Hormone-driven cancers (breast, prostate) respond to depriving the target tissue of its growth-hormone signal. Breast: aromatase inhibitors (anastrozole, letrozole, exemestane) block peripheral androgen → estrogen conversion; SERMs (tamoxifen) partial-agonize estrogen receptor with tissue selectivity (antagonist in breast, agonist in endometrium → uterine-cancer signal); SERD (fulvestrant) full-degrades the estrogen receptor; clomiphene is a SERM used for ovulation induction. Prostate: GnRH analogs (leuprolide, triptorelin, goserelin agonists; cetrorelix/ganirelix/degarelix antagonists — covered in END-4) drop testicular T; CYP17 lyase inhibitor (abiraterone) blocks adrenal/intratumoral androgen synthesis; AR antagonists (enzalutamide, bicalutamide) block AR ligand binding. Mifepristone — anti-progesterone with off-label use; covered as PR antagonist.
Organ Systems
endocrine
reproductive
Pathway Steps
androgens → estrogens — via aromatase (CYP19A1) in peripheral adipose + breast tissue; AI target. Aromatase (CYP19A1) converts androgens (testosterone, androstenedione) into estrogens — the sole estrogen source in men and postmenopausal women. Aromatase inhibitors (anastrozole, letrozole) block this to treat ER-positive breast cancer, and the conversion also underlies gynecomastia.
androgens → androgen-receptor-activation — via AR nuclear translocation + AR/DNA binding; bicalutamide/enzalutamide block. Androgens also act directly via the androgen receptor, a nuclear receptor driving male sexual development and prostate growth. This is the target of AR antagonists (enzalutamide) and synthesis blockers (abiraterone) in prostate cancer — the AR axis being its central driver.
Known Modulators
tamoxifen (inhibitor) — ER (SERM, breast-antagonist). SERM; ER+ breast cancer adjuvant 5-10 years; endometrial cancer + VTE signals; CYP2D6 activation (PMs may have reduced efficacy)
fulvestrant (inhibitor) — ER degrader (SERD). IM monthly; ER+ metastatic breast; no agonist activity (unlike SERMs)
anastrozole (inhibitor) — aromatase (CYP19A1). non-steroidal AI; first-line postmenopausal ER+ breast cancer; bone density loss + arthralgias
letrozole (inhibitor) — aromatase (CYP19A1). non-steroidal AI; also off-label for ovulation induction (NEJM 2014 superior to clomiphene in PCOS)
exemestane (inhibitor) — aromatase (CYP19A1, steroidal irreversible). steroidal AI; covalent inactivation of aromatase; mild androgenic side effects
clomiphene (inhibitor) — ER (SERM, hypothalamic-antagonist). SERM; ovulation induction by blocking estrogen feedback at hypothalamus → ↑GnRH/FSH/LH; off-label for male hypogonadism