Breast Cancer

Question 1

Risk factors for breast cancer

Answer 1

• female
• exposure to estrogen (including nulliparity, > 55 yo, HRT)
• BRCA1 or BRC2
• family history
• prior chest irradiation

get mammogram at 40 - 50 yo

Question 2

Stages of breast cancer

Answer 2

Stage 0: carcinoma in situ (DCIS)

Stage 1: small tumor, no lymph nodes

Stage 2: regional lymph nodes involved

Stage 3: lots of nodes

metastativ (IV): distant organs

Question 3

Hormone Receptor (HR) + Treatment

Answer 3

Estrogen and Progesterone Receptor

Positive response to endocrine therapy

• reduced risk of recurrence
• decreased mortality

Duration:
minimum 5, max 10 years

slower treatment onset than chemo

Question 4

Human Epidermal Growth Factor (HER2) + Treatment

Answer 4

Poor prognosis
Aggressive tumors

use HER2 targeting agents to decrease risk of disease recurrence

Recommended for metastatic: pertuzumab + trastuzumab + taxane

Question 5

Neoadjuvant Therapy

Answer 5

systemic treatment prior to locoregional therapy

indicated to reduce tumor size/burden prior to surgery

Question 6

Adjuvant Therapy

Answer 6

post-operative

used to eradicate all traces of tumor

Question 7

Tamoxifen

Answer 7

Hormone TX

Can be used for all menopausal stages; SERM
(antag in breast and vagina, ag in bone and uterus)

• *AEs**
• hot flashes and night sweats
• thromboembolic events
• endometrial hyperplasia
• • DDIS **
• CYP2D6 substrate, avoid with fluoxetine and paroxetine

Question 8

Hormonal Therapy: Pre menopause

Answer 8

Tamoxifen +/- ovarian suppression (ovarian ablation)

aromatase inhibitor + ovarian suppression

Question 9

Hormonal Therapy: Post-menopause

Answer 9

Tamoxifen

Aromatase inhibitors

Question 10

Hormonal Therapy: Peri-menopause

Answer 10

Aromatase inhibitors
tamoxifen

consider switching when status changes

Question 11

Pertuzumab

Answer 11

HER2 targeting; binds extracellular domain to prevent intracellular activation

• • AEs **
• Infusion reactions
• cardiotoxicity

** Monitoring **
LVEF

• *Notes **
• if patient has had previous infusion reaction, pre-med them for next time
• always given with trastuzumab
• do not give concurrently with anthracyclines unless you want to kill their heart

Question 12

Trastuzumab (Herceptin)

Answer 12

HER2 targeting; binds extracellular portion to prevent intracellular activation

• • AEs **
• infusion rxn
• cardiomyopathy (arrhythmias, reduced ejection fraction)
• *Monitoring **
• LVEF

Question 13

Anastrazole, Letrozole, Exemestane

Answer 13

aromatase inhibitors: inhibit peripheral conversion of androgens to estrogen

• • AEs **
• hot flashes and night sweats
• Osteoporosis & bone fractures
• GI upset
• • DDIs **
• Exemestane is a CYP3A4 substrate (increase dose with inducers)
• take exemestane after food to increase AUC

Question 14

Fulvestrant

Answer 14

Estrogen Receptor Antagonist

• • AEs **
• hot flashes
• • Notes**
• used in the setting of progressive dx, post aromatase inhib

Question 15

Leuprolide and Goserelin

Answer 15

LHRH Agonists

to cause ovarian ablation

• • AEs **
• hot flashes
• mood swings
• headache
• injection site pain
• • Notes **
• administered monthly to suppress estrogen levels

Question 16

Doxorubicin (Adriamycin)

Answer 16

DNA intercalator, topoisomerase inhibitor

• • AEs **
• N/V
• Extravasation (vesicant)
• irreversible cardiotoxicity
• myelosuppression
• Red discoloration of bodily fluids
• alopecia
• • Monitoring Parameters **
• LVEF at baseline
• LFTs (adjust)
• ANC/platelets
• EKG if suspected heart problems
• for fluid overload (HF)
• monitor cumulative dose
• • Notes **
• used in dose dense (ddAC) regimen = high emetogenicity)
• may require G-CSF prophylactically
• central line recommended (cold compress)

Question 17

Cyclophosphamide

Answer 17

DNA alkylator, metabolized to an acrolein

• • AEs **
• N/V
• hemorrhagic cystitis
• myelosuppression
• • Monitoring Parameters **
• SCr (adjust)
• LFTs (adjust)
• ANC/platelets
• • Notes **
• Requires hydration 1 -2 days after

Question 18

Paclitaxel (Taxol)

Answer 18

taxane: microtubule stabilizer (too stable!!)

