Breast Cancer

Question 1

Rx list

Answer 1

• SELECTIVE ESTROGEN REC MODULATORS (SERMs) : Tamoxifen, Toremifene
• ESTROGEN REC BLOCK: Fluvestrant
• GNRH AGs: Leuprolide
• AROMATASE INHIBITORS (AIs): Anastrozole, Exemestane
• BIOs: Trastuzumab, Pertuzumab

Question 2

Breast cancer subtypes

Answer 2

DETERMINES TX

• ESTR + (ER+) = MOST, will be PR+ (progest) = surgery/radiation+ tamoxifen (best ER+/PR+/HER2-) {BEST}
• HER2+ = surgery/radiation + trastuzumab +/-chemo
• TRIPLE (-)= BRCA-1, NO hormones, Surg/Radiation + chemo {WORST]

Question 3

Menopausal Timing

Answer 3

• SERMS= pre+post
• GNRH AG= Pre
• AROMATASE BLOCK= Post

Question 4

Tamoxifen

Answer 4

ER+ SERM

• PRODRUG= Needs cyp 2d6 (don’t genotype for now)
• Block ERa/b in breast
• S.E.= ag to stim clotting factors, up risk of endo cancer (not take past 5-10 years)
• Why kill breast tumor but not endometrial tumors= co-repressors / co-activators

Question 5

GNRH AGs

LEUPROLIDE / goserelin

Answer 5

• W/ SERMS, prostate cancer

* S.E.: hot flash, osteoporosis, sex dysfunction, C/I preg

Question 6

Aromatase Block

ANASTROZOLE, LETROZOLE, EXEMESTANE

Answer 6

• Adjuvant for 5y, then this 5 yr
• Stop coversion testoserone—>estrogen (aromatase)
• S.E.: hot flashes, osteopenia, osteoporosis

Question 7

HER2+ breast cancer

Answer 7

• DX: FISH mapping, >6 copies of HER2 gene; immunohistochemistry (brown stain)
• Ligand (EGF)-independent EGFR/HER2 dimerization
• TX: Trastuzumab

Question 8

Trastuzumab

Answer 8

• MOA: binds HER2 protein, stops dimerization, mitotic spindle poisons, sensitize to chemo, recruit immune cells
• S.E.: infusion rxn (N/V, pain) tx: acetamin/benadryl; CHF (stop Tx!); possible resistance in 1 yr (tx: Lapitinib)

METASTATIC? Trastuzumab + Pertuzumab + docetaxel

Question 9

Breast Cancer Prognosis (later metastisis)

Answer 9

*MammaPrint= all cancer types, 70genes, High-risk/low-risk 10-yr
*Oncotype DX= lymph neg/pos, ER+ HER2-, receiving tamoxifen;
0-100 score (lower score better), also show which will have better outcome with tamoxi+chemo combo (low=tamoxi only, high= tamoxi+chemo)