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

The original targeted cancer drug (1977): a pill that blocks oestrogen's effect on breast cancer and halves recurrence, still essential for premenopausal women.

Pills that block or remove oestrogen signalling, the mainstay of treatment for hormone-driven breast cancer for 50 years.

Androgen deprivation lowers testosterone or blocks its receptor, and has been the foundation of prostate cancer treatment since 1941 (Nobel Prize 1966).

Monthly or 3-monthly injections that switch off the ovaries, letting premenopausal women use aromatase inhibitors and lowering recurrence in higher-risk cases.

Leuprolide is the injectable that shuts off testosterone production, the foundation of hormone therapy for prostate cancer since the 1980s; it is also used for ovarian suppression in premenopausal breast cancer.

The old antiandrogen pill used to block the testosterone flare from GnRH agonists and in combined androgen blockade; superseded by enzalutamide-class drugs.

Daily pills that stop the body making oestrogen after menopause, the backbone of hormone therapy for most breast cancers.

Exemestane is a steroidal aromatase inhibitor, the partner of everolimus and the agent tested with ovarian suppression in young women.

Fulvestrant is a monthly injection that destroys the oestrogen receptor; it is the standard partner for many targeted drugs after hormone therapy stops working.

For younger women, shutting down the ovaries and adding an aromatase inhibitor prevents more recurrences than tamoxifen alone, with the largest gains in the highest-risk women.

Hot flushes on tamoxifen or aromatase inhibitors are common and hormone replacement is off the table. Acupuncture reduced flushes in several randomised trials, in one about as well as the drug gabapentin and with fewer side effects, though sham-controlled results are mixed.

Joint pain and stiffness are the main reason women stop aromatase-inhibitor tablets early. In a large randomised trial, twelve weeks of acupuncture reduced that pain more than sham needling or no treatment, and the benefit lasted after the sessions ended.

Abiraterone is a pill that shuts down testosterone production everywhere, including inside the tumour. Discovered at the Institute of Cancer Research, now generic and used from the first metastatic diagnosis.

The most widely used androgen-receptor blocker, approved across every stage of advanced prostate cancer, including rising PSA after surgery.

An AR blocker approved for prostate cancer that has spread and for high-risk disease before it shows on scans.

Darolutamide is an AR blocker that barely enters the brain, so it causes fewer falls and cognitive side effects; it is approved with and without chemotherapy.

Relugolix is the first hormone-suppressing pill for prostate cancer, working within days and wearing off quickly when stopped.

An injectable hormone blocker for prostate cancer that lowers testosterone within days without the initial surge caused by agonists.

The first trial to show chemotherapy at the start of hormone therapy prolongs life in metastatic prostate cancer.

STAMPEDE is the longest-running platform trial in oncology, and showed that both docetaxel and abiraterone extend life when started at first diagnosis of metastatic disease.

LATITUDE established abiraterone at first metastatic diagnosis for high-risk disease.

Brought enzalutamide into first-line metastatic treatment, with an overall survival benefit confirmed in 2021.

Proved 'triplet therapy': adding darolutamide to hormone therapy plus chemotherapy reduces death by a third.

PEACE-1 is the European triplet trial: abiraterone added to hormone therapy and docetaxel improves survival, especially in high-volume disease.

Showed that treating a fast-rising PSA after surgery or radiation with enzalutamide delays spread.

PSMAfore moved Pluvicto before chemotherapy in prostate cancer.

Pills that stop the cell-division engine, added to hormone therapy for the most common type of breast cancer.

Palbociclib was the first CDK4/6 inhibitor (2015), and in 2026 became the first approved as maintenance in HER2-positive, hormone-positive breast cancer.

Ribociclib is the CDK4/6 inhibitor with the most consistent survival benefit, approved for a broad population of early breast cancer patients since 2024.

Abemaciclib was the first CDK4/6 inhibitor approved after surgery for high-risk hormone-positive breast cancer.

Dalpiciclib is Hengrui's CDK4/6 inhibitor, the first China-developed drug of the class, approved for hormone-driven advanced breast cancer on the DAWNA trials.

The trial that made palbociclib the first CDK4/6 inhibitor in routine use. It doubled progression-free time but did not extend life.

The first CDK4/6 inhibitor trial to show that adding the pill to hormone therapy makes women live longer, by about a year.

Abemaciclib roughly doubled the time to progression when added to an aromatase inhibitor; the survival gain of about 13 months narrowly missed statistical significance.

The first CDK4/6 inhibitor to reduce recurrence after surgery in high-risk hormone-positive breast cancer.

Extended CDK4/6 inhibitors to a broad group of early hormone-positive breast cancer patients, including node-negative.

Two large trials found that adding palbociclib after surgery does not prevent recurrence, even though the same drug helps in metastatic disease.

