luminal epithelium of the breast (> 90%)
What happens when oestrogen binds to ER?
The oestrogen binds to ER and then two ERs dimerise and translocate to the nucleus (with oestrogen bound) The dimer then binds to response elements in the DNA sequence and regulates transcription
What is raloxifene?
A SERM – it is oestrogenic in bone and anti-oestrogenic in the breast and uterus
What are the problems associated with the methods of ovarian ablation?
two of them(oophorectomy and ovarian irradiation) are irreversible
Describe a reversible and reliable medical ovarian ablation technique.
LHRH agonists bind to LHRH receptors in the pituitary leading to receptor downregulation and suppression of LH release and inhibitionof ovarian function, including oestrogen production
How do post-menopausal women make oestrogen?
Aromatisation of androgens in the fat , liver and muscles . Production in ovaries(no aromatisation here) has topped,
Describe the two layers of epithelial cells in the mammary gland.
Luminal epithelium- inner. Myoepithelium- outer,contractile
How does the presence of ER affect prognosis
GOOD prognosis in women Worse prognosis in male breast cancer
What are three methods of reducing oestrogen action in the breast?
Ovarian suppression Blocking oestrogen production by enzymatic inhibition Inhibiting oestrogen responses
What are the problems associated with tamoxifen?
Increased incidence of endometrial cancer (oestrogenic in the uterus) Increased risk of stroke, DVT, cataracts
What is special about the breast as an organ?
It is the only organ that develops after birth
What type of oestrogen is produced in aromatisation?
Oestrone
What are the two types of aromatase inhibitor?
Suicide inhibitors Competitive inhibitors
Where are oestrogen receptors expressed in the breast?
They are ONLY expressed by luminal cells But not all luminal cells express oestrogen receptors (only about 10-15%
