Estrogen receptor (ERα)
The hormone switch that drives most breast cancers. Blocking or destroying it is the oldest and most effective targeted therapy.
Tamoxifen (SERM), aromatase inhibitors, fulvestrant (SERD), oral SERDs (elacestrant, imlunestrant, camizestrant), and the PROTAC degrader vepdegestrant (approved 2026 for ESR1-mutant disease) form the endocrine armamentarium. ESR1 mutations arise under aromatase-inhibitor pressure and are detected by ctDNA.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · The hormone switch that drives most breast cancers. Blocking or destroying it is the oldest and most effective targeted therapy.
- 1 · What it is
The hormone switch that drives most breast cancers. Blocking or destroying it is the oldest and most effective targeted therapy.
- 2 · What goes wrong in cancer
Ligand-activated nuclear receptor; ESR1 Y537S/D538G mutations render it ligand-independent.
- 3 · How drugs use it
12 products aim at Estrogen receptor (ERα): degraders, hormonal therapies and imaging agents. Drugs cut off the hormone supply, block the receptor so the hormone cannot bind, or send the receptor to the cell's waste disposal.
Biology
Ligand-activated nuclear receptor; ESR1 Y537S/D538G mutations render it ligand-independent.
- HR+ breast cancer (~70% of breast cancers)
- Endometrial
- Ovarian (low-grade serous)
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| HR-positive / HER2-negative breast cancer | 100% | ER+ (>=1% IHC), defining | ~70% of all breast cancers; ESR1 mutation ~30% after AI | Wikipedia |
| Endometrial cancer | 70-80% | ER expression (endometrioid) | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Camizestrant is an oral oestrogen-receptor degrader approved in September 2026 for a new kind of decision: switching treatment when a blood test shows resistance developing, before the cancer visibly grows.
Elacestrant was the first oral oestrogen-receptor degrader (2023), for ESR1-mutant breast cancer detected by blood test.
Exemestane is a steroidal aromatase inhibitor, the partner of everolimus and the agent tested with ovarian suppression in young women.
A PET scan that shows which breast cancer deposits still have oestrogen receptors, helping decide whether hormone therapy will work when biopsy is impractical.
Fulvestrant is a monthly injection that destroys the oestrogen receptor; it is the standard partner for many targeted drugs after hormone therapy stops working.
Giredestrant is Roche's oral SERD: it failed to beat an aromatase inhibitor in first-line metastatic disease but succeeded after surgery and after CDK4/6 failure.
Monthly or 3-monthly injections that switch off the ovaries, letting premenopausal women use aromatase inhibitors and lowering recurrence in higher-risk cases.
Imlunestrant is Lilly's oral oestrogen-receptor degrader, approved in 2025 for ESR1-mutant breast cancer and shown to work with abemaciclib regardless of mutation.
Daily pills that stop the body making oestrogen after menopause, the backbone of hormone therapy for most breast cancers.
Progesterone-like hormones that can reverse early endometrial cancer in women who want to keep their uterus, and control advanced hormone-sensitive disease.
The original targeted cancer drug (1977): a pill that blocks oestrogen's effect on breast cancer and halves recurrence, still essential for premenopausal women.
Vepdegestrant is the first PROTAC ever approved (2026): a pill that tags the oestrogen receptor for destruction, for breast cancers with ESR1 mutations.
Ribociclib is a second adjuvant CDK4/6 option, and the only one with data in node-negative stage II disease. Roughly 3 in 100 patients avoid a relapse or death at three years, so the decision depends heavily on individual risk, tolerance of a three-year oral drug, and cost. Whether the benefit persists after treatment ends, as it did with abemaciclib, needs longer follow-up.
Women with hormone-receptor-positive, HER2-negative breast cancer that has spread to lymph nodes and has other high-risk features can now be offered two years of abemaciclib alongside their hormone therapy, with a durable reduction in relapse. It does not apply to node-negative or low-risk disease, and the diarrhoea and cost are real trade-offs to discuss.
For women at raised risk, a 5-year course of tamoxifen offers long-lasting protection against the commonest kind of breast cancer. Uptake is low because of side effects and fear of rare serious harms; low-dose tamoxifen (TAM-01) is now being tested to improve the balance. It has not been shown to save lives.
Instead of blocking a cancer protein, a drug can now remove it entirely, which works even for proteins without a druggable active site and can overcome resistance driven by target overexpression or mutation. Several degraders are in late-stage trials for breast and prostate cancer.
Latest papers
topQuery for this target: (TITLE:"Estrogen receptor" OR ABSTRACT:"Estrogen receptor" OR TITLE:"ERα" OR ABSTRACT:"ERα" OR TITLE:"ESR1" OR ABSTRACT:"ESR1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Estrogen receptor (ERα), not a curated reading list.
Pages like this
not linked directly; found by shared links- TargetAndrogen receptor
Shares Agonist and antagonist, The first PROTAC: a chimeric molecule that tags a protein for destruction, Receptor, Hormone therapy and the tag hormonal.
- TargetCDK4/6
Shares MONALEESA-2, Matthew P. Goetz, Debu Tripathy, EMBER-3.
- TermAromatase inhibitor
Shares Hormone receptor status (ER / PR), Endocrine resistance, Selective oestrogen receptor degrader (SERD), Letrozole (and other aromatase inhibitors).
- PairingOral SERD + CDK4/6 inhibitor after ESR1 emergence
Shares EMBER-3, Imlunestrant, SERENA-6, Camizestrant.
- ProductRibociclib
Shares MONALEESA-2, Debu Tripathy, Seock-Ah Im, The cell-cycle engine (cyclins & CDKs).
- ProductAbemaciclib
Shares Matthew P. Goetz, EMBER-3, monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer, The cell-cycle engine (cyclins & CDKs).
- TrialSOFT & TEXT
Shares Goserelin / leuprolide (ovarian function suppression), Exemestane, Letrozole (and other aromatase inhibitors), Tamoxifen.
- TechnologyDietitian-led weight-loss programmes in HR-positive breast cancer
Shares Exemestane, Letrozole (and other aromatase inhibitors), Tamoxifen, Lipid synthesis, uptake & cholesterol.