Breast & Endometrial Cancer

Question 1

MOA of Aromatase Inhibitors

Answer 1

Aromatase; Blocks production of estrone & estradiol

Question 2

Aromatase Inhibitors (3)

Answer 2

Anastrozole, Exemestane, Letrozole

Question 3

Aromatase Inhibitor Tox

Answer 3

Hot flashes; nausea; hair thinning; NO effect on adrenal steroids, thyroid, or other hormones; More arthralgia & diarrhea than tamoxifen but fewer gynecologic symptoms

Question 4

Aromatase Inhibitors Metabolism

Answer 4

Hepatic

Question 5

SERMs (3)

Answer 5

Raloxifene, Tamoxifen, Toremifene

Question 6

Raloxifene MOA

Answer 6

SERM; ER agonist/antagonist-estrogen effect on bone & anti-estrogen effect on mammary tissue

Question 7

Tamoxifen MOA

Answer 7

SERM; ER agonist/antagonist-estrogen effect on bone & anti-estrogen effect on mammary tissue

Question 8

Toremifene MOA

Answer 8

SERM; Tamoxifen derivative w/ anti-estrogenic properties

Question 9

Raloxifene Tox & BBW

Answer 9

Increased bone mineral density; Decreases serum cholesterol, LDL, & lipoproteins; Increases apolipoprotein-A1; Retinal degeneration at high doses

BBW= Thromboembolic Dz (DVT/PE) & Stroke

Question 10

Raloxifene Admin

Answer 10

Monthly IM

Question 11

SERMs & Pregnancy?

Answer 11

No, teratogens

Question 12

Tamoxifen Tox & BBW

Answer 12

Increased bone mineral density; Decreases serum cholesterol, LDL, & lipoproteins; Increases apolipoprotein-A1; Retinal degeneration at high doses

BBW= Endometrial Hypertrophy, vaginal bleeding, endometrial cancer, thromboembolic dz (DVT/PE), stroke

Question 13

Tamoxifen Admin

Answer 13

Daily PO

Question 14

Toremifene Tox & BBW

Answer 14

Similar AE’s to tamoxifen; Avoid w/ Hx of endometrial cancer/hyperplasia & thromboembolic dz

BBW= QT Prolongation (avoid in pre-existing conditions);

Question 15

Toremifene Admin

Answer 15

Daily PO

Question 16

Toremifene DDI

Answer 16

Avoid w/ CYP3A4 inhibitors

Question 17

SERD (1)

Answer 17

Fulvestrant

Question 18

Fulvestrant MOA

Answer 18

SERD; Pure antagonist, no estrogenic effects; Bulky substituent prevents dimerization of ER’s in nucleus=sustained downregulation of ER expression

Question 19

Fulvestrant Tox

Answer 19

Postmenopausal symptoms: nausea, asthenia, pain, vasodilation (hot flashes), and h/a

Question 20

Fulvestrnat PK

Answer 20

Hepatic metabolism; monthly IM-sustained plasma levels

Question 21

Fulvestrnat use

Answer 21

Tx for ER+ metastatic BC in PM women w/ dz progression following anti-estrogen therapy

Question 22

Trastuzumab MOA

Answer 22

HER2/neu Antibody; Binds to the juxtaglomerular region of the extracellular domain of HER2

Question 23

Trastuzumab Tox

Answer 23

Caution- HSR w/ initial dose; Common=GI upset, asthenia, blood dyscrasias, fatigue, peripheral edema, rash, wt gain, dizziness, URTIs, pharyngitis; Rare= cardiomyopathy & HF, renal failure, hepatotox, pneumonia, respiratory failure; BBWs

Question 24

Trastuzumab BBW

Answer 24

BBWs=Cardiomyopathy, Infusion Rxns, Pregnancy, Respiratory Distress Syndrome, Respiratory Insufficiency

Question 25

Lapatinib MOA

Answer 25

TKI

Question 26

Lapatinib Tox

Answer 26

Common= GI tox, anemia, thrombocytopenia, hand-foot syndrome, rash pain, h/a, backache; Serious= interstitial lung dz/pneumonitis, QT prolongation

Question 27

Lapatinib PK

Answer 27

Extensive hepatic metabolism- 3A4 + 3A5

Question 28

Lapatinib DDI

Answer 28

CI'd w/ concurrent use of drugs that have AE's associated w/ pulmonary tox & QT prolongation

Question 29

Lapatinib BBW

Answer 29

BBW=Liver Dz (b/c will lead to increased drug levels)- LFT monitoring required

Question 30

Everolimus MOA

Answer 30

mTOR Inhibitor; Prevents cell proliferation & survival

Question 31

Everolimus Tox & BBW

Answer 31

Non-infectious pneumonitis (sometimes fatal); Blood dyscrasias, hyperglycemia, hyperlipidemia, hypertriglyceridemia, elev creatinine, elev liver enzymes; N/V, diarrhea, pain, constipation Also BBW - opportunistic infections & neoplasia

Question 32

Everolimus PK

Answer 32

3A4 & Pgp substrate; Inhibits 3A4, 2D6, & Pgp

Question 33

What should you monitor when a patient is on everolimus

Answer 33

Monitor: blood glucose, CBC w/ differential, LFTs, serum bilirubin-creatinine-lipid profile- phosphate-triglyceride

Question 34

Everolimus use

Answer 34

Tx in combo w/ Exemestane for advanced ER+/HER2- tumors

Question 35

Which AI is steroidal, which non-steroidal?

Answer 35

Steroidal - exemestane | non-steroidal - letrozole, anastrazole

Question 36

Non steroidal AI is reversible or irreversible?

Answer 36

reversible inhibitor

Question 37

Steroidal AI is reversible or irreversible?

Answer 37

irreversible

Question 38

Which drugs are given in combo with a taxane?

Answer 38

Pertuzumab & Trastuzumab