Course Content
Module 1 — Principles of Hormone Therapy in Oncology
Mechanism and Dosing Overview Aromatase Inhibitors (AIs): block the enzyme aromatase (CYP19A1), which converts androgens to estrogens in adipose and peripheral tissues. Examples: Anastrozole 1 mg orally daily, Letrozole 2.5 mg orally daily, Exemestane 25 mg orally daily. These are the preferred agents in postmenopausal women with estrogen receptor–positive breast cancer. Selective Estrogen Receptor Modulators (SERMs): such as Tamoxifen 20 mg orally daily — bind the estrogen receptor and act as antagonists in breast tissue but partial agonists in bone and endometrium. Selective Estrogen Receptor Degraders (SERDs): such as Fulvestrant 500 mg intramuscularly on days 0, 14, 28, then every 28 days thereafter — promote estrogen receptor degradation. CYP17 Inhibitors: Abiraterone acetate 1000 mg orally daily on an empty stomach plus Prednisone 5 mg orally twice daily — block the CYP17A1 enzyme, suppressing androgen synthesis in adrenal glands and tumors. Gonadotropin-Releasing Hormone (GnRH) Agonists and Antagonists: Leuprolide 7.5 mg subcutaneously every 4 weeks or depot every 3–6 months; Degarelix 240 mg subcutaneously loading dose, then 80 mg every 4 weeks; Relugolix 120 mg orally daily — suppress testosterone or estrogen production by downregulating or directly blocking pituitary gonadotropin release.
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Hormone Therapy for Cancer Patients: Mechanisms, Indications, and Clinical Practice

Estrogen pathway (breast/endometrium):

Aromatase Inhibitors (AIs) — block aromatase (CYP19A1), reducing estrogen synthesis (postmenopausal setting preferred).

  • Anastrozole (Arimidex®): 1 mg orally once daily.

  • Letrozole (Femara®): 2.5 mg orally once daily.

  • Exemestane (Aromasin®): 25 mg orally once daily (steroidal, irreversible).
    Notes: check bone density; arthralgia common.

Selective Estrogen Receptor Modulator (SERM) — binds ER; antagonist in breast, partial agonist in bone/endometrium.

  • Tamoxifen (Nolvadex®): 20 mg orally once daily.
    Risks: venous thromboembolism, endometrial cancer (post-menopause).

Selective Estrogen Receptor Degrader (SERD) — binds and degrades ER (helps in ESR1 mutations).

  • Fulvestrant (Faslodex®): 500 mg intramuscular on days 0, 14, 28, then every 28 days (alternate gluteal sites).

Androgen pathway (prostate):

GnRH agonists — initial “flare,” then pituitary down-regulation → ↓ LH → ↓ testosterone.

  • Leuprolide (Lucrin®): 7.5 mg SC/IM monthly or depot q3–6 months.

  • Goserelin (Zoladex®): 3.6 mg SC monthly or 10.8 mg SC q3 months.

  • Triptorelin (Decapeptyl®): 3.75 mg IM monthly or long-acting q3–6 months.
    Flare mitigation: short course Bicalutamide (Casodex®) 50 mg orally once daily.

GnRH antagonists — immediate LH suppression (no flare).

  • Degarelix (Firmagon®): 240 mg SC loading, then 80 mg SC every 4 weeks.

  • Relugolix (Orgovyx®): 120 mg orally once daily.

Androgen receptor antagonists (next gen) — inhibit AR nuclear translocation/DNA binding.

  • Enzalutamide (Xtandi®): 160 mg orally once daily.

  • Apalutamide (Erleada®): 240 mg orally once daily.

  • Darolutamide (Nubeqa®): 600 mg orally twice daily with food.
    Watch: fatigue, hypertension; interactions via CYP enzymes (less with darolutamide).

CYP17A1 inhibitor — blocks androgen synthesis (adrenal & intratumoral).

  • Abiraterone acetate (Zytiga®): 1000 mg orally once daily on an empty stomach, plus Prednisone 5 mg orally twice daily.
    Monitor: BP, potassium, liver function; mineralocorticoid excess is the classic toxicity.

Monitoring targets:

  • Prostate: testosterone < 50 ng/dL (castrate level), PSA kinetics, alkaline phosphatase.

  • Breast: ER/PR documented; CA 15-3/CEA (adjuncts only), imaging by RECIST v1.1.

Resistance (what flips the switch):

  • ESR1 mutations (AI resistance) → consider SERD.

  • AR-V7 splice variant → poor response to AR antagonists.

  • Pathway bypass (PI3K/AKT/mTOR, MAPK) or intratumoral steroidogenesis.

(Anchors: NCCN 2025; ESMO 2024; ASCO 2023–2024)