Breast Cancer

Question 1

Prevalence of BC

Answer 1

1/5 cancer deaths among women

Question 2

Breast cell lining

Answer 2

Luminal epithelial cells lining walls of ducts
2 layers of epithelial cells :
Inner epithelial cells
Myoepithelial cells (contractile)

Question 3

Differences between lobular, medullary and ductal carcinoma

Answer 3

Lobular: cancer with some architecture to tubes
Medullary: cells packed with neuro endocrine GFs, attract immune cells
Ductal: no distinguishing phenotype most of the time

Question 4

Activation of oestrogen receptor

Answer 4

ERs located in cytosol
Hormone binds to receptor
Migration of receptor into nucleus
Dimerization
Binding to specific DNA sequences 
Cell proliferation increased = BC
Many BCs are ER positive cancers that respond to oestrogen

Question 5

Oestrogen regulated genes and their function

Answer 5

PR - makes cell more responsive to progesterone
C-myc - involved in cell survival, apoptosis
TGF-a - EGF
Cyclin D1 - regulator of cell cycle

Question 6

Treatments for BC

Answer 6

Surgery - masectomy, lumpectomy, lymphadenectomy
RT - following surgery or if tumour too big for surgery
CT - important for ER negative cancers
Endocrine therapy - adjuvant therapy, to prevent relapse

Question 7

What does endocrine therapy target?

Answer 7

Blocks oestrogen production
Inhibits oestrogen response
Ovarian suppression

Question 8

Hormone therapy options

Answer 8

GnRH agonist: receptor down regulation, suppression of LH, inhibition of oestrogen production
Anti oestrogens: (Tamoxifen) competitive inhibitor, targets ER
Aromatase inhibitors: inhibit peripheral conversion of androgens to oestrogen

Question 9

Tamoxifen pharmacokinetics

Answer 9

Selective oestrogen receptor modulator (SERM)
Competitive inhibitor of oestradiol to ER
It is metabolised to form active compound
Recruits co repressor proteins to ER which binds to DNA to modulate gene expression
Causes cell to be held at G1 leading to apoptosis

Question 10

Issues with ER antagonists

Answer 10

Longterm administration can lead to premature osteoporosis

Tamoxifen has oestrogenic effects in bone

Question 11

Side effects of ER antagonists

Answer 11

Thromboembolic episodes
Tamoxifen- endometrial thickening, hyperplasia, fibroids
Cataracts
Deep vein thrombosis

Question 12

2 types of aromatase inhibitors

Answer 12

Suicide inhibitors:
Initially compete with natural substrate for binding to active site of enzyme
Enzyme acts on inhibitor which irreversibly inactivates it
Competitive inhibitors:
Bind reversibly to active site and prevent product formation as long as inhibitor occupies site

Question 13

MOA of progestins

Answer 13

Some are AR antagonists and can be used as anti androgens

Used for uterine and breast cancer at later stage