Breast Cancer pt3 – Flashcards

SERM 20mg QD Antagonism on breast tissue Estrogen agonist effects on bone, lipids and the endometrium active metabolites (endoxifen and 4-OH tamoxifen)

SE: Thromboembolism, Endometrial cancer, risk of bleeding with warfarin (INR)

SERM Benefit of osteoporosis Newer SERM which have the same effects as tamoxifen but not the same effects on the endometrium, used for prevention (IT IS NOT USED FOR TREATMENT) only for PREVENTION

SE: Thromboembolism

Non-steroidal anti-estrogen/pure anti-estrogen

LD then every 1 month as MD (loading and then maintenance)

Non-steroidal aromatase inhibitor SE: Musculoskeletal disorder (myalgia, arthralgia), osteoporosis, fracture, vaginal bleeding

Steroidal Aromatase Inhibitor SE: Musculoskeletal disorder (myalgia, arthralgia), osteoporosis, fracture, vaginal bleeding

Tamoxifen (20mg QD prevention and tx) Raloxifine Toremifene

Fulvestrant

Properties • competitive inhibitor for estrogen-binding receptor • used in hormone receptor positive • used for 5-10 years post surgical, radiation and chemotherapy • Tamoxifen is a "SERM (Selective Estrogen Receptor Modulator)" which has antagonism on breast tissue but has estrogen agonist effects on bone, lipids and the endometrium • Raloxifene is a newer SERM which have the same effects as tamoxifen but not the same effects on the endometrium, used for prevention (IT IS NOT USED FOR TREAMENT) • Fulvestrant (Faslodex) is a "pure antiestrogen." IM use • Cross-resistance does occur

Usage used for 5-10 years post surgical, radiation and chemotherapy

ADR • Thromboembolism • Deep vein thrombosis • Pulmonary embolus • Thrombotic stroke • Transient ischemic attack • Endometrial cancer risk (only with Tamoxifen) • osteoporosis (only with Tamoxifen: estrogen agonist or antagonist in bone) • retinopathy and cataract formation (only with Tamoxifen) • Menopausal symptoms: • hot flashes • weight gain • menstrual irregularities • headache • mood swings

ADR Osteoporosis Retinopathy and cataract formation

DDI o Tamoxifen has active metabolites (endoxifen and 4-OH tamoxifen) o Co-administration of strong inhibitor of CYP2D6 should be used with caution. o Some SSRIs like fluoxetine and paroxetine decrease the formation of active metabolites of tamoxifen and may impact its efficacy. o However, citalopram and venlafaxine appear to have minimal impact on tamoxifen metabolism. o Based on current data the NCCN panel recommends AGAINST CYP2D6 testing for women being considered for tamoxifen therapy.

Fluoxetine/Paroxetine use caution Venlafaxine/Citalopram minimal metabolic impact

Anastrozole (Arimidex) - tx Letrozole (Femara) - tx Exemestane (Aromasin) - tx and prevention Used in postmenopausal women only

• It should be used in postmenopausal women. (It is not active in the treatment of women with functional ovaries and should not be used in women with intact ovarian function) • a major source of estrogen is derived from peripheral androgen conversion which requires aromatase • blocking this enzyme reduces the level of circulating and glandular estrogen by blocking adrenal androgen to estrone conversion in peripheral tissue • in post-menopausal women estrogen concentrations in breast tissue may be as much as 10 times greater due to peripheral aromatization

Adverse Reactions • Bone loss (unlike antiestrogens), consider bisphosphonates (Ca + vit D • Musculoskeletal disorder (i.e. arthralgia) (> antiestrogens) • tumor flare • menopausal symptoms: hot flashes, weight gain, menstrual irregularities, headache, mood swings (<antiestrogens) • flu-like symptoms

BONE LOSS (consider bisphosphonates) MUSCULOSKELETAL DISORDER

A single study (BOLERO-2) in women with hormone receptor positive, Her2(-), and prior therapy with a non-steroidal aromatase inhibitor demonstrated improvement in time to progression with the addition of everolimus to exemestane and with increase in toxicity. No overall survival differences

Goserelin (Zoladex) and Leuprolide acetate (Lupron) are only agents for breast cancers Used for pre-menopausal pt whose ovary function is still functional

The emerging evidences have shown that ovarian suppression with GnRH agonist therapy during adjuvant chemotherapy in premenopausal women may preserve ovarian function and diminish the likelihood of chemotherapy-induced amenorrhea

All premenopausal pts should be informed of changes in fertility prior to chemo Amenorrhea can happen; most women younger than 35yo resume menses in 2 years Menses ≠ fertility. you can have menses and be infertile, you can not have menses and still be fertile Hormone-based birth control discouraged regardless of receptor status in cancer Ovarian suppression with GnRH in ER(-) pt diminished likelihood of chemo-induced amenorrhea Breast feeding after chemo is okay although nutrients may be lacking, but do not do so during chemo treatment ER(+) disease pt have conflicting reports with GnRH agonist therapy on fertility

CAF or FAC (cyclophosphamide, doxorubicin, fluorouracil) FEC and CEF (fluorouracil, epirubicin, cyclophosphamide) AC +/- taxanes sequential (Cyclophosphamide, doxorubicin)

cyclophosphamide, doxorubicin, fluorouracil

fluorouracil, epirubicin, cyclophosphamide

Cyclophosphamide, doxorubicin

(doxorubicin/cyclophosphamide followed by paclitaxel/trastuzumab +/- pertuzumab)

AC --> TH +/- P (doxorubicin/cyclophosphamide followed by paclitaxel/trastuzumab +/- pertuzumab)

Cyclophosphamide, Methotrexate, Fluorouracil

Given for 4-6 cycles as a complete therapy

Can use tamoxifen for 5 years (can extend to 10 years) Can add ovarian suppression (LHRH analogue) - when used, person will become menopausal, which allows use of aromatase inhibitors

Tamoxifen or Aromatase Inhibitor Concert Tamoxifen (5 years) then aromatase inhibitor