• • AEs **
• Hypersensitivity (from cremophor)
• peripheral neuropathy
• alopecia
• myelosuppression
• • Monitoring Parameters **
• LFTs (adjust)
• ANC/platelets
• • Administration **
• premed with diphenhydramine, famotidine and dex to prevent cremophor reaction

Question 19

Docetaxel (Taxotere)

Answer 19

taxane: microtubule stabilizer

• • AEs **
• Hypersensitivity (not as severe as paclitaxel)
• Fluid retention
• • Monitoring Parameters **
• LFTs (dose adjust)
• ANC/platelets
• • Administration **
• premed with dex to prevent fluid retention

Question 20

Palbociclib

Answer 20

selective CDK 4/6 inhibitor

used in combo with letrozole

for HR/ER-positive but HER2 negative breast cancer

Question 21

Dexrazoxane

Answer 21

anthracycline antidote (chelates)

• helps with extravasation
• cardioprotective for high dose anthracyclines

Question 22

Ado-trastuzumab

Answer 22

targeted cytotoxin (maytansine) delivery. it’s a microtubule inhibitor

• • AEs**
• infusion reaction (fever, chills, dyspnea)
• cardiotox
• hepatotox
• abdominal pain
• diarrhea
• peripheral neurop
• thrombocytopenia
• • Monitoring**
• LVEF
• LFTs
• ANC/platelets
• • Notes **
• do not substitute for trastuzumab

Question 23

Lapatinib

Answer 23

binds tyrosine kinase to stop HER2 signaling

• • AEs **
• diarrhea (within 6 days)
• palmar-plantar erythrodyesthesia
• hepatotox
• cardiotox
• • Monitoring **
• LVEF
• QTc
• electrolytes
• LFTs (adjust)
• • Admin **
• take on empty stomach (because food increases AUC)
• • DDIs **
• CYP3A4 substrate

Question 24

MILD hypercalcemia of malignancy

Answer 24

Corrected calcium < 12 mg/dL

• • Treat **
• hydration PO
• the cancer

Question 25

Risk for hypercalcemia

Answer 25

breast cancer lymphoma multiple myeloma renal cell

Question 26

MODERATE hypercalcemia of malignancy

Answer 26

Corrected Calcium: 12 - 14 mg/dL may be asymptomatic * *Treatment** - Hydration IV - bisphosphonate IV - calcitonin (maybe) - treat the cancer

Question 27

SEVERE hypercalcemia of malignancy

Answer 27

Corrected Calcium > 14 mg/dL * * Treatment ** - Hydration IV - bisphosphonate IV - calcitonin - +/- dialysis - treat the cancer Sx: - malaise/fatigue, lethargy - confusion, coma - N/V - costipation - shortened QTc interval - renal impairment

Question 28

Corrected calcium

Answer 28

= measured serum calcium + 0.8 * (4 - albumin)

Question 29

Calcitonin

Answer 29

** Indication ** Hypercalcemia of malignancy,; maybe moderate, definitely severe ** MOA ** Inhibition of bone resorption Increased renal Ca excretion * * AEs ** - hypersensitivity - nausea ** Onset ** within 4 - 6 hours * * Notes ** - do not use as monotherapy, as it will cause tachyphylaxis w/in 2 days

Question 30

Bisphosphonates

Answer 30

** Preferred Agents ** Zoledronic Acid Pamidronate ** Indication ** Hypercalcemia of malignancy; moderate and severe ** MOA ** Inhibits osteoclast bone resorption * *AEs** - nephrotox - infusion reaction - osteonecrosis (jaw!!) * * Onset ** - 2 - 4 days - peak at 5 - 7 days * * Notes ** - can be given concurrently with fluids and calcitonin - C/I in severe renal dx, use denosumab instead

Question 31

Normal Saline for hypercalcemia of malignancy

Answer 31

* * MOA ** - want to increase calcium removal * *AEs** - fluid overload * * Onset ** - right then * * Notes ** - caution in CHF - caution if oliguric

Question 32

Denosumab

Answer 32

* Indication ** Refractory Hypercalcemia of malignancy: failed bisphosphonates ** MOA ** RANK-L mAb * *AEs** - bone pain - arthralgia - osteonecrosis) * * Onset ** - 3 days - peak: 9 days * * Notes ** - okay in chronic kidney dx (over bisphosphonates)

Question 33

Hemodialysis for hypercalcemia

Answer 33

* * indications ** - oliguric renal failure - hydration is unsafe - severe sx refractory to tx