B8.039 Prework 1: Breast Cancer Overview

Question 1

breast cancer epidemiology

Answer 1

most common cancer in women

second most common cause of cancer deaths in women (after lung)

Question 2

sporadic vs inherited breast cancer

Answer 2

90% sporadic (no family history)

10% is inherited

Question 3

unavoidable risk factors for breast cancer

Answer 3

gender
age (>55)
fam history (2x risk if mother or sister with BC)
genetics (BRCA1/2)
race
breast density

Question 4

lifestyle factors that contribute to breast cancer risk

Answer 4

obesity
high alcohol consumption
nulliparity
HRT

Question 5

estrogen lifetime exposure factors

Answer 5

age of menarche
age of menopause
exposure to environmental estrogens
HRT
oral contraceptives
obesity

Question 6

how is estrogen relevant to cancer

Answer 6

estradiol (and other steroid hormones) drive cell proliferation which facilitates fixation of genetic errors

Question 7

histologic subtypes of breast cancer

Answer 7

preinvasive cancer (25%)
invasive cancer (75%)
-extension beyond BM

Question 8

characterize DCIS

Answer 8

80% of preinvasive cancer
may spread through ducts and distort duct architecture
1% progresses to invasive cancer per year
usually unilateral

Question 9

characterize LCIS

Answer 9

20% of preinvasive cancer
does not distort duct architecture
e-cadherin loss
1% progresses to invasive cancer per year
can be bilateral

Question 10

characterize IDC

Answer 10

79% of invasive cancers
usually from DCIS precursor
cause fibrous response, producing a palpable mass on examination
mets through lymphatics and blood

Question 11

characterize ILC

Answer 11

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+

Question 12

molecular subtypes of BC

Answer 12

triple negative- 15-20%
HER2+ - 10-15%
luminal B - 20%
luminal A - 40%

Question 13

basal/ myoepithelial cells

Answer 13

contractile cells for milk ejection
estrogen receptor -
progesterone receptor -

Question 14

luminal/epithelial cells

Answer 14

respond to hormonal stimulation
ER +
PR +/-

Question 15

where do breast cancers arise from

Answer 15

TDLUs

Question 16

luminal A

Answer 16

ER+

PR+

Question 17

luminal B

Answer 17

ER+

PR+/-

Question 18

what % of breast cancer tumors are E dependent

Answer 18

75%

express estrogen receptors

Question 19

how do you test cells for ERs

Answer 19

IHC

Question 20

mechanism of estradiol on cell function

Answer 20

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

Question 21

hormonal therapy options for breast cancer

Answer 21

aromatase inhibitors
-anastrozole
-exemestane
-letrozole
antiestrogens
-tamoxifen
-fulvestrant

Question 22

antibody (targeted) therapy

Answer 22

trastuzumab

pertuzumab

Question 23

endocrine therapy sequence for premenopausal women ER+

Answer 23

tamoxifen +/- ablation of ovarian function
DO NOT use AIs, ovaries are still functioning
-could potentially use them w an ovary suppressing agent

Question 24

endocrine therapy sequence for postmenopausal women ER+

Answer 24

Tamoxifen > AIs
OR
AIs > Tamoxifen
OR either individualls

Question 25

use of fulvestrant

Answer 25

second line therapy for ER+ breast cancer if tamoxifen or AIs fail

Question 26

what is HER2 positivity

Answer 26

overexpression: marked increase in number of HER2 receptors on the cell surface
amplification: increase in number of HER2/neu gene copies in the nucleus

Question 27

difference between FISH and IHC

Answer 27

FISH looks at gene copies, IHC looks at protein expression
FISH for HER2
IHC for ER/PR