Treatment of Breast & Endometrial Cancer Flashcards
Aromatase Inhibitors Drugs:
Anastrozole
Letrozole
Exemestane
SERDs & SERMs Drugs:
Raloxifene
Tamoxifen
Toremifene
Fulvestrant
HER-2/neu Antibodies Drugs:
Pertuzumab
Trastuzumab
Ado-Trastuzumab Emtasine
TKI Drugs:
Lapatinib
GnRH Agonist Drugs:
Goserelin
mTOR Inhibitor Drugs:
Everolimus
BRCA1 & BRCA2 Function:
Tumor suppressors involved in repair of double strand breaks.
PIK3CA Function:
Catalytic subunit of PI3 kinase; key signal transduction enzyme involved in cellular growth, survival and insulin signaling.
TP53 Function:
Tumor suppressor; key regulator of cell cycle, DNA repair, apoptosis.
GATA3 Function:
Transcription factor which regulates luminal epithelial cell differentiation in the mammary gland.
MAP3K1 Function:
Kinase that activates ERK and JNK kinase pathways.
MLL3 Function:
Histone-lysine N-methyltransferase involved in transcriptional co-activation.
Options for Mutant BRCA1/2 Carriers Prophylactic
Mastectomy and bilateral salpingo-oophorectomy (BSO) in order to decrease the risk of breast and ovarian cancer.
Bilateral mastectomy decreases breast cancer risk by?
90%
Options for Mutant BRCA1/2 Carriers Chemoprevention?
tamoxifen or raloxifene
Prospective study indicates 50% reduction in risk for BRCA2 mutation carriers but no effect for BRCA1 carriers. Why?
- 60-75% BRCA2-tumors are ER+
* 70-90% of BRCA1-tumors are ER-
Clinical features that warrant referral for genetic
testing for BRCA1/2 mutations?
- Early-onset breast cancer, (< age 50 or 45)
- Ovarian, fallopian tube or primary peritoneal cancer
- Individuals with 2 or more primary breast cancers, or breast & ovarian cancer in the same individual
- Male breast cancer
- 2 or more individuals in the family with breast and/or ovarian cancer
- Ashkenazi Jewish ancestry
A significant number of patients with ER- or PR-positive tumors
Respond to hormonal therapy. Clinically response in 8 to 12 weeks to detect.
Anti-estrogen therapy includes:
Selective Estrogen Receptor Downregulators (SERDs)
Selective Estrogen Receptor Modulators (SERMs)
Aromatase Inhibitors (AI)
Fulvestrant Mechanism:
Pure antagonist; no estrogenic actions.
Impaired dimerization, increased turnover, disrupted nuclear localization, degradation leading to decrease ER levels.
Fulvestrant used in treatment for?
For ER+ metastatic BC in PM women with disease
progression following anti-estrogen therapy.
Fulvestrant
Administer:
Metabolism:
Side Effects:
Monthly IM: sustained plasma levels Hepatic metabolism; no drug interactions Adverse effects – PM symptoms – Nausea, asthenia, pain, vasodilation (hot flashes), & headache
Fulvestrant Failure of therapy
Estrogen-independent cell growth
Tamoxifen & Raloxifene Mechanism:
ER agonist/antagonist
– Location of ER subtypes (α and β)
– Estrogen effect on bone
– Anti-estrogen effect on mammary tissue
Tamoxifen Dosage:
Daily PO [Tam]
Raloxifene Doseage:
Monthly IM [Ral]
Tamoxifen & Raloxifene Effects:
– Decrease bone metabolism (Increase bone mineral density)
– Decrease serum cholesterol, LDL, lipoproteins, and Increase apolipoprotein-A1
Tamoxifen & Raloxifene High dosage causes?
– Retinal degeneration at high doses
– Teratogens
Tamoxifen BBW:
Endometrial hypertrophy, vaginal bleeding, endometrial cancer. Thromboembolic disease (DVT or PE), Stroke.
Raloxifene BBW
Thromboembolic disease (DVT or PE), Stroke.
Toremifene Mechanism:
Derivative of tamoxifen with antiestrogenic properties.
Toremifene Dosage:
PO Daily; CYP3A4 metabolism (no active products)