Hormonal therapies for breast cancer

Question 1

hormonal therapies for breast cancer work by interfering with estrogen stimulated growth of breast cancer cells

Answer 1

premenopausal women ::: ovaries are primary producers of endogenous estrogen

postmenopausal women + women w/o ovaries ::: adrenal glands primary producers of endogenous estrogen

Question 2

SERM

Answer 2

• selective estrogen receptor modulators
• estrogen antagonist in breast tissue
• estrogen agonist in other tissues, including bone
• for hormone receptor positive breast cancers
• mainly used in post menopausal women
• tamoxifen used in pre- and postmenopausal women and men with breast cancer

Question 3

aromatase inhibitors

Answer 3

• block enzyme for peripheral conversion of adrenally produced estrogen precursors to estrogen
• approved for use in postmenopausal women only
• ineffective in premenopausal women due to estrogen being produced primarily in the ovaries
• occasionally used in premenopausal women but MUST be used in combination with a gonadotropin-releasing hormone (GnRH) agonist to suppress ovarian production of estrogen

Question 4

tamoxifen

Answer 4

• SERM; 20mg PO QD;
• BOXED WARNING: increased risk of uterine or endometrial cancers
• major substrate of 3A4, 2C9, 2D6
• venlafaxine > fluoxetine & paroxetine for hot flashes
• fluoxetine & paroxetine are 2D6 inhibitors
• CONTRAINDICATIONS ::: concomitant warfarin, history of DVT/PE
• SIDE EFFECTS ::: DVT/PE, menopausal symptoms, hot flashes, flushing, weight gain/edema, vaginal bleeding or amenorrhea, arthalgias/myalgias, cataracts, skin changes

MED GUIDE REQUIRED*

Question 5

fulvestrant

Answer 5

• SERM
• 500mg IM days 1, 15, 29 then monthly
• decrease risk of uterine/endometrial cancers?

Question 6

raloxifene

Answer 6

• SERM
• 60mg PO QD
• BOXED WARNING ::: increase risk of thromboembolic events such as VTE, PE, stroke
• CONTRAINDICATIONS ::: history of DVT/PE
• discontinue at least 72 hours prior to and during prolonged immobilization and avoided prolonged restrictions of movement during travel due to increaed risk of blood clots

MED GUIDE REQUIRED

Question 7

anastrozole

Answer 7

Arimidex, 1mg PO QD

• aromatase inhibitor; blocks peripheral conversion of adrenally produced estrogen

Question 8

letrozole

Answer 8

Femara, 2.5mg PO QD

• aromatase inhibitor; blocks peripheral conversion of adrenally produced estrogen

Question 9

exemestane

Answer 9

Aromasin, 25mg PO QD

• aromatase inhibitor; blocks peripheral conversion of adrenally produced estrogen

Question 10

aromatase inhibitors CLINICAL PEARLS & SIDE EFFECTS & CONTRAINDICATIONS

Answer 10

::: CLINICAL PEARLS :::

• higher risk of osteoporosis due to decreased bone mineral density
• higher risk of CVD compared to SERMs

::: SIDE EFFECTS :::

• arthalgia/myalgia, bone pain
• lethargy/fatigue
• menopausal symptoms
• N/V, hepatotoxicity
• HTN, dyslipidemia

::: CONTRAINDICATIONS :::
- pregnancy

Question 11

cyclin-dependent kinase inhibitor

Answer 11

MOA: inhibits downstream signaling and tumor growth

Question 12

pablociclib

Answer 12

Ibrance, 125mg PO QD for 21 of 28 day cycle

cyclin-dependent kinase inhibitor

• use with letrozole/fulvestrant significantly improves outcomes
• take with food
• avoid CYP3A4 inhibitors/inducers

SIDE EFFECTS :::

• myelosuppression (mild)
• N/V/D
• thromboembolic events (PE)
• fatigue
• alopecia
• infection
• blurred vision