Breast and Endometrial Cancer Drugs

Question 1

Aromatase inhibitors

Answer 1

anastrozole, exemestane, letrozole

Question 2

SERMs

Answer 2

raloxifene, tamoxifen, toremifene

Question 3

SERD

Answer 3

fulvestrant

Question 4

GnRH agonist

Answer 4

goserelin

Question 5

HER2 blockers

Answer 5

pertuzumab, trastuzumab, ado-trastuzumab emtasine

Question 6

TKI

Answer 6

lapatinib

Question 7

mTOR inhibitor

Answer 7

everolimus

Question 8

What does BRCA enzyme do?

Answer 8

DNA damage repair during G2 and S phases

mutation causes division of cells w/ damaged DNA

Question 9

What is the best tx for BRCA carriers?

Answer 9

prophylactic bilat mastectomy and salpingo-oophorectomy

Question 10

how effective are SERMs in BRCA cases?

Answer 10

hardly at all for BRCA1

more effective for BRCA2

Question 11

interventions for premenopausal women

Answer 11

surgical ablation of ovaries
GnRH agonists
SERMs

Question 12

interventions for postmenopausal women

Answer 12

aromatase inhibitors

SERMS/SERDs

Question 13

MOA of estrogen receptor

Answer 13

estrogen binds –> dimerization of receptor –> complex translocated to nucleus –> binds to DNA binding site –> associates w/ ERE and other cofactors

Question 14

MOA of HER2/neu receptor

Answer 14

growth factor ligands bind –> dimerization of receptor –> activation of MAP kinase pathway

Question 15

MOA of fulvestrant

Answer 15

estrogen antagonist –> downregulation of receptors

used in postmenopausal women

Question 16

side effects of fulvestrant

Answer 16

menopause sx

Question 17

MOA SERMs

Answer 17

selective tissue estrogen agonist or antagonist (depends on what tissue)

Question 18

adverse effects of SERMs

Answer 18

endometrial hyperplasia, VTE/stroke, vaginal bleeding, endometrial cancer, retinal degeneration, teratogen
prolonged QT (toremifene)

Question 19

significance of CYP metabolism w/ SERMs

Answer 19

tamoxifen metabolized by CYP2D6 to more potent metabolites
poor metabolizers (w/ CYP2D6 variations) won't get full clinical effect of drug

Question 20

aromatase inhibitors MOA

Answer 20

block CYP19A1 activity –> blocking of aromatase activity

Question 21

adverse effects of aromatase inhibitors

Answer 21

arthralgia, diarrhea
teratogenic
menopause sx

Question 22

how is aromatase inhibitor best used?

Answer 22

after SERM therapy or swapping w/ SERM during treatment period

Question 23

pertuzumab MOA

Answer 23

blocks dimerization of HER2 receptor

Question 24

pertuzumab adverse effects

Answer 24

leukopenia

BBW for pregnancy

Question 25

trastuzumab MOA

Answer 25

binds to juxtaglomerular region of HER2 receptor

Question 26

trastuzumab adverse effects

Answer 26

cardiomyopathy, heart failure, renal failure, hepatotoxic, respiratory failure BBW for cardiomyopathy, respiratory distress/insufficiency, pregnancy

Question 27

ado-trastuzumab emtasine (TDM1) MOA

Answer 27

trastuzumab linked to TDM1 --> taken into cell and broken apart in lysosome --> trastuzumab binds to receptor normally, TDM1 inhibits microtubule activity within cell

Question 28

ado-trastuzumab emtasine (TDM1) adverse effects

Answer 28

BBW for heart failure, hepatic dz, ventricular dysfunction, pregnancy

Question 29

lapitinib MOA

Answer 29

binds to intracellular ATP binding site on HER2 --> prevents activation

Question 30

metabolism of lapatinib

Answer 30

hepatic via CYP3A4

Question 31

lapatinib adverse effects

Answer 31

QT prolongation, interstitial lung dz

Question 32

goserelin MOA

Answer 32

GnRH agonist --> provides continuous supply of GnRH rather than pulsatile --> downregulation of receptors

Question 33

goserelin adverse effects

Answer 33

initial flare of dz --> bone pain from mets, hypercalcemia | eventually osteopenia, other menopause sx

Question 34

everolimus MOA

Answer 34

inhibits mTOR activity

Question 35

everolimus adverse effects

Answer 35

increased risk of infection, non-infectious pneumonitis

Question 36

conventional chemo adverse effects

Answer 36

doxorubicin -- cardiotoxicity cyclophosphamide -- hemorrhagic cystitis taxanes -- peripheral neuropathy

Question 37

medroxyprogesterone MOA

Answer 37

progestin analog --> inhibits GnRH release

Question 38

megestrol MOA

Answer 38

progestin analog --> LH inhibition, differentiation/maintenance of endometrium

Question 39

endometrial cancer drugs

Answer 39

medroxyprogesterone, megestrol