Breast Cancer: Anti-Estrogen treatment

Question 1

What is the typical responsiveness of anti-estrogen treatment in Estrogen sensitive tumors?

Answer 1

The tumors are typically responsive to treatment within 8-12 weeks. The average remission lasts 6-12 months

Question 2

What drug is a Selective Estrogen Receptor Downregulator?

Answer 2

Fulvestrant

Question 3

What is the MOA of Fulvestrant?

Answer 3

Fulvestrant is a pure antagonist of Estrogen. It binds to the ER and prevents dimerization which in turn prevent nuclear localization and increases degradation.

Question 4

What is the ADME of Fulvestrant?

Answer 4

Monthly IM injections

Hepatic metabolism

Question 5

What adverse effects are associated with fulvestrant?

Answer 5

Essentially symptoms of menopause:
nausea
asthenia
vasodilation (hot flash)
Headache

Question 6

What Drugs belong to the SERM group?

Answer 6

Tamoxifen
Raloxifen
Toremifene

Question 7

What is the MOA of the SERMs?

Answer 7

Location dependent agonistic/antagonistic effects on estrogen receptors.

Question 8

What is the effect of SERMs on bone?

Answer 8

SERMs have an agonistic effect on bone. Thus they increase bone density.

Question 9

What effect do SERMs have on breast and other tissues?

Answer 9

They are antagonistic in breast tissue thus inhibiting tumor growth. In other tissues they increase apoA1 and decrease LDL, cholesterol, and lipoproteins.

Question 10

What are some common and serious adverse effects of SERMs?

Answer 10

Teratogenic
Retinal degeneration
DVT/PE/stroke

Question 11

What is the ADME of tamoxifen?

Answer 11

Daily PO,

metabolized by CYP2D6

Question 12

What are some effects unique to tamoxifen?

Answer 12

Can cause endometrial hypertrophy
Vaginal bleeding
Endometrial cancer

Question 13

What is the ATLAS study?

Answer 13

The ATLAS study showed that the benefit of 10yr adjuvant therapy with tamoxifen outweighed the potential risk of endometrial cancer.

Question 14

What is the ADME of Raloxifene?

Answer 14

Monthly IM injections

No agonism in the Endometrium.

Question 15

What is the ADME of Toremifene?

Answer 15

Derivative of tamoxifen
Daily PO
CYP3A4

Question 16

What adverse effects are unique to Toremifene?

Answer 16

Prolongation of QT interval

Agonizes ER in endometrium

Question 17

What drugs belong to aromatase inhibitor class?

Answer 17

Anastrozole
Letrozole
Exemestane

Question 18

When are the aromatase inhibitors used?

Answer 18

They are used for all ER+ post menopausal breast cancers.

Question 19

Which aromatase inhibitor is steroid derived?

Answer 19

Exemestane

Question 20

What is the MOA of aromatase inhibitors?

Answer 20

They prevent the conversion of testosterone to estrogen by aromatase (CYP19A1)

Question 21

What is the difference in MOA between steroidal and non-steroidal aromatase inhibitors?

Answer 21

The non-steroidal drugs are initiate reversible inhibition. The steroidal drug initiates irreversible inhibition.

Question 22

What is the ADME of the aromatase inhibitors?

Answer 22

daily PO

Hepatic metabolism

Question 23

What are the adverse effects of the aromatase inhibitors?

Answer 23

Hot flashes, Nausea
Hair thinning
Arthralgia
diarrhea

Question 24

How is HER2/neu testing done?

Answer 24

Immunohistochemistry

In situ hybridization

Question 25

Why is testing for HER2/neu important?

Answer 25

Because there are effective targeted therapies for HER2/neu tumors.

Question 26

What are the drugs used for HER2/neu therapy?

Answer 26

Trastuzumab Pertuzumab Lapatinib

Question 27

What is the MOA of trastuzumab?

Answer 27

Trastuzumab is a monclonal antibody against the HER2 extracellular domain

Question 28

What is the ADME of trastuzumab?

Answer 28

IV every 3 weeks

Question 29

What are some common adverse effects associated with trastuzumab?

Answer 29

``` GI upset Asthenia Blood dyscrasias Edema Rash Weight gain URTIs Dizziness ```

Question 30

What are the BBWs for trastuzumab?

Answer 30

``` Cardiomyopathy Infusion rxn Pregnancy ARDS/respiratory insufficiency Hepatotoxicity ```

Question 31

What is Ado-trastuzumab emtansine?

Answer 31

A small cytotoxic drug that is linked to trastuzumab. Trastuzumab binds and through endocytosis delivers the cytotoxic drug.

Question 32

What are the unique BBWs for Ado-Trastuzumab?

Answer 32

HF Liver disease Pregnancy Ventricular dysfunction

Question 33

What is the MOA of Pertuzumab?

Answer 33

mAb for HER2 dimerization domain.

Question 34

What is the ADME for Pertuzumab?

Answer 34

IV every 3 weeks

Question 35

What adverse effects are associated with Pertuzumab?

Answer 35

Hypersensitivity rxn Common: GI upset/asthenia/blood dyscrasias/fatigue/alopecia/loss of appetite Rare: Leukopenia, decreased LVEF

Question 36

What BBW is associated with Pertuzumab?

Answer 36

Pregnancy

Question 37

What is the MOA for lapatinib?

Answer 37

Lapatinib is a tyrosine kinase inhibitor for HER1 and HER2. It competes for ATP binding site to prevent down stream signaling.

Question 38

What is the metabolism of Lapatinib?

Answer 38

CYP 3A4 and 3A5 metabolism

Question 39

What BBW is associated with Lapatinib?

Answer 39

Liver disease

Question 40

What adverse effects are associated with Lapatinib?

Answer 40

Common: GI, blood dyscrasias, rash, headache, Backache, Hand-Foot syndrome Serious: Interstitial lung disease / pneumonitis, QT prolongation.