specific cancers

What syndrome results in males having 1 Y chromosome and ≥2 X chromosomes resulting in more estrogen?

Klinefelter syndrome

What is the normal role of BRCA1 and BRCA2 genes?

DNA repair genes

Breast cancer prevention

HR+ breast cancer TX

• PRE-MENO: tamoxifen or AI + ovarian ablation/suppression

• POST-MENO: tamoxifen or AI

SERM MOA & example

• Selective Estrogen Receptor Modulators that compete at receptor binding sites in breast and other tissue

• Tamoxifen

Tamoxifen BW

Increased risk of uterine or endometrial cancer and thromboembolic events

Tamoxifen adverse effects (3)

• Hot flashes/night sweats

• Vaginal bleeding/discharge

• Decreased bone density (supp with Ca/Vit D)

Tamoxifen indcation

• HR+ breast cancer

SERD MOA & drugs

• Selective estrogen receptor degrader: estrogen receptor antagonist that causes receptor downregulation

• Fluvestrant IM injection

Fluvestrant indication

HR+ breast cancer treatment

AI MOA & drugs

• Aromatase inhibitor: blocks peripheral conversion of androgens to estrogen

• Anastrozole (arimidex)

HER 2+ treatment

Trastuzumab

T/F: most prostate cancers can be felt with a digital rectal exam

True

What is ADT?

• Androgen deprivation therapy or chemical castration

GnRH AGONISTs MOA & drugs

• aka LHRH

• They cause an initial surge in testosterone, followed by a gradual reduction through a negative feedback mechanism

• Leuprolide (Lupron), Goserelin (Zoladex)

- Used in combo with antiandrogen like bicalutamide to prevent the tumor flare

Leuprolide adverse effects (5)

• Hot flashes

• Impotence

• Gynecomastia

• Bone pain (risk of osteoporosis)

• QTC prolongation

GnRH ANTAGONISTS MOA & drugs

• Block GnRH receptors directly causing a rapid decrease in testosterone production

• Relugolix, Degarelix

• No tumor flare!

ANTI-ANDROGENS MOA & drugs

• Competitively inhibits testosterone from binding to prostate cancer cells

• Bicalutamide (Casodex)

Abiraterone MOA

• Interferes with CYP17 enzyme involved in the synthesis of steroid hormone in the testes and adrenal glands to decrease testosterone production