Endocrine Related Cancer: Breast Flashcards
(42 cards)
where are the lobules of the breast?
they branch out from the nipples
what does each lobule have?
tiny hollow sacs – alveoli
what links the lobules?
ducts
where is adipose tissue found in the breast?
Space around lobules and ducts is adipose tissue, ligaments and connective tissue (stroma)
which is the main oestrogen type found during pregnancy?
estriol
which is the main oestrogen type found in women of child bearing age?
estradiol
what type of oestrogen is made in the body after menopause?
estrone
what is oestrogen essential for?
growth and function of the normal breast
what happens if there are supraphysiological levels of oestrogen?
selectively kill ER+ve cells
what happens if there are high levels of oestrogen?
High oestrogen, unless opposed by high progesterone, can cause uterine cancer
where does oestrogen have impact?
- female reproductive system (breast/endometrium)
- prostate (& male reproductive system)
- bone (anabolic)
- immune system
- neurones
- pancreatic beta cells
- cardiovascular system
- skin including melanocytes
what do oestrogen receptors bind?
17b-estradiol
how can oestrogen signalling occur?
- Via ERa and classical ERE (slow)
- Via ERb and classical ERE (slow)
- Via ERa and ERa heterodimers (slow)
- Via membrane receptors (rapid)
- Via intracellular (ERb) and other transcription factors via AP1 sites and NOT ERE
how do endocrine therapies to breast cancer work?
All target the estrogen receptor (ER) in some way
which patients is tamoxifen most effective on?
patients who are both ER and PR positive compared to those who are just ER positive but PR negative
what is % of reduction in patients who are ER and PR positive?
53% reduction and risk of recurrence of patients who are both ER and PR positive
what is % of reduction in patients who are only ER positive?
23% reduction who are only ER positive
what are selective oestrogen receptor modulators (SERMS)?
Lack the steroid structure of estrogens but possess a tertiary structure - allows them to bind to the ER
what are the effects of SERMS
- Differential ER expression in a given target tissue
- Differential ER conformation on ligand binding
- Differential recruitment of co-regulator proteins
what are examples of SERMS?
- Tamoxifen
- Used to treat breast cancer since 1970s
- Raloxifene
- licensed by FDA 1997 - osteoporosis
what are the SERMS in breast?
antiestrogen Binds to ER - incorrect conformational shape - unable to bind tissue-specific coactivators
what SERM is found in the endometrium?
estrogen Binds to ER - activates estrogen regulated genes
how do ER mediate gene transcription?
ER mediates gene transcription via AP-1 enhancer element & transcription factors Fos and Jun
what are the benefits of tamoxifen?
- 5 yr therapy of tamoxifen reduces the risk of recurrence and death TWICE as much as 2yr therapy
- While taking tamoxifen 1 out of 2 recurrences and 1 out of 3 deaths are avoided by the therapy
