Breast Cancer Flashcards
What are the pathologic types of breast cancer?
- Ductal carcinoma in situe (DCIS)
- Lobular carcinoma in situ (LCIS)
- Invasive ductal carcinoma
Endocrine Therapy
- Deplete estrogen or block its effects
- Cytostatic: Block progression through cell cycle
- Started AFTER chemotherapy is complete
Selective Estrogen Receptor Modulator (SERM)
- MOA: Competes w/ estradiol binding to estrogen receptors
- Tamoxifen and Toremifene
What are some adverse effects of SERMs?
- Hot flashes
- Vaginal discharge/dryness
- Irregular menses
- Endometrial thickness
What are some serious adverse effects of SERMs?
- Thromboembolism
- Endometrial/uterine cancer
Tamoxifen
Significant drug interactions with CYP2D6 inhibitors
* ex: fluoxetine, paroxetine, and bupropion
* May prevent bone loss
* May lower total cholesterol
Aromatase inhibitors
- Inhibit armotase
- Should NOT be used as single agent therapy for premenopausal women
- Exemestine, Anastrozole, Letrozole
Exemestine
- Steroid (Type I)
- Irreversibly and covalently inactivates the enzyme
Anastrozole, Letrozole
- Non-steroidal (Type II)
- Reversibly binds to the enzyme
What are the adverse effects of aromatase inhibitors?
- Hot flashes
- Arthralgias/myalgias
- Bone loss with long-term use
- Vaginal dryness
- Headaches
- Diarrhea
- Mild nausea
- Alopecia and hair thinning
What is the choice of endocrine therapy for premenopausal?
- Tamoxifen for 5-10 years
OR - Ovarian suppression or ablation PLUS either: Tamoxifen or AI
What is the choice of endocrine therapy for postmenopausal?
- 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)
What are the common adjuvant chemotherapy regimens for HER- negative breast cancer?
- AC followed by paclitaxel
- AC = doxorubicin + cyclophosphamide
- TC (docetaxel + cyclophosphamide)
What are the targeted therapy options for early stage HR + HER2- treatment?
- Olaparib (PARP inhibitor)
- Abemaciclib (CDK4/6 inhibitor)
Trastuzumab (Herceptin)
- Use in all settings
- Major adverse effects: Cardiac
- Do NOT administer with an anthracycline
Pertuzumab (Perjeta)
- Use in all settings
- Use in combination with trastuzumab
- Major adverse effect: cardiac
- Do NOT give with an anthracycline
Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf (Phesgo)
- Use in all settings
- Administer SQ
Neratinib (Nerlynx)
- Use as extended adjuvant therapy and metastatic disease
- Administer orally
What is the MOA of Neratinib?
Blocks ATP binding site on intracellular domain of HER2 molecule
What are the toxicities of Neratinib and how do you prevent it?
- Diarrhea, N/V, abdominal pain, rash, stomatitis, AST/ALT increase
- Recommend prophylactic scheduled loperamide for 1st 8 weeks of treatment
Ado-trastuzumab emtansine
- Use in as adjuvant therapy (for residual disease) and for metastatic cancer
Fam-trastuzumab deruxtecan-nxki (Enhertu)
- Use in metastatic cancer
Lapatinib (Tykerb)
- Use in metastatic cancer
- Administer orally
Tucatinib
- Use in metastatic cancer
- Administer orally
Margetuximab
- Use in metastatic cancer
What are some common adjuvant chemotherapy regimen for HER2 targeted therapy?
- AC to taxane + concurrent trastuzumab +/- pertuzumab
- TCH (docetaxel, carboplatin, and trastuzumab) +/- pertuzumab
- Paclitaxel + trastuzumab (consider patient w/ low risk)
What is the targeted therapy for HR- HER- treatment?
- Olaparib (PARP inhibitor)
What is the immunotherapy for HR- HER- treatment?
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
What is the 1st line treatment for HR+ HER2- Metastatic Breast Cancer of Endocrine targeted therapy?
- CDK4/6 inhibitor + AI
- CDK4/6 inhibitor + fulvestrant
Palbociclib
- CDK4/6 inhibitors for HR+ HER- metastatic cancer
- Causes neutropenia
Riboclicib
- CDK4/6 inhibitors for HR+ HER- metastatic cancer
- Causes neutropenia, hepatotoxicity, and QTc prolongation
Abemaciblib
- CDK4/6 inhibitors for HR+ HER- metastatic cancer
- Causes neutropenia, diarrhea, VTE, hepatotoxicity
Alpelisib
- 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
Capivasertib
- 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
Everolimus
- 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
