Breast Cancer

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Author:
capnhue
ID:
149400
Filename:
Breast Cancer
Updated:
2012-04-29 00:43:22
Tags:
Regis University
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Description:
Breast Cancer
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  1. Risk Factors Breast Cancer
    • Female Gender: 1
    • Age >50: 1
    • Genetics: 4
    • family history of breast cancer at early age <50 (first degree relative)
    • two or more first degree relatives w/breast cancer
    • benign proliferative breast disease (LCIS)
    • hereditary genetic mutations (BRCA1, BRCA2, TP53)
    • Estrogen exposure: 5
    • prolonged HRT use
    • obesity
    • older age (>30) at first childbirth
    • nulliparity (have not given birth)
    • early menarche (>12), late menopause (>55)
    • Environmental: 2
    • previous exposure to therapeutic chest wall irradiation
    • alcohol use
  2. Gail Model
    • age
    • age at first menarche
    • age at first live birth or nulliparity
    • race/ethnicity
    • family history of breast cancer
    • number of past breast biopsies
    • number of breast biopsies that showed atypical hyperplasia
  3. Menstrual Cycyle changes
    • Menses (1-5): minimal edema, no mitoses/apoptosis, intraluminal secretions occurs
    • Follicular phase (next 2 wks): lobular acini develop double-cell layer appearance
    • Midluteal phase (3rd wk): stroma swelling occurs
    • Late luteal phase : extensive vacuolation (collection of waste) and increased inflammation, breast pain
  4. Screening Process for Breast Cancer
    • Mammogram: age 50-7, every 2 years (per USPTF)
    • First degree relative: 5yrs prior to age relative obtained breast cancer
    • BRCA mutation carrier: 10yrs prior to youngest relative
  5. Anthracycline MOA
    • Intercalation of DNA: interferes w/ DNA replication
    • Inhibition of topoisomerase II (Topo posions): once intercalated into DNA, topo posions prevent re-ligation of DNA during the repair process, leading to apoptosis
  6. Anthracycline Toxicity
    • acute: arrhythmias
    • chronic: heart failure
    • *treat w/ dexrazoxane
    • myelosuppression (dose-limiting)
    • mucositis
    • emesis
    • diarrhea
    • alopecia
  7. Anthracycline Lifetime dose limits
    • doxorubicin: 550mg/m2
    • daunorubicin: 1000mg/m2
    • epirubicin: 900 mg/m2
    • *doxorubicin @300mg/m2 treat w/ dexrazoxane
  8. Anthracycline IV extravasates treatment
    • dimethyl sulfoxide
    • dexrazoxane (totect)
  9. Vinorelbine adverse effects
    • alopecia
    • GI (constipation, diarrhea, emesis)
    • injection site reactions
    • leukopenia (dose-limiting)
    • peripheral neuropathy
  10. Trastuzumab MOA
    • inhibition of HER2 homo- or heterodimerization blocking tyrosine kinase activity, inhibiting cell growth
    • inhibition of HER2 angiogenesis
    • marking cancer cell so immune system can attack that cell
  11. Trastuzumab adverse effects
    • cardiotoxicity: heart failure
    • infusion related toxicity: ferver, chills, nausea, rash, dyspnea
    • *pretreatment w/ APAP & diphenhydramine (for infusion related toxicity)
  12. Lapatinib adverse effects
    • hand-foot syndrome
    • rash
    • diarrhea
    • fatigue
    • elevated LFTs
    • heart failure
    • black box warning: impaired liver funtion
  13. Tamoxifen drug-drug interactions
    • fluoxetine
    • bupropion
    • paroxetine
    • substitutes: citalopram, venlafaxine, excitalopram
  14. Tamoxifen adverse effects
    • hot flashes
    • irregular menses
    • vaginal bleeding
    • uterine malignancies
    • stroke
    • pulmonary embolism
    • category X
  15. Fulvestrant adverse effects
    • hot flashes
    • headache
    • nausea
    • injection site pain
    • category D
  16. Selective Estrogen Receptor Modulators (SERM)
    • Tamoxifen
    • Toremifene
  17. Selective Estrogen Receptor Downregulators (SERD)
    Fluvestrant
  18. Drugs targeting HER2
    • Trastuxumab: first line
    • Lapatinib: 2nd line (targets EGFR as well)
  19. Anthracycline drugs
    • Doxorubicin
    • Epirubicin
    • Daunorubicin
  20. Aromatase Inhibitors
    • Nonsteroidal: letrozole, anastrozole
    • Steroidal: exemstane
  21. Nonsteroidal Aromatase Inhibitors
    • reversible
    • noncovalent complex w/iron in the heme
    • competitive inhibitors of aromatase
    • pregnancy category X
  22. Steroidal Aromatase Inhibitors
    • forms covalent bond
    • results in irrversible inhibition of aromatase
    • suicide inhibitor
    • prenancy category D
  23. Aromatase Inhibitor adverse effects
    • hot flashes
    • vaginal dryness
    • bone mineral density
    • myalgias
    • diarrhea
  24. Chemotherapy standard of care for breast cancer
    • doxorubicin & cyclophosphamide: 3 months followed by
    • paclitaxel & tratuzumab: 3 months, 12 months respectively

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