Cancer as a disease-breast cancer

Question 1

Why does high dose therapy with synthetic oestrogens cause breast tumour regression in post-menopausal women with breast cancer?

Answer 1

High-dose therapy overstimulates the hormonal system leading to downregulation of ER so the cells are no longer responsive to oestrogen

Question 2

Name an important ER receptor blocker.

Answer 2

Tamoxifen

Question 3

What specific type of breast cancer accounts for almost 80% of breast cancers?WHAt does it mean.

Answer 3

Infiltrating ductal carcinoma. Means it’s the most common form of ER+ breast cancer? Since ER+ accounts of 80%

Question 4

What are three methods of ovarian ablation?

Answer 4

Surgical oophorectomy ,Ovarian irradiation, LHRH agonist

Question 5

State some risk factors for breast cancer.

Answer 5

Early age of onset of menstruation Late age to menopause Age to first full-time pregnancy Some contraceptive pills Some HRT, obesity , diet

Question 6

What percentage of breast cancers is ER positive?

Answer 6

80%

Question 7

At what point during the menstrual cycle is oestrogen at its highest?

Answer 7

End of the follicular phase

Question 8

Where do the vast majority of breast cancers originate?

Answer 8

In the luminal epithelium of the breast (> 90%)

Question 9

What happens when oestrogen binds to ER?

Answer 9

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

Question 10

What is raloxifene?

Answer 10

A SERM – it is oestrogenic in bone and anti-oestrogenic in the breast and uterus

Question 11

What are the problems associated with the methods of ovarian ablation?

Answer 11

two of them(oophorectomy and ovarian irradiation) are irreversible

Question 12

Describe a reversible and reliable medical ovarian ablation technique.

Answer 12

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

Question 13

How do post-menopausal women make oestrogen?

Answer 13

Aromatisation of androgens in the fat , liver and muscles . Production in ovaries(no aromatisation here) has topped,

Question 14

Describe the two layers of epithelial cells in the mammary gland.

Answer 14

Luminal epithelium- inner. Myoepithelium- outer,contractile

Question 15

How does the presence of ER affect prognosis

Answer 15

GOOD prognosis in women Worse prognosis in male breast cancer

Question 16

What are three methods of reducing oestrogen action in the breast?

Answer 16

Ovarian suppression Blocking oestrogen production by enzymatic inhibition Inhibiting oestrogen responses

Question 17

What are the problems associated with tamoxifen?

Answer 17

Increased incidence of endometrial cancer (oestrogenic in the uterus) Increased risk of stroke, DVT, cataracts

Question 18

What is special about the breast as an organ?

Answer 18

It is the only organ that develops after birth

Question 19

What type of oestrogen is produced in aromatisation?

Answer 19

Oestrone

Question 20

What are the two types of aromatase inhibitor?

Answer 20

Suicide inhibitors Competitive inhibitors

Question 21

Where are oestrogen receptors expressed in the breast?

Answer 21

They are ONLY expressed by luminal cells But not all luminal cells express oestrogen receptors (only about 10-15%