Breast cancer Flashcards
Summarise the epidemiology of breast cancer
- Leading female cancer, almost 1/5 cancer deaths among women
- 1 in 8 women in UK + USA will develop it in their lifetime
- Approx 55,000 women develop breast cancer every year in UK
- Incidence is rising
- Mortality is falling – early diagnosis, chemo/radiotherapies, hormonal therapies
What are the clinical features of breast cancer?
!!! New lump or mass
- Swelling of all or part of a breast (even if no distinct lump is felt)
- Skin irritation or dimpling
- Breast or nipple pain
- Nipple retraction
- Redness, scaliness, or thickening of the nipple or breast skin
- Nipple discharge (other than breast milk)
What are the pathological features of breast cancer?
- Infiltrating ductal carcinoma - no special histological structure = 80% of breast cancers
- ER positive (over 80%) or ER negative
??
How does breast cancer develop?
- Benign/carcinoma in situ - proliferation of luminal cells but myoepithelium is still around it - possible precancerous state
- a Lobular carcinoma - tumour has some resemblance of architecture of gland - tubules of some form
OR - b Medullary carcinoma - tumour cells don’t look anything like epithelial cells from mammary gland
Note: majority of breast cancers aren’t medullary or lobular - just called breast carcinoma
What is the basis of using endocrine therapies used to treat breast cancer?
Breast cancer growth is oestrogen-regulated
Endocrine therapies to alter the action/amount of oestrogen will have some effect on the cancer
Where is the oestrogen receptor expressed?
ONLY on luminal epithelial cells (but not all of them)
NOT myoepithelial cells
How is the oestrogen receptor involved in breast carcinoma?
Reversal of normal effect
Oestrogen responsive cells (myoepithelial cells and luminal epithelial cells w/o ER) directly respond to oestrogen as a GF and stimulate their own growth
- ER activation upon binding oestrogen
- Gene expression induced by binding to specific DNA sequences - oestrogen response elements
- Oestrogen-induced gene products increase cell proliferation, resulting in breast cancer
What is the normal oestrogen receptor response?
Response to oestrogen = stimulate growth
ER positive cells do not grow in response to oestrogen
They act as beacons to produce GFs that stimulate growth of nearby cells
What are the important risk factors for breast cancer?
Lifetime exposure to oestrogens:
- Early age of onset of menstruation
- Late age to menopause
- Age to first full-term pregnancy (older is worse)
- Some contraceptive pills
- Some HRTs
What role do endocrine therapies play in the treatment of breast cancer?
Major therapeutic value in ER-positive tumours
Some evidence of prevention (anti-oestrogens)
Adjuvant to remove micrometastases
Neoadjuvant to attempt to downstage tumour before surgery
Explain the pathophysiology of breast cancer
- Oestrogen and progesterone are important regulators of normal breast growth and development as well as breast involution and play important roles in pathogenesis of breast cancer
- A variety of factors, both genetic and environmental, may disrupt normal growth regulatory pathways resulting in the development of cancer: endogenous and exogenous hormone exposure, ionising radiation exposure, and genetic mutations in DNA repair genes are among the more well-known factors contributing to breast cancer development
- Cellular stimulation of ER can have negative consequences in patients expressing large numbers of ER intracellularly –> increased proliferation
- HER2 overexpressed
- All lesions arise from TERMINAL duct lobular units
What are the endocrine therapies used in breast cancer treatment?
- Ovarian suppression - limit oestrogen production is premenopausal women - LHRH agonits
- Block oestrogen production by enzymatic inhibition - aromatase inhibitors (post-menopausal women)
- Inhibit oestrogen responses - competitive inhibitors of ER - anti-oestrogens, e.g. tamoxifen (selective ER modulator), faslodex
