Breast Cancer Drugs Flashcards
(39 cards)
Which breast cancer drugs are specifically for premenopausal women?
GnRH agonists (Leuprolide)
*Biologics and SERMs can be used for pre and postmenopausal women
Which breast cancer medications are specifically for postmenopausal women?
Aromatase inhibitors (they are not effective in premenopausal women.
*Toremifene (SERM) is better than tamoxifen in postmenopausal women. Biologics can be used in both pre and postmenopausal patients.
Describe the mechanism of action of SERMs (tamoxifen and toremifene) and identify the primary distinction between these two medications.
They block estrogen binding to ER-alpha/beta in breast cancer cells preventing transcription of pro-proliferative and pro-survival genes, and may result in apoptosis from inhibiting survival gene transcription.
*Toremifene does not require CYP2D6 activation but tamoxifen does
Describe the pharmacokinetics of tamoxifen.
It is a prodrug that is activated by CYP2D6, creating active metabolites 4-hydroxyTAM and endoxifen (the ER-alpha/beta antagonists). The rate-limiting step in endoxifen formation is CYP2D6 in the liver.
Discuss the efficacy of tamoxifen versus toremifene (both SERMs).
They are equally efficacious, but tamoxifen requires metabolism via CYP2D6 and toremifene does not.
What drugs should be avoided while taking tamoxifen?
Any drugs with strong CYP2D6 inhibition, such as SSRIs.
Discuss pharmacogenetic testing in the context of tamoxifen use.
Conflicting studies have caused the FDA to recommend (in 2006) and then stop recommending (in 2010) genetic testing for the activity of CYP2D6 in patients going on tamoxifen b/c it may or may not have significant effects on medication response depending on enzyme activity. Controversial.
Which breast cancer drug classes cause menopausal side effects such as hot flashes and osteoporosis?
SERMs, GnRH agonists, and aromatase inhibitors
What risks increase with tamoxifen and toremifene use?
There is increased risk for endometrial cancer with both drugs. Tamoxifen specifically increases risk for DVT and PE, and the increased risk of endometrial cancer is 4-6x with tamoxifen use >= 5 years
Why do clinicians typically limit tamoxifen use to 5-10 years?
It increases risk of endometrial cancer significantly after 5 years of use, and patients generally begin developing resistance at 5 year mark
When is tamoxifen use contraindicated?
In pregnancy.
In pts w/ hx of DVT or PE (UNLESS they have invasive cancer, b/c then benefits outweigh risks for clot).
What are the clinical indications for tamoxifen?
Pre and postmenopausal ER positive breast cancer ranging from DCIS to metastatic, and for prevention in high-risk individuals.
What are the clinical indications for toremifene?
It is a better choice in the SERM drug class for postmenopausal women with ER+ breast cancer, but is not approved for early stage dz (e.g. DCIS) or risk reduction like tamoxifen
What are the contraindications for toremifene?
Like tamoxifen, it is contraindicated in pregnant pts or those w/ hx of DVT
What are the clinical indications for GnRH agonists (leuprolide)?
Premenopausal ER+ breast cancer and prostate cancer. Used as adjuvant therapy in metastatic ER+ breast cancer and prostate cancer.
*It is NOT considered best option for early stage breast cancer and tamoxifen should be considered first.
With which drug classes can leuprolide (GnRH agonist) be combined?
With SERMs for breast cancer treatment, or with androgen receptor antagonists for prostate cancer.
Describe the mechanism of action of leuprolide.
It is a GnRH receptor agonist in the pituitary that disrupts normal pulsatile stimulation of endogenous GnRH, resulting in down-regulation/desensitization of GnRH receptors leading to decreased LH and FSH release and thus decline in estrogen and progesterone synthesis by ovaries or testosterone by testes.
In addition to hot flashes and osteoporosis, what other side effect is associated with leuprolide?
Sexual dysfunction.
*b/c this medication decreases LH and FSH release, it decreases testosterone and estrogen which play a key role in libido and sexual function
When is leuprolide contraindicated?
During pregnancy
What transient effect should you be aware of when starting leuprolide?
Transient increase in LH and FSH and thus transient increases in estrogen/testosterone and thus transient worsening of cancer symptoms.
Name the aromatase inhibitors and their mechanism of action.
Anastrozole and exemestane. They prevent the conversion of testosterone to estrogen by inhibiting aromatase (CYP19A1) in adipose tissue.
What is the primary difference between anastrozole and exemestane in terms of mechanism?
While they are both aromatase inhibitors, anastrozole is a reversible inhibitor and exemestane is not.
What are the clinical indications for aromatase inhibitors?
Postmenopausal early stage or metastatic ER+ breast cancer. They can be used as adjuvant monotherapy up to 5 years or sequentially (i.e. 5 years tamoxifen followed by 5 years on an AI)
Why aren’t aromatase inhibitors effective in premenopausal women?
Because the hypothalamic-pituitary-gonadal axis can overcome the effects of AIs, but after menopause the primary source of low estrogen levels is adipose tissue
