antiestrogens to treat breast cancer Flashcards
protective factors against breast cancer
reduced estrogen/progesterone exposure
lactation
early age for first pregnancy
exercise
risk factors for breast cancer
why?
increased exposure to estrogen/progesterone early menarche late menopause obesity (postmenopausal) HRT
why? –> E stimulates TGFalpha production and TGF alpha causes breast cell proliferation
treatment for postmenopausal , ER-negative
a high risk group
treat w chemo
treatment for postmenopausal, ER positive
tamoxifen, raloxifene, or aromatase inhibitor alone or w chemo
high risk - same three with chemo
treatment for premenopausal, ER negative
a high risk group
treat w chemo
treatment for premenopausal, ER positive
tamoxifen, raloxifene, alone or with chemotherapy, or GnRH agonist
if high risk, chemo plus tamoxifen or raloxifene with GnRH agonist
if HER2 is expressed, breast tumor is considered high risk and is treated with
chemo, trastuzumab and an antiestrogen if ER positive
three genetic changes common to breast cancer
- P53 mutations in Li-Fraumeni syndrome
- BRCA1- familial female breast & ovarian cancer
- BRCA2-familial female & male breast cancer
after metastasis begins, the only way to treat disseminated cells is
chemotherapy
three antiestrogens
tamoxifen
raloxifene
fulvestrant
tamoxifen
a SERM, competitive partial agonist-inhibitor —-prevents estrogens binding to ER (e receptor)
• Sometimes can induce estrogen-like effects; initially acts as antagonist in breast tissue but as an agonist in endometrial tissue
• Oral drug; activated by CYP2D6; has LONGER half-life than estradiol
• Reduces recurrence of breast cancer; most useful in high risk postmenopausal women with ER+ breast cancer
- Not effective in ER- cancer or premenopausal women
- One of the least toxic antineoplastic agents!
- Side effects: hot flashes, endometrial carcinoma (E agonist in the uterus), thromboembolic events (E agonist increases clotting factors and decreases antithrombin 3), drug drug itxn (don’t use with SSRIs (fluoxetine for depression) since they inhibit CYP2D6)
- Other benefits: reduces total cholesterol and preserves bone density
why stop using tamoxifen after 5 years?
ONLY use up to 5 years after 5 years, it will begin to act as a partial agonist in breast tissue
raloxifene
a SERM
• As effective as tamoxifen in preventing breast cancer with FEWER side effects LOWER incidence of uterine cancer and blood clots!
• Very low toxicity – hot flashes, N/V, less likely thromboembolic events and endometrial carcinoma
Fulvestrant
– a true estrogen receptor antagonist; has no estrogen agonist effects
• Use for postmenopausal women whose cancer doesn’t halt with tamoxifen or raloxifene
Anastrozole, Letrozole, and Exemestane
Selective and irreversible aromatase inhibitors
– (have little/no effect on mineralocorticoid or glucocorticoid synthesis); continue to be effective past 5 years! And no risk of endometrial cancer or thromboembolic events!! VERY effective; approved for first line therapy as alternative to tamoxifen
• Anastrozole – as effective as tamoxifen for advanced breast cancer; fewer and less severe hot flashes
