# Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test

Source: https://onco.cc/roadmaps/hormonal-therapy-roadmap/  
OnCo record `hormonal-therapy-roadmap` (Roadmap). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cutting off the hormones that breast and prostate cancers feed on has kept people alive for decades. The therapy is now moving from blocking the hormone to destroying its receptor, and from waiting for a scan to switching drugs when a blood test sees resistance coming.

## Summary

Endocrine therapy is the oldest targeted treatment in oncology: removal of the ovaries for breast cancer in 1896 and castration for prostate cancer in 1941 predate every drug. Tamoxifen (1977) made it a pill, aromatase inhibitors and GnRH analogues refined it, and for two decades the field advanced by combination: CDK4/6 inhibitors with endocrine therapy in breast cancer, and abiraterone, enzalutamide and docetaxel layered onto androgen deprivation in prostate cancer, each adding survival in randomised trials.

The current generation attacks resistance directly. Oral oestrogen-receptor degraders (elacestrant 2023, imlunestrant 2025, camizestrant 2026) and the first approved PROTAC (vepdegestrant 2026) remove the receptor rather than block it and work in tumours with ESR1 mutations; SERENA-6 was the first trial to change treatment on a blood test rather than a scan. PI3K, AKT and mTOR inhibitors address the parallel escape route. In prostate cancer, PARP inhibitors and AKT inhibitors are being matched to the tumours whose biology predicts benefit, and PSMA radioligands are moving earlier.

The pace is set by resistance biology, by the cost of multi-year combination therapy, and by tolerability: the side-effects that make people stop a drug they should take for five or ten years.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-10

## Sources

- SERENA-6 (NEJM 2025): https://www.nejm.org/doi/full/10.1056/NEJMoa2502929
- STAMPEDE platform trial: https://www.stampedetrial.org/