Alpelisib was the first PI3K drug for PIK3CA-mutant breast cancer (2019). It is effective, but high blood sugar and rash limited its use, and newer drugs are displacing it.

The first trial to show a PI3K inhibitor helps in breast cancers carrying a PIK3CA mutation, at the cost of high blood sugar and rash.

Capivasertib (Truqap) is the first AKT inhibitor, for breast cancer with PI3K-pathway mutations and, since 2026, for prostate cancer with PTEN loss.

Adding the AKT inhibitor capivasertib to fulvestrant doubled progression-free time, especially in tumours with PI3K-pathway mutations.

Inavolisib is a PI3K drug that also destroys the mutant protein, approved in 2024 with palbociclib and fulvestrant for PIK3CA-mutant breast cancer.

An intravenous drug that blocks the whole PI3K/mTOR pathway, approved in July 2026 for hormone-positive breast cancer.

An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.

Elacestrant was the first oral oestrogen-receptor degrader (2023), for ESR1-mutant breast cancer detected by blood test.

The first oral oestrogen-receptor degrader to beat standard hormone therapy, with the benefit concentrated in tumours carrying ESR1 mutations.

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.

An oral SERD that works alone in ESR1-mutant tumours and, combined with abemaciclib, doubles progression-free time in everyone regardless of mutation.

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.

The first trial to change treatment because of a blood test rather than a scan: switching to camizestrant when an ESR1 mutation appeared in the blood delayed progression by seven months.

Vepdegestrant is the first PROTAC ever approved (2026): a pill that tags the oestrogen receptor for destruction, for breast cancers with ESR1 mutations.

The trial that got the first PROTAC approved, with benefit only in tumours with ESR1 mutations.

Instead of blocking a protein, these drugs tag it for the cell's own garbage disposal, removing it entirely.

A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour.

A PET scan that shows which breast cancer deposits still have oestrogen receptors, helping decide whether hormone therapy will work when biopsy is impractical.

The first oral SERD to reduce recurrence after surgery, by about 30%, compared with today's hormone pills.

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.

Two very large trials testing whether an oral SERD should replace today's adjuvant hormone pills, either from the start or as a switch.

An oral SERD did not beat the aromatase inhibitor in first-line treatment when both were combined with palbociclib. Oral SERDs earn their place after resistance, not before it.

Continuing CDK4/6 blockade with a different drug after the first one fails gives a small but real benefit.

In evERA, pairing an oral SERD with everolimus after CDK4/6 failure delayed progression by more than three months, and by four and a half months in ESR1-mutant tumours.

A next-generation pill that blocks only CDK4, not CDK6, to keep the benefit of today's drugs without the low blood counts.

In FOURLIGHT-1, a CDK4-only inhibitor designed to avoid the low blood counts of current CDK4/6 drugs improved progression-free survival in second line.

Showed PARP inhibitor plus abiraterone delays progression in first-line mCRPC, with the largest benefit in BRCA-mutant men.

The PARP-plus-hormone combination that eventually showed an overall survival benefit, in 2024-25.

PARP inhibitor plus abiraterone helped men with BRCA mutations and did nothing for those without, settling a debate.

CAPItello-281 delivered the first AKT inhibitor success in prostate cancer, for the ~25% of men whose tumours have lost PTEN.

An epigenetic drug that may re-sensitise prostate cancer to hormone therapy, in three phase 3 trials with enzalutamide.

MEVPRO-1 is the phase 3 trial of the first EZH2 inhibitor combination in prostate cancer.

The only test designed to tell a woman who has finished five years of hormone therapy whether another five years is worth the side effects.

Use tumour DNA in the blood as the signal to pause and restart a lung cancer pill, keeping the tumour in check while slowing the rise of resistant cells.

The dose needed to shrink a tumour may be higher than the dose needed to keep it from growing back. Trials that lower the dose once a response is achieved could reduce long-term side effects without losing control.

Hormone-blocking treatments for prostate and breast cancer, taken for years, raise the risk of diabetes, heart disease and bone fractures. Survivors on these drugs should get the same preventive care as diabetics.

Protecting the heart from cancer treatments, which is increasingly important as patients live longer.

A 5 mg tamoxifen dose halves breast cancer recurrence after precancer with far fewer side effects than the full dose. Almost nobody is prescribed it. Change who can prescribe.

Nearly every targeted therapy stops working within months to a few years as the tumour adapts.

New cancer drugs routinely cost over $150,000 a year, often for months of benefit. Systems cannot afford them and patients go bankrupt.

The PERSEPHONE trial showed six months of trastuzumab after surgery is as good as twelve, halving the drug cost; no company will run such trials, so public funders and charities must.

Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.

Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.