Core endocrine (hormone‑blocking) treatments

• SERMs – tamoxifen, toremifene, raloxifene
  Target: Bind to the estrogen receptor (ER) and block estrogen signalling in breast cancer cells, acting as ER “antagonists” in breast tissue.pmc.ncbi.nlm.nih+2

• Aromatase inhibitors (AIs) – anastrozole, letrozole, exemestane
  Target: Inhibit the aromatase enzyme that converts androgens to estrogen, dropping circulating estrogen levels (especially in post‑menopausal patients).

• SERD (injectable) – fulvestrant
  Target: Binds to ER and accelerates its degradation, reducing the number of estrogen receptors and shutting down ER signalling.

• Oral SERD – elacestrant (Orserdu)
  Target: Oral selective estrogen receptor degrader that binds and promotes degradation of ER, designed to overcome resistance (especially in ESR1‑mutant ER+/HER2‑ metastatic breast cancer after prior endocrine therapy and CDK4/6).
  Oral SERDs in development – camizestrant, giredestrant, imlunestrant
  Target: Next‑generation oral ER degraders aiming for stronger, more consistent ER blockade and activity in endocrine‑resistant disease, mostly still in phase II–III trials.

• Ovarian function suppression – GnRH agonists (e.g. Goserelin, Zoladex), oophorectomy. Target: Switch off ovarian estrogen production in pre‑menopausal patients, so that ER‑positive tumours lose their main estrogen supply.

Cell‑cycle targeted (usually combined with endocrine therapy)

• CDK4/6 inhibitors – palbociclib, ribociclib, abemaciclib
  Target: Block CDK4 and CDK6, key enzymes that drive cell‑cycle progression from G1 to S phase; this keeps ER‑positive tumour cells “stuck” and unable to divide when ER signalling is also blocked.

Pathway‑targeted add‑ons in endocrine‑resistant disease

• PI3K inhibitor – alpelisib (for PIK3CA‑mutant ER+ disease)
  Target: Inhibits the PI3K‑α subunit, a common growth‑signalling driver in ER+ tumours with PIK3CA mutations, helping restore sensitivity to endocrine therapy.

• mTOR inhibitor – everolimus
  Target: Inhibits mTOR, a central growth and survival pathway downstream of PI3K/AKT, used to overcome endocrine resistance when combined with an AI or fulvestrant.

• AKT inhibitors – newer agents in trials
  Target: Block AKT in the PI3K/AKT/mTOR pathway to reduce survival signalling in ER+ breast cancer, often combined with endocrine therapy in studies.

• HDAC inhibitors – e.g. entinostat (investigational)
  Target: Modify histone deacetylation and gene expression, aiming to re‑sensitise resistant ER+ tumours to hormone therapy.

HER2‑directed for ER+/HER2+ (“luminal B”) disease

• Anti‑HER2 antibodies – trastuzumab, pertuzumab
  Target: Bind HER2 receptors on tumour cells and block HER2 growth signalling; often combined with endocrine therapy in ER+/HER2+ cancers.

• HER2‑targeted TKIs / ADCs – lapatinib, trastuzumab‑emtansine (T‑DM1), others
  Target: Inhibit HER2 tyrosine kinase activity or deliver chemotherapy directly to HER2‑expressing cells, reducing growth and survival of HER2‑positive, ER‑positive tumours.

Chemotherapy (non‑selective cytotoxic)

• Taxanes, anthracyclines, capecitabine, etc.
  Target: Damage dividing cells by disrupting DNA replication or mitotic spindle function; used across subtypes, including ER+, when disease is high‑burden, rapidly progressive, or endocrine‑refractory.

Bone‑targeted (for bone‑predominant metastatic ER+)

• Bisphosphonates – zoledronic acid
  Target: Inhibit osteoclast‑mediated bone resorption, stabilising bone and reducing skeletal‑related events from bone metastases.
• RANKL inhibitor – denosumab
  Target: Binds RANKL to block osteoclast formation and activity, protecting bone in metastatic disease and some high‑risk early‑stage settings.

Immunotherapy (selected ER+ contexts)

• Checkpoint inhibitors – e.g. pembrolizumab in high TMB / PD‑L1+ / MSI‑H tumours
  Target: Block PD‑1/PD‑L1 or CTLA‑4 “brakes” on T‑cells, allowing immune attack; only a subset of ER+ patients currently meet biomarker criteria.