Breast Cancer Chemotherapy

Question 1

*Doxorubicin (Adriamycin)
*Epirubicin (Ellence)
Daunorubicin (Cefrubidine)
Idarubicin (Idamycin)
Mitoxantrone (Novantrone)

Answer 1

Breast Cancer Chemo
Anthracyclines
MOA
a. Inhibition of DNA topoisomerase II catalytic activity
b. Activation of signal transduction pathways
c. Generation of reactive oxygen intermediates
d. Stimulation of apoptosis
ADE
a. *Colored urine (Dox→pink-red/orange; Mit→green)
b. *Cardiac toxicity (dose limiting toxicity)
i. Acute – arrhythmias, pericarditis
ii. Chronic – CHF-like sx
c. Myelosuppression
d. Mucositis
e. Alopecia
f. Nausea/ vomiting
g. Tissue damage if extravasation occurs
Dosing
- dose reduction w/ hepatic dysfx

Question 2

Paclitaxel (Taxol)
Docetaxel (Taxotere)
Albumin-bound Paclitaxel (Abraxane)
Ixabepilone (Ixempra)
Cabazitaxel (Jevtana)

Answer 2

Breast Cancer Chemo
Taxanes
MOA
a. Low concentrations inhibit microtubule dynamics (dynamic instability and treadmilling)
b. High concentrations inhibit depolymerization of tubulin
i. Effect cell division at microtubules
c. Cell cycle specific to *mitosis phase
ADE
a. *Peripheral neuropathy (hands and feet)
b. Neutropenia (dose limiting toxicity)
c. Alopecia
d. Hypersensitivity reaction
e. Anemia/thrombocytopenia
f. Arthralgias
g. Skin and nail changes

Question 3

Tamoxifen

Answer 3

Breast Cancer Chemo
Selective Estrogen Receptor Modulators (SERM)
- *used for tx & prevention
MOA
a. Competitively binds to estrogen receptors on tumors and other tissue targets, producing a nuclear complex that decrease DNA synthesis and inhibits estrogen effects
b. Cytostatic (stops cell growth) rather than cytocidal (kills)
ADE
a. Hot flashes
b. Gynecologic effects 
c. Ophthalmologic (cataracts)
d. Thrombosis (PE)
e. Lipoprotein effects
f. Hepatic Toxicity
g. Bone effects (INC bone density in post-menopausal women)
C/I
a. Pregnancy
b. Male breast cancer (cause impotence and nocturnal priapism)
Drug Interactions
a. CYP3A4
b. CYP2D6/SSRIs
c. Aromatase Inhibitor (Letrozole)
d. Medroxyprogesterone
e. Warfarin

Question 4

Raloxifene

Answer 4

Breast Cancer Chemo
Selective Estrogen Receptor Modulators (SERM)
2. As effective in *prevention of breast cancer as tamoxifen
3. Not use early or advanced stage treatment
MOA
- Similar agonist/antagonist effects of tamoxifen except on endometrium
Drug Interactions
5. Fewer drug interactions

Question 5

Fulvestrant

Answer 5

Breast Cancer Chemo
Pure Antiestrogen (AKA Selective Estrogen Receptor Downregulator) (SERD)
- *Clinical used in tamoxifen resistance (SERMs)
Mechanism of Action
a. Similar to tamoxifen except it is a pure estrogen antagonist
ADE
a. Decreased bone mineral density
b. Hot flashes
c. GI disturbances
Pharmacology
a. IM depot due to lack of consistent oral absorption
b. Given as two 2.5 ml injections

Question 6

Aromatase Inhibitors

Answer 6

Breast Cancer Chemo
MOA
a. Inhibits aromatase (DEC estrogen)
ADE
a. Hot flashes
b. Myalgias
c. Arthritis (hands)
d. Arthralgias
e. Increased osteoporosis

Question 7

Trastuzumab

Answer 7

Breast Cancer Chemo
MOA
a. Prevent dimerization of HER2 with HER2 (human epidermal growth factor receptor 2)
ADE
a. Cardiac toxicity
b. Infusion related reactions (chills, rigor, pain, tachycardia, SOB)
c. Diarrhea

Question 8

Ado-Trastuzumab Emtansine

Answer 8

Breast Cancer Chemo
Indication
a. Metastatic breast cancer who have received trastuzumab and taxane previously
MOA
a. Antibody-Drug Conjugate (DM1 – a microtubule inhibitor)
b. Upon internalization of conjugate by HER2 positive cell, DM1 binds to tubulin and disrupts the microtubule networks ultimately leading to apoptosis
ADE
a. Nausea/Vomiting
b. Myelosuppression
c. Headaches
d. Peripheral Neuropathy
e. Cardiac toxicity
f. Infusion reactions

Question 9

Pertuzumab

Answer 9

Breast Cancer Chemo
Indications
a. Rapidly expanding
b. In combination with trastuzumab (to DEC resistance for trastuzamab)
c. Neoadjuvant, adjuvant, metastatic
MOA
a. Prevent dimerization of HER2 with HER3
ADE
a. Diarrhea
b. Rash/Itching
c. Mouth Sores
d. Infusion reaction
e. Cardiac toxicity

Question 10

Everolimus

Answer 10

Breast Cancer Chemo
Indication
a. In combination with exemestane in post-menopausal women with recurrent hormone receptor positive breast cancer after failure of either letrozole or anastrozole
MOA
a. mTOR pathway inhibitor
ADE
a. Stomatitis
b. Noninfectious Pneumonitis
c. Hyperglycemia
d. Hyperlipidemia