breast cncer Flashcards
incidence/death of breast cancer and why
incidence gone up, but mortality has fallen, due to early diagnosis, chemo/radiotherapy and hormonal therapies
what kind of cancer is breast cancer
carcinoma (epithelial)
DIAGRAM organisation of mammary gland
lumen that carries milk to nipple surrounded by 2 LAYERS of epithelial cells- luminal and myoepithelial (contract luminal cells) cells-
what kind of cell gives shape to the ducts
myoepithelial cells
DIAGRAM progression of normal to malignant breast
luminal epithelial cells proliferate to become benign- they then become either a lobular carcinoma, ductal carcinoma (most common) or medullary carcinoma
major method of staining for carcinoma involving estrogen receptor
using antibodies against human estrogen receptor (HER- carcinoma cells produce this receptor)- most breast cancers are HER POSITIVE
how estrogen receptor stimulated and what kind of receptor it is
nuclear receptor- receptor inactivated by binding to chaperone protein HSB90- estrogen goes into cytoplasm (lipid soluble), binds to receptor to remove HSB90- receptor then combines with another receptor to form a DIMER, which goes into nucleus to stimulate an oestrogen RESPONSE ELEMENT (part of DNA)= switch on genes= cell proliferation
genes switched on by dimer
progesterone receptor, cyclin D1, c-myc
what occurs in breast cancer
oestrogen receptor overexpressed in most breast cancers= excess proliferation
breast cancer in males and effect on treatment
mainly driven by androgens, so treatment involving less oestrogen/blockage not effective
purpose of endocrine therapies
often adjuvant (ie given once surgery done) to prevent any remaining tumour cells from growing
effects of endocrine therapy
inhibition of ovaries, blocking enzymes producing estrogen, or inhibiting response of estrogne
production of estrogen- 2 ways
GNRH to FSH/LH stimulates estrogen ACTH also released to adrenal gland to produce androgens, which are converted into estrogens by aromatase
ppl most affected by breast cancer
POST-menopausal women
ovarian ablation- how done, who for, and problem with these methods
either by surgery, or by radiation- in PRE-menopausal women however it’s iireversible
reversible method of ovarian ablation
GNRH AGONISTS- they overstimulate LHRH/GNRH receptor, downregulating receptors= less LH release= less estrogen
anti-oestrogens- mechanism, main one, what stage cells stuck in
they block response of oestrogen by COMPETITIVELY inhibiting oestrogen receptor- structurally similar, but no efficacy, thus cell stuck in G1 main one TAMOFIXEN, but also fulvestrant
importance of tamoxifen and main side effect
used in POST-menopausal women- hot flushes
issues of post menopausal women and how tamoxifen helps, and thus what is it’s name
post-menopausal higher risk of osteoporosis and CVD due to less estrogen- tamoxifen is ANTAGONIST in breast, but actually estrogen AGONIST in bone and CVS, so reduces risk of these 2 problems- known as SERM (SELECTIVE ESTROGEN RECEPTOR MODULATOR)
main risks of tamoxifen
embolism, potential for endometrial cancer, and cataracts
problem with fulvestrant
is not a SERM, is always anti-estrogenic= increased risk of CVD/osteoporosis
how tamoxifen can be PREVENTATIVE
reduces risk of Contralateral breast cancer (another breast cancer in other mammary gland)
aromatase inhibitors
surpresses OESTRONE production- in adrenal gland in POST-menopausal women, androstenedione/testosteromade- this is then converted to oestrone in fatty tissue ie breast- thus breast produces less oestrone
types of aromatase inhibitors
type 1 are irreversible, type 2 is reversible (competitive inhibition)
enzyme involved in aromatase function
cytochrome P450
progestins in breast cancer
breast cancers that are sensitive to both oestrogen AND progesterone can use this treatment- progestins are given excessively to overstimulate and downregulate receptor
main progestin
megestrol acetate
problems with breast cancer treatment
even though treatment is effective, relapses occurs, so many patients develop metastasis
main risk factor of breast cancer
obesity (androgen conversion often occurs in fatty tissue)
effect of public health programmes
less mortality as cancer caught early
types of breast cancer
estrogen receptor positive and negative
treatment for oestrogen receptor negative breast cancer
chemotherapy