## Connected records

- ideas: [Cardiometabolic screening and treatment for survivors on long-term hormone therapy](https://onco.cc/ideas/idea-acc-cardiometabolic-clinic-hormone-therapy/), [ctDNA-guided dose holidays for lung cancer targeted therapy](https://onco.cc/ideas/idea-bio1-ctdna-adaptive-tki/), [Fund trials that test shorter courses of the most expensive adjuvant drugs](https://onco.cc/ideas/idea-cost-shorter-course-trials/), [Low-dose tamoxifen for high-risk women, prescribed by pharmacists and nurses](https://onco.cc/ideas/idea-prev-low-dose-tamoxifen-uptake/), [Reduce the dose once the cancer responds: response-adapted de-escalation trials](https://onco.cc/ideas/idea-tr1-response-adapted-dose-reduction/)
- roadmaps: [Paths to cures: interception, eradication, control](https://onco.cc/roadmaps/cure-paths/), [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/), [Radiopharmaceutical roadmap: iodine → lutetium → actinium](https://onco.cc/roadmaps/radiopharma-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- cancers: [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Hormonal Therapy](https://onco.cc/fronts/hormonal/)
- technologies: [Acupuncture for aromatase-inhibitor joint pain](https://onco.cc/technologies/acupuncture-aromatase-inhibitor-arthralgia/), [Acupuncture for hot flushes on endocrine therapy](https://onco.cc/technologies/acupuncture-hot-flushes/), [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Cardio-oncology](https://onco.cc/technologies/cardio-oncology/), [CDK4/6 inhibitors](https://onco.cc/technologies/cdk46-inhibitor/), [Endocrine therapy (SERMs, AIs, SERDs)](https://onco.cc/technologies/endocrine-therapy/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/)
- drugs: [Abemaciclib](https://onco.cc/drugs/abemaciclib/), [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Alpelisib](https://onco.cc/drugs/alpelisib/), [Apalutamide](https://onco.cc/drugs/apalutamide/), [Atirmociclib](https://onco.cc/drugs/atirmociclib/), [Bicalutamide](https://onco.cc/drugs/bicalutamide/), [Breast Cancer Index](https://onco.cc/drugs/breast-cancer-index/), [Camizestrant](https://onco.cc/drugs/camizestrant/), [Capivasertib](https://onco.cc/drugs/capivasertib/), [Dalpiciclib](https://onco.cc/drugs/dalpiciclib/), [Darolutamide](https://onco.cc/drugs/darolutamide/), [Degarelix](https://onco.cc/drugs/degarelix/), [Elacestrant](https://onco.cc/drugs/elacestrant/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Everolimus](https://onco.cc/drugs/everolimus/), [Exemestane](https://onco.cc/drugs/exemestane/), [Fluoroestradiol F-18 (FES PET)](https://onco.cc/drugs/fluoroestradiol-f18/), [Fulvestrant](https://onco.cc/drugs/fulvestrant/), [Gedatolisib](https://onco.cc/drugs/gedatolisib/), [Giredestrant](https://onco.cc/drugs/giredestrant/), [Goserelin / leuprolide (ovarian function suppression)](https://onco.cc/drugs/goserelin/), [Imlunestrant](https://onco.cc/drugs/imlunestrant/), [Inavolisib](https://onco.cc/drugs/inavolisib/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/), [Leuprolide (leuprorelin) and GnRH agonists](https://onco.cc/drugs/leuprolide/), [Mevrometostat](https://onco.cc/drugs/mevrometostat/), [Palbociclib](https://onco.cc/drugs/palbociclib/), [Relugolix](https://onco.cc/drugs/relugolix/), [Ribociclib](https://onco.cc/drugs/ribociclib/), [Tamoxifen](https://onco.cc/drugs/tamoxifen/), [Vepdegestrant](https://onco.cc/drugs/vepdegestrant/)
- trials: [ARASENS](https://onco.cc/trials/arasens/), [ARCHES](https://onco.cc/trials/arches/), [CAMBRIA-1 & CAMBRIA-2](https://onco.cc/trials/cambria/), [CAPItello-281](https://onco.cc/trials/capitello-281/), [CAPItello-291](https://onco.cc/trials/capitello-291/), [CHAARTED (E3805)](https://onco.cc/trials/chaarted/), [EMBARK](https://onco.cc/trials/embark/), [EMBER-3](https://onco.cc/trials/ember-3/), [EMERALD](https://onco.cc/trials/emerald/), [evERA](https://onco.cc/trials/evera/), [FOURLIGHT-1](https://onco.cc/trials/fourlight-1/), [LATITUDE](https://onco.cc/trials/latitude/), [lidERA](https://onco.cc/trials/lidera/), [MAGNITUDE](https://onco.cc/trials/magnitude/), [MEVPRO-1](https://onco.cc/trials/mevpro-1/), [MONALEESA-2](https://onco.cc/trials/monaleesa-2/), [MONARCH 3](https://onco.cc/trials/monarch-3/), [monarchE](https://onco.cc/trials/monarche/), [NATALEE](https://onco.cc/trials/natalee/), [PALLAS & PENELOPE-B](https://onco.cc/trials/pallas-penelope-b/), [PALOMA-2](https://onco.cc/trials/paloma-2/), [PEACE-1](https://onco.cc/trials/peace-1/), [persevERA](https://onco.cc/trials/persevera/), [postMONARCH](https://onco.cc/trials/postmonarch/), [PROpel](https://onco.cc/trials/propel/), [PSMAfore](https://onco.cc/trials/psmafore/), [SERENA-6](https://onco.cc/trials/serena-6/), [SOFT & TEXT](https://onco.cc/trials/soft-text/), [SOLAR-1](https://onco.cc/trials/solar-1/), [STAMPEDE](https://onco.cc/trials/stampede/), [TALAPRO-2](https://onco.cc/trials/talapro-2/), [VERITAC-2](https://onco.cc/trials/veritac-2/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [Huggins and Hodges 1941: the effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate](https://onco.cc/key-papers/paper-huggins-hodges-castration-serum-phosphatases-prostate-1941/)

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