Pharm 1: Endocrine Therapies used in Breast Cancer

Question 1

What must you do before you start Endocrine Therapies used in Breast Cancer ?

Answer 1

• Make sure the patient is estrogen receptor +

o Endocrine therapy is the treatment of choice for patients with hormone receptor-positive tumors who exhibit the first sign of metastatic disease in soft tissue, bone, or pleura.

Question 2

What are the goals of Endocrine therapy?

Answer 2

• Decrease circulating levels of estrogen
• Prevent the effects of estrogen at the breast cancer cell (targeted therapy) by blocking the hormone receptors or down regulating the presence of those receptors.

Question 3

Aromastase Inhibitors
examples:
MOA:

Answer 3

• Examples: Anastrozole, Letrozole, and Exemestane
• MOA: block the binding of estrogen to the receptor
o Aromatase is responsible for peripheral conversion of androstenedione, produced by the adrenal gland, into estrone and estradiol.

Question 4

Aromastase Inhibitors
nonsteroidal compounds
steroidal
first line therapy for advanced Breast CA in post-menopauseal women

Answer 4

• nonsteroidal compounds : Anastrozole and letrozole are nonsteroidal compounds that exhibit reversible, competitive inhibition of aromatase while
• Exemestane is steroidal and irreversible.

•Anastrozole and letrozole are for first-line therapy indicated for advanced breast cancer in postmenopausal women. Uterine cells will stop producing the estrogen at this point so it will target the other cells

Question 5

Antiestrogens 
MOA: 
SERMs and Pure antiestrogen
-SERMs:
-Pure Antiestorgens:

Answer 5

• MOA: Binds to estrogen receptors, which inhibit receptor-mediated gene transcription and therefore block the effect of estrogen on the end target

SERMs and pure antiestrogens
o SERMs include tamoxifen and toremifene (and raloxifene for breast cancer risk reduction in high-risk women. They inhibit cell proliferation in breast cells, but stimulate the proliferation of uterine endometrial cells.
o Pure antiestrogens also called selective estrogen receptor downregulators (SERDs). These molecules bind to the ER, inhibit estrogen binding, and degrade the drug-ER complex, thus decreasing the amount of ER on the tumor cell surface. Fulvestrant is the only drug in this class

Question 6

LHRH analogs: LH releasing Horome(same thing as GNRH)
MOA:

Three agents:

• Goserelin is approved for the treatment of

• Indicated for
• What is a side effect of LHRH analogs?

Answer 6

• MOA: It down regulates LHRH receptors in the pituitary resulting to decreased levels of luteinizing hormone. This subsequently lead to a decrease in estrogen to castrated levels.

o Thus the effect of LHRH analogs on circulating estrogen levels in premenopausal breast cancer simulates oophorectomy.

(3) leuprolide, goserelin, and triptorelin.

• Goserelin is approved for the treatment of metastatic breast cancer.
• Indicated for premenopausal women with breast cancer

• What is a side effect of LHRH analogs?
o Hot flashes