Hormonal Modulation of Cancer Flashcards
Tamoxifen - MOA?
Reduces estrogen related DNA synthesis.
Upregulates TGFb and downregulates ILGF1 (which stimulated breast growth)
Tamoxifen - target?
ER α / β
Raloxifen - target?
ER α-antagonist
Raloxifen - MOA?
Reduces estrogen related DNA synthesis.
Upregulates TGFb and downregulates ILGF1 (which stimulated breast growth)
Tamoxifen - AEs?
Hot flushes, vaginal dryness, risk for endometrial cancer, DVT
(inhibits osteoclasts so protects bone)
Raloxifen - AEs?
Hot flushes, vaginal dryness, risk for endometrial cancer, DVT , Bone loss
Leuprolide - MOA?
Analogue of gonadotropin releasing hormone
- Binds receptors in continous fashion → ↓ FSH & LH production
- ↓ Testosterone production in men to castration levels
- ↓ Estrogen in women
Leuprolide - AEs?
- Hot flushes (severe)
- Bone loss
- Vaginal dryness
Anastrozole - MOA?
Blocks Aromatase (reversible)
Anaztrozole - AEs?
Hot flushes, GI disturbance, headache, musculoskeletal pain, bone loss , urogenital disorders (lower risk of DVT and no endometrial cancers)
ER-α locations?
Endometrium, myometrium, breast cancer cells, breast ducts, ovarian stromal cells, hypothalamus, epithelium of the efferent ducts
ER-β locations?
Kidney, brain, bone, heart, lungs, intestinal mucosa, prostate, endothelial
What do you say?
Your 73 year old great Aunt has breast cancer that is estrogen and progesterone receptor positive, Stage I wants to know if she should take anastrozole suggested by her primary care doctor.
There are many factors that are taken into consideration regarding the risk for recurrence (aside from this info). Additionally the use of tamoxifen first and then anastrozole second or anastrozole alone first remains controversial. One of the significant things you have seen is that each drug has a different set of side effects and this must also be taken into consideration in the choice. The cardiac, thromboembolic, bone, and other risks must be matched to the patient. In general your answer is yes.
What do you say?
Your 70 year old Grandfather is found to have metastatic, AR positive prostate cancer and wants to know what you think about his taking “hormones” to treat it.
Given your understanding of the high rate of receptors in prostatic cancer, and with the information that there is a high rate of initial response and somewhat lesser risks to hormonal modulation with prostate cancer, you would be supportive of this approach.
Your 38 year old cousin has a high BMI and now has early endometrial cancer. She has no children and wants to keep her uterus. Her doctor has suggested that she use a progesterone containing IUD and take oral progesterone as well. Do you think this might work?
This is a very controversial area where studies are limited and long term follow up is limited. The use of high dose progestins orally with a progesterone containing IUD presently appears to be the strongest approach but there is a significant rate of failure to resolve the cancer (at least 25%). Consider that while hormonally sensitive, to be a cancer mutations must already be in place, so this course of treatment should be considered very carefully with planned endometrial biopsies or hysteroscopy to evaluate the response.
