Hormonal Management of Breast Cancer

Introduction & rationale

• Hormone-dependence concept — in a large subset of breast cancers, tumour proliferation and survival are driven by oestrogen signalling through the oestrogen receptor (ER), a ligand-activated transcription factor — these tumours are hormone-dependent and respond to endocrine therapy.
• Three pharmacological strategies — ER+ disease is treated by (i) antagonising oestrogen at the ER (SERMs, SERDs), (ii) reducing oestrogen production (aromatase inhibitors; GnRH/LHRH analogues), and (iii) combining these with cell-cycle or pathway inhibitors (CDK4/6, PI3K, AKT, mTOR).
• Not cytotoxic — hormonal agents are not cytotoxic — they modify the growth of hormone-dependent tumours; they are the sheet-anchor of adjuvant and palliative therapy of carcinoma breast and of primary and secondary breast-cancer prevention.
• Used across the disease continuum — endocrine therapy extends survival and delays or prevents recurrence, and is used in chemoprevention, adjuvant, and metastatic settings.
• Male breast cancer — rare and predominantly (>90%) ER+/PR+; treated by inhibiting the ER with tamoxifen (data on AIs or SERDs in males are scant).