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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
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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
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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
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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
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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
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Anthracycline Toxicity
- acute: arrhythmias
- chronic: heart failure
- *treat w/ dexrazoxane
- myelosuppression (dose-limiting)
- mucositis
- emesis
- diarrhea
- alopecia
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Anthracycline Lifetime dose limits
- doxorubicin: 550mg/m2
- daunorubicin: 1000mg/m2
- epirubicin: 900 mg/m2
- *doxorubicin @300mg/m2 treat w/ dexrazoxane
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Anthracycline IV extravasates treatment
- dimethyl sulfoxide
- dexrazoxane (totect)
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Vinorelbine adverse effects
- alopecia
- GI (constipation, diarrhea, emesis)
- injection site reactions
- leukopenia (dose-limiting)
- peripheral neuropathy
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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
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Trastuzumab adverse effects
- cardiotoxicity: heart failure
- infusion related toxicity: ferver, chills, nausea, rash, dyspnea
- *pretreatment w/ APAP & diphenhydramine (for infusion related toxicity)
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Lapatinib adverse effects
- hand-foot syndrome
- rash
- diarrhea
- fatigue
- elevated LFTs
- heart failure
- black box warning: impaired liver funtion
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Tamoxifen drug-drug interactions
- fluoxetine
- bupropion
- paroxetine
- substitutes: citalopram, venlafaxine, excitalopram
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Tamoxifen adverse effects
- hot flashes
- irregular menses
- vaginal bleeding
- uterine malignancies
- stroke
- pulmonary embolism
- category X
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Fulvestrant adverse effects
- hot flashes
- headache
- nausea
- injection site pain
- category D
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Selective Estrogen Receptor Modulators (SERM)
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Selective Estrogen Receptor Downregulators (SERD)
Fluvestrant
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Drugs targeting HER2
- Trastuxumab: first line
- Lapatinib: 2nd line (targets EGFR as well)
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Anthracycline drugs
- Doxorubicin
- Epirubicin
- Daunorubicin
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Aromatase Inhibitors
- Nonsteroidal: letrozole, anastrozole
- Steroidal: exemstane
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Nonsteroidal Aromatase Inhibitors
- reversible
- noncovalent complex w/iron in the heme
- competitive inhibitors of aromatase
- pregnancy category X
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Steroidal Aromatase Inhibitors
- forms covalent bond
- results in irrversible inhibition of aromatase
- suicide inhibitor
- prenancy category D
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Aromatase Inhibitor adverse effects
- hot flashes
- vaginal dryness
- bone mineral density
- myalgias
- diarrhea
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Chemotherapy standard of care for breast cancer
- doxorubicin & cyclophosphamide: 3 months followed by
- paclitaxel & tratuzumab: 3 months, 12 months respectively
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