Hormonal Agents in Cancer Therapy

Introduction & principles

• Principle — the growth of breast and prostate carcinoma is hormone-dependent; interrupting steroid-hormone signalling delays recurrence and prolongs survival. Hormonal agents are not cytotoxic — they are cytostatic/palliative and must be given for prolonged periods (e.g. tamoxifen ≥5 years).
• Three strategies — (1) inhibit hormone production — GnRH analogues, aromatase inhibitors, abiraterone; (2) block hormone–receptor binding — SERMs, AR antagonists; (3) degrade the receptor — SERDs (fulvestrant).
• Receptors — ER, PR, AR and GR are ligand-activated nuclear-receptor transcription factors; blocking their activation silences gene networks driving tumour growth.
• Historical — breast cancer was the first neoplasm shown to respond to hormonal manipulation; Huggins (1941) showed androgens drive prostate cancer, establishing androgen-deprivation therapy (ADT) — Nobel Prize 1966.
• Predictive biomarker — ER+/PR+ breast tumours have a >60% chance of responding to endocrine therapy; ER–/PR– tumours do not respond. Response is lower when ER+ tumours are also HER2-amplified.