Breast Cancer

Question 1

What are the pathologic types of breast cancer?

Answer 1

• Ductal carcinoma in situe (DCIS)
• Lobular carcinoma in situ (LCIS)
• Invasive ductal carcinoma

Question 2

Endocrine Therapy

Answer 2

• Deplete estrogen or block its effects
• Cytostatic: Block progression through cell cycle
• Started AFTER chemotherapy is complete

Question 3

Selective Estrogen Receptor Modulator (SERM)

Answer 3

• MOA: Competes w/ estradiol binding to estrogen receptors
• Tamoxifen and Toremifene

Question 4

What are some adverse effects of SERMs?

Answer 4

• Hot flashes
• Vaginal discharge/dryness
• Irregular menses
• Endometrial thickness

Question 5

What are some serious adverse effects of SERMs?

Answer 5

• Thromboembolism
• Endometrial/uterine cancer

Question 6

Tamoxifen

Answer 6

Significant drug interactions with CYP2D6 inhibitors
* ex: fluoxetine, paroxetine, and bupropion
* May prevent bone loss
* May lower total cholesterol

Question 7

Aromatase inhibitors

Answer 7

• Inhibit armotase
• Should NOT be used as single agent therapy for premenopausal women
• Exemestine, Anastrozole, Letrozole

Question 8

Exemestine

Answer 8

• Steroid (Type I)
• Irreversibly and covalently inactivates the enzyme

Question 9

Anastrozole, Letrozole

Answer 9

• Non-steroidal (Type II)
• Reversibly binds to the enzyme

Question 10

What are the adverse effects of aromatase inhibitors?

Answer 10

• Hot flashes
• Arthralgias/myalgias
• Bone loss with long-term use
• Vaginal dryness
• Headaches
• Diarrhea
• Mild nausea
• Alopecia and hair thinning

Question 11

What is the choice of endocrine therapy for premenopausal?

Answer 11

• Tamoxifen for 5-10 years
  OR
• Ovarian suppression or ablation PLUS either: Tamoxifen or AI

Question 12

What is the choice of endocrine therapy for postmenopausal?

Answer 12

• AI for 5-10 years
• Other options:
  
  • Various schedules of AI to tamoxifen or tamoxifen to AI (continued for a total of 5-10 years)
  • Tamoxifen for 10 years (if contraindication to AI)

Question 13

What are the common adjuvant chemotherapy regimens for HER- negative breast cancer?

Answer 13

• AC followed by paclitaxel
  
  • AC = doxorubicin + cyclophosphamide
• TC (docetaxel + cyclophosphamide)

Question 14

What are the targeted therapy options for early stage HR + HER2- treatment?

Answer 14

• Olaparib (PARP inhibitor)
• Abemaciclib (CDK4/6 inhibitor)

Question 15

Trastuzumab (Herceptin)

Answer 15

• Use in all settings
• Major adverse effects: Cardiac
• Do NOT administer with an anthracycline

Question 16

Pertuzumab (Perjeta)

Answer 16

• Use in all settings
• Use in combination with trastuzumab
• Major adverse effect: cardiac
• Do NOT give with an anthracycline

Question 17

Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf (Phesgo)

Answer 17

• Use in all settings
• Administer SQ

Question 18

Neratinib (Nerlynx)

Answer 18

• Use as extended adjuvant therapy and metastatic disease
• Administer orally

Question 19

What is the MOA of Neratinib?

Answer 19

Blocks ATP binding site on intracellular domain of HER2 molecule

Question 20

What are the toxicities of Neratinib and how do you prevent it?

Answer 20

• Diarrhea, N/V, abdominal pain, rash, stomatitis, AST/ALT increase
• Recommend prophylactic scheduled loperamide for 1st 8 weeks of treatment

Question 21

Ado-trastuzumab emtansine

Answer 21

• Use in as adjuvant therapy (for residual disease) and for metastatic cancer

Question 22

Fam-trastuzumab deruxtecan-nxki (Enhertu)

Answer 22

• Use in metastatic cancer

Question 23

Lapatinib (Tykerb)

Answer 23

• Use in metastatic cancer
• Administer orally

Question 24

Tucatinib

Answer 24

• Use in metastatic cancer
• Administer orally

Question 25

Margetuximab

Answer 25

* Use in metastatic cancer

Question 26

What are some common adjuvant chemotherapy regimen for HER2 targeted therapy?

Answer 26

* AC to taxane + concurrent trastuzumab +/- pertuzumab * TCH (docetaxel, carboplatin, and trastuzumab) +/- pertuzumab * Paclitaxel + trastuzumab (consider patient w/ low risk)

Question 27

What is the targeted therapy for HR- HER- treatment?

Answer 27

* Olaparib (PARP inhibitor)

Question 28

What is the immunotherapy for HR- HER- treatment?

Answer 28

Pembrolizumab * Continued with chemotherapy before surgery and continued as single agent after surgery * Pembrolizumab + carboplatin + paclitaxel for 12 weeks to pembrolizumab + AC every 3 weeks for 4 cycles

Question 29

What is the 1st line treatment for HR+ HER2- Metastatic Breast Cancer of Endocrine targeted therapy?

Answer 29

* CDK4/6 inhibitor + AI * CDK4/6 inhibitor + fulvestrant

Question 30

Palbociclib

Answer 30

* CDK4/6 inhibitors for HR+ HER- metastatic cancer * Causes neutropenia

Question 31

Riboclicib

Answer 31

* CDK4/6 inhibitors for HR+ HER- metastatic cancer * Causes neutropenia, hepatotoxicity, and QTc prolongation

Question 32

Abemaciblib

Answer 32

* CDK4/6 inhibitors for HR+ HER- metastatic cancer * Causes neutropenia, diarrhea, VTE, hepatotoxicity

Question 33

Alpelisib

Answer 33

* PI3K pathway inhibitor * Indicated in combination w/ fulvestrant for patients with: - HR+, HER- - PI3CA-mutated metastatic breast cancer - Following progression on or after an endocrine-based regimen * Causes hyperglycemia

Question 34

Capivasertib

Answer 34

* PI3K/AKT/PTEN pathway inhibitor * Indicated in combination with fulvestrant for patients with: - HR+, HER2- - PIK3CA-, AKT1, and/or PTEN-mutated metastatic breast cancer - Following progression on or after an endocrine-based regimen * Following progression on or after an endocrine-based regimen * Causes hyperglycemia, rash

Question 35

Everolimus

Answer 35

* mTOR pathway inhibitor * Inhibited in combination with endocrine therapy for patients with: - HR+, HER2- - Following progression on or after an endocrine-based regimen * Causes stomatitis