B8.039 Prework 1: Breast Cancer Overview Flashcards
breast cancer epidemiology
most common cancer in women
second most common cause of cancer deaths in women (after lung)
sporadic vs inherited breast cancer
90% sporadic (no family history)
10% is inherited
unavoidable risk factors for breast cancer
gender age (>55) fam history (2x risk if mother or sister with BC) genetics (BRCA1/2) race breast density
lifestyle factors that contribute to breast cancer risk
obesity
high alcohol consumption
nulliparity
HRT
estrogen lifetime exposure factors
age of menarche age of menopause exposure to environmental estrogens HRT oral contraceptives obesity
how is estrogen relevant to cancer
estradiol (and other steroid hormones) drive cell proliferation which facilitates fixation of genetic errors
histologic subtypes of breast cancer
preinvasive cancer (25%) invasive cancer (75%) -extension beyond BM
characterize DCIS
80% of preinvasive cancer
may spread through ducts and distort duct architecture
1% progresses to invasive cancer per year
usually unilateral
characterize LCIS
20% of preinvasive cancer does not distort duct architecture e-cadherin loss 1% progresses to invasive cancer per year can be bilateral
characterize IDC
79% of invasive cancers
usually from DCIS precursor
cause fibrous response, producing a palpable mass on examination
mets through lymphatics and blood
characterize ILC
10% of invasive cancers
usually from LCIS precursor
minimal fibrous response, presents less often with palpable mass
mets through abdominal viscera to GI, ovaries, uterus
almost always ER+
molecular subtypes of BC
triple negative- 15-20%
HER2+ - 10-15%
luminal B - 20%
luminal A - 40%
basal/ myoepithelial cells
contractile cells for milk ejection
estrogen receptor -
progesterone receptor -
luminal/epithelial cells
respond to hormonal stimulation
ER +
PR +/-
where do breast cancers arise from
TDLUs
luminal A
ER+
PR+
luminal B
ER+
PR+/-
what % of breast cancer tumors are E dependent
75%
express estrogen receptors
how do you test cells for ERs
IHC
mechanism of estradiol on cell function
E binds to ER in membrane
ER translocated into cell and dimerizes
ER dimer translocates into nucleus to increase transcription of estrogen responsive genes; increased cell proliferation
hormonal therapy options for breast cancer
aromatase inhibitors -anastrozole -exemestane -letrozole antiestrogens -tamoxifen -fulvestrant
antibody (targeted) therapy
trastuzumab
pertuzumab
endocrine therapy sequence for premenopausal women ER+
tamoxifen +/- ablation of ovarian function
DO NOT use AIs, ovaries are still functioning
-could potentially use them w an ovary suppressing agent
endocrine therapy sequence for postmenopausal women ER+
Tamoxifen > AIs
OR
AIs > Tamoxifen
OR either individualls
use of fulvestrant
second line therapy for ER+ breast cancer if tamoxifen or AIs fail
what is HER2 positivity
overexpression: marked increase in number of HER2 receptors on the cell surface
amplification: increase in number of HER2/neu gene copies in the nucleus
difference between FISH and IHC
FISH looks at gene copies, IHC looks at protein expression
FISH for HER2
IHC for ER/PR
