Thatcher - Breast Cancer Flashcards
Types of Breast Cancer:
Triple Negative Cancer
- 13 Different Diseases
- but 1 group, different underlying CAUSES
- Only 1 type of treatment = Radiation / Chemotherapy
Types of Breast Cancer:
HER2 Cancer
GF Receptors
- Treatment = HER-2 Inhibitors
- herceptin = Antibodies
- With or withought chemotherapy
Types of Breast Cancer:
Luminal A
ER+ / PR+ / Her2+
45%, bost prevelant type
- Treatment: Endocrine Therapy
Types of Breast Cancer:
Luiminal B
ER+, PR+, Her2+/lowKi67 or Her2-/highKi67
- Treatment = Hormone (endocrine) Therapy
ER-alpha
Estrogen Receptor discovered in 1958
-
ER+ Breast cancer growth & survival driven by the effect of estrogens –> ER-a
- =First drug targets
History of Endocrine Therapy
Clomiphene
- 1950’s MER25 + Clomiphene = First Anti-oestrogens
- Identified as antifertility agents
- 1960’s
- Approved for ovulation induction
History of Endocrine Therapy
Tamoxifen
- 1960’s - Serendipitous discovery
- Tamoxifen ID’ as antifertility agent (contraception)
-
1970’s
- Approved for Treatment for advanced breast cancer
- also Induction of ovulation
- Demonstrated to block Estrogen Receptor
- Approved for Treatment for advanced breast cancer
-
1980’s
- Determed help breast cancer survival
- 1990’s
-
TAMOXIFEN APPROVAL BY FDA
- for reduction of risk of breast cancer
-
TAMOXIFEN APPROVAL BY FDA
History of Endocrine Therapy
Raloxifene
- 1980’s
- ID as anti-oestrogen
-
Used for POST MENOPAUSAL TREATMENTS
- DISCONTINUED AT TREATMENT FOR BREAST CANCER
-
1990’s
- Raloxifine APPROVED BY FDA FOR OSTEOPOROSIS PREVENTION
History of Endocrine Therapy
Fulvestrant
ER Downregulator (SERD)
discovered in 2000’s
- Also discovered serendipitously
- 3rd generation
- Considered as Selective Oestrogen Receptor DOWNREGULATOR
- = SERD
- for POST-menopausal
- “chemo-prevention”
History of Endocrine Therapy
Estrogens / DES
(diethylstilbestrol)
First Discovery as targets of ER in 1950’s
POTENT ER AGONIST
History of Endocrine Therapy
Anastrazole
Discovered in 1990’s
–> POST MENOPAUSAL AROMATASE INHIBITOR
AI’s
Prevents Synthesis of Estrogen
Tamoxifen
(novaldex)
Selective Estrogen Receptor Modulator
SERM
- Discovered serendipitously in 1970’s as post-coital contraceptive
- Effective against endocrine dependent breast cancer = ER+
- Antagonist in Breast
-
Agonist in Endometrium
-
Incidence of OVARIAN CANCER due to this
- positive outweighs negative
-
Incidence of OVARIAN CANCER due to this
Raloxifene
(Evista)
SERM
-
No advantage over tamoxifen in breast cancer
- tumors resistant to tamoxifen were cross-resistant to raloxifene
- does not have agonist activity in endometrium –> possibly less side effects
- Antagonist in breast & endometrium
-
Agonist in BONE
-
–> Repositiones for POST-MENOPAUSAL OSTEOPOROSIS
-
& breast cancer chemoprevention
*
-
& breast cancer chemoprevention
-
–> Repositiones for POST-MENOPAUSAL OSTEOPOROSIS
SERM
MOA
-
Stabilized ANTAGONIST conformation
-
CO-REPRESSOR BINDING –> estrogen receptor
- __collects differents proteins on the dna
-
STILL RESULTS IN TRANSCRIPTION
- but produces DIFFERENT protein products
-
CO-REPRESSOR BINDING –> estrogen receptor
Estradiol MOA
-
Estrogen –> Estrogen Receptor –> Agonist conformation
- = COACTIVATOR COMPLEX
- Collects specific proteins –> DNA
- Transcriptional Activation
- –> Cell survival & Proliferation genes
- –> Breast Cancer
- = COACTIVATOR COMPLEX