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61 Cards in this Set

  • Front
  • Back
what is the most common cancer in women? Etiology
Breast Cancer
180,000 new cases/yr
45,000 deaths/yr
Lifetime risk of development of breast cancer?
1 in 8
Which two hormones are important in the etiologies of breast cancer?
Risk factors assoc. w/increased exposure to estrogen and progesterone
Early menarche
Late menopause
Obesity (postmenopausal)
Protective factors assoc. w/decreased estrogen and progesterone
Early age @ first full term pregnancy
Genetics associated w/breast cancer
p53 mutations in Li-Fraumeni syndrome, less than 1%
BRCA-1 mutation in familial breast and ovarian cancer
BRCA-2 in familial female and male breast cancer
Breast cancer treatments
Surgical removal of the tumor and axillary lymph nodes
Radiation therapy
Adjuvant drug therapy
Adjuvant Drug therapy for breast cancer
Doxorubicin and analogues
Therapy after metastasis
Chemo only
ONLY 10-20% remission
Name two anti-estrogen drugs
Tomoxifen MOA
Competitive partial agonist-inhibitor think of as a functional competitive receptor antagonist

Prevents estrogen binding to estrogen receptor
Tamoxifen's affinity for the estrogen receptor
10 fold lower than estrogen
PK of Tamoxifen
Well absorbed after oral admin
Eliminated in feces and some in urine
Two phase elimination
Describe Tamoxifen's two phase elimination
1st phase- t1/2 = 7-14 hours
2nd phase- t1/2 = 7-14 days

The point: much longer t1/2 than estradiol
Dosing of Tamoxifen
2X daily of 10mg for 2-5 years.
Stats for Tamoxifen-
Risk reduction
Reduces recurrence by 30% and death by 20%
When used in combo risk reduced by another 30%
Who is Tamoxifen most useful in?
Post-menopausal women w/estrogen receptor (+) breast cancer
What treatment is best for premenopausal women or those w/estrogen receptor poor tumors?
Adverse Rxns to Tamoxifen
*considered one of the least toxic drugs
Hot flashes
Nausea and vomiting
Vaginal bleeding
Endometrial carcinoma
Thromboembolic events
How can we prevent the hot flashes in women taking Tamoxifen?
Megestrol or SSRIs (again!)
Tamoxifen and prevention
Reduces risk of breast cancer by 45% in healthy women who are at High Risk for breast cancer
Potential beneficial side effects of Tamoxifen
Reduces total cholesterol and preserves bone density in postmenopausal women
*Due to estrogen like effects
Possible lower incidence of uterine cancer
Name a true estrogen receptor antagonist
How do you give Fulvestrant?
Who do you give it to?
Once a month i.m.
Postmenopausal women whose cancer progresses on tamoxifen or other anti-estrogen
Name 3 aromatase inhibitors
Who do you use aromatase inhibitors on?
Postmenopausal women whose cancer progresses despite tamoxifen treatment
Aminoglutethimide MOA and specificity (take a deep breath)
(-) one of the P450 enzymes that converts cholesterol into pregnolone--> all classes of cholesterol reduced

Also (-) conversion of androstenedione--> estrone and estradiol in the peripheral tissues by the aromatase enzyme
PK of Aminoglutetimide
Administered orally
t1/2 = 10-20 hours
Clinical use for aminoglutetimide
2nd line (after tamoxifen) for metastatic breast cancer
Dosing for aminoglutetimide
125 mg 2X/day
increase 250 mg 2X/day with 20 mg hydrocortisone (compensates for its steroid synthesis inhibition)
Adverse Rxn of Aminoglutetimide
Blurry vision
Maculopapular rash
Which drug Tamoxifen or Aminoglutetimide yields adverse rxns more often.
Anasterozole and Letrozole
Nonsteroidal aromatase inhibitors, doesn't have the mineral and glucocorticoid effect
Can Anasterozole be used as 1st line therapy
Name 2 progesterone agonists
Dosage of Megesterol/
160 mg/day for treatment of advanced breast cancer
SE of progesterone agonists?
How can that be used effectively?
Stimulate apetite--wt. gain
Used to treat anorexia/cachexia related to cancer and AIDS
Name two Gonadotropin-releasing hormone agonists
MOA of Leuprolide and Goserelin (yup, deep breath again)
GnRH agonists w/increase affinity
Induce intial gonadotropin release (2-4 wks)
After flare FSH and LH cells get desensitized and plasma estradiol and progesterone levels.
Admin of Leuprolide and Goserelin
i.m. or s.c. in a parenteral sustained microcapsule prep.
Clinical use of Leuprolide and Goserelin
Metastatic breast cancer in PREMENOPAUSAL women

MAIN USE: Prostate cancer
Adverse Rxns to Leuprolide and Goserelin
Hot flashes
*due to ablation of sex hormones
Herceptin (aka trastuzumab)
A humanized monoclonal Ab agonist against the HER2/erbB2 receptor

*HER2/erbB2 recetptor is overexpressed (25-35%) in breast cancer
What family of receptors does the HER2/erbB2 receptor belong to?
Epidermal growth factor receptor family
Stats for prostate cancer
New cases/deaths/lifetime risk
Most common cancer in men- 240,000 new cases/yr
40,000 deaths/yr
lifetime risk is 1 in 6
Etiology of Prostate cancer
Main risk factor is AGE
Rare prior to age 40
(+) correlation between testosterone levels and risk
Mutations in androgen receptor gene may play a role
Treatment for prostate cancer
Surgical removal
Radiation therapy
Hormonal therapy for advanced dz
Deferred therapy
Watchful waiting, treatment postponed until tumor becomes symptomatic

*Important in elderly individuals when you're weighing expected lifespan with quality of life after surgery
Prevention of Prostate Cancer
50 I.U./day of Vit. E~ reduce risk by 1/3
150-200 mcg/day selenium~ reduce risk by 2/3
Lycopene (red pigment in tomatoes) also reduces risk
Different kinds of Hormone Therapy for Prostate Cancer
1. Nonsteroidal antiandrogens
2. Steroidal antiandrogens
3. Gonadotropin-releasing hormone agonists
4. Adrenal Enzyme synthesis inhibitors
Non-steroidal antiandrogens
MOA of Flutamide
Prevents binding of DHT to its receptor
PK and admin of Flutamide
Orally 3X/day because of short t1/2 (7-8 hours)
Clinical use for Flutamide
Metastatic prostate cancer
Adverse Rxns of Flutamide
Diarrhea (most common)
Gynecomastia (give drug w/GnRH inhibitor)
Hepatotoxicity (rare)
More recent nonsteroidal antiandrogen
May be more effective than Flutamide
Name two steroidal antiandrogens
*except the intrinsic steroidal side effects
Name two Gonadotropin-releasing agonists
*note equivalent antitumor effect as surgical castration or diethylstilbestrol treament.
Adrenal enzyme synthesis inhibitors, MOA, use
Ketconazole~ antifungal drug
(-) P450 enzymes involved in steroid synthesis
Good 2nd line agent