This page shows what was measured, who it was measured in, and what that does not settle.
What Tamoxifen does in the body
Tamoxifen sits in the same dock and does not switch those genes on, so the growth signal stops.
Most breast cancers grow because oestrogen docks into a receptor inside the cell and switches on the genes that make it divide. The complication is that the same receptor exists in other tissues and the drug does not behave the same way everywhere: in the lining of the uterus it acts like oestrogen rather than against it, which is why it raises the risk of uterine cancer, and in bone it also acts like oestrogen, which is why it protects against fractures. One molecule, one receptor, opposite effects depending on which tissue it is in.
Why people take it. Used to treat or prevent breast cancer that grows in response to oestrogen.
What happened in people
Five years of treatment roughly halved early recurrence and cut breast-cancer deaths by about one third.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
For healthy high-risk women, studies show fewer cancers, not fewer breast-cancer deaths.
Where it acts
The oestrogen receptor in breast epithelium — and the same receptor in the uterine lining, where the drug does the opposite thing
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
12 registered substances share the start of this name, which is why a search for it can return more than one thing.
FDA substance registry · 1ZE05C816A · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
A reviewer approved this sentence against this exact record and its sources.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 142 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Healthy ageing
…Waiting for a reviewer1 registered study measure of this kind. No reviewed result yet.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Healthy ageing
all cause mortality
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
… Waiting for a reviewer
1 registered study measure of this kind. No reviewed result yet.
∅ Nothing in the sources checked
No registered study lists a performance measure for this goal.
— Not recorded
Harms were not a registered measure for this goal.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Breast cancer recurrence and breast cancer mortality with about 5 years of adjuvant tamoxifen against none, by oestrogen receptor status
✓ The study showed what it set out to show
Who was studied
EBCTCG patient-level meta-analysis of 20 adjuvant tamoxifen trials (Lancet 2011;378:771-784)
How many people
21457
Study design
Collaborative meta-analysis of individual patient data from randomised trials
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Recurrence RR 0.53 (SE 0.03) years 0-4 and 0.68 (0.06) years 5-9 in ER-positive disease (both 2p<0.00001); breast cancer mortality RR 0.71, 0.66 and 0.68 across years 0-4, 5-9 and 10-14 (p<0.0001 for each period)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Small absolute increases in thromboembolic and uterine cancer mortality, both confined to women older than 55. Recurrence RR during years 10-14 was 0.97 (0.10), indicating the recurrence benefit of a five-year course neither grows nor reverses after year 10. Compliance was about 80%.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 10 and 20 mg of tamoxifen citrate, and an oral solution (Soltamox) for people who cannot swallow tablets — taken once or twice daily for five to ten years
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
Breast cancer recurrence and mortality with tamoxifen continued to 10 years against stopping at 5 years, in oestrogen receptor-positive disease
✓ The study showed what it set out to show
Who was studied
ATLAS (Davies C et al., Lancet 2013;381:805-816; ISRCTN19652633)
How many people
12894
Study design
Randomised, open control, extended-duration trial
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Recurrence 617 of 3,428 against 711 of 3,418 (p=0.002); breast cancer mortality 331 against 397 deaths (p=0.01); overall mortality 639 against 722 (p=0.01)
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Endometrial cancer rate ratio 1.74 (95% CI 1.30 to 2.34, p=0.0002), with cumulative risk during years 5-14 of 3.1% against 1.6% and mortality 0.4% against 0.2%. Pulmonary embolus rate ratio 1.87 (1.13 to 3.07, p=0.01). Ischaemic heart disease went the other way at 0.76 (0.60 to 0.95, p=0.02). Almost all the extra breast cancer benefit appeared after year 10.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 10 and 20 mg of tamoxifen citrate, and an oral solution (Soltamox) for people who cannot swallow tablets — taken once or twice daily for five to ten years
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
251 of 3,579 (7.0%) against 350 of 3,575 (9.8%) after a median 16 years; hazard ratio 0.71 (95% CI 0.60 to 0.83), p<0.0001
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The primary endpoint is incidence, not mortality. No effect was seen on invasive oestrogen receptor-negative breast cancer (HR 1.05, 95% CI 0.71 to 1.57). The harms quantified in the boxed warning — endometrial cancer, stroke and pulmonary embolism — come from the sister prevention trial NSABP P-1.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 10 and 20 mg of tamoxifen citrate, and an oral solution (Soltamox) for people who cannot swallow tablets — taken once or twice daily for five to ten years
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
Association of CYP2D6 metaboliser phenotype with breast cancer-free interval or distant recurrence in tamoxifen-treated patients
✗ The study did not show it
Who was studied
CYP2D6 pharmacogenomic analyses within BIG 1-98 and ATAC (J Natl Cancer Inst 2012;104:441-451 and 452-460)
How many people
5596
Study design
Prospectively collected genotype analyses within two randomised phase 3 trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
BIG 1-98: no association in tamoxifen monotherapy without prior chemotherapy (p=0.35); poor or intermediate against extensive metaboliser HR 0.86 (95% CI 0.60 to 1.24). ATAC: poor against extensive metaboliser HR for distant recurrence 1.25 (0.55 to 3.15, p=0.64) and any recurrence 0.99 (0.48 to 2.08, p=0.99)
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. In BIG 1-98 the reduced-activity phenotypes had more tamoxifen-induced hot flushes (p=0.020), the opposite of what the metabolic hypothesis predicted, which removed the proposed use of hot flushes as a marker of adequate activation.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 10 and 20 mg of tamoxifen citrate, and an oral solution (Soltamox) for people who cannot swallow tablets — taken once or twice daily for five to ten years
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
■Living longer, or avoiding a major eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.11 registered measures of this kind. No reviewed result.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.3 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.1 registered measure inside human tissue.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse, Dog. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Tamoxifen
What a person takes: Oral tablet at 10 and 20 mg of tamoxifen citrate, and an oral solution (Soltamox) for people who cannot swallow tablets — taken once or twice daily for five to ten years.
The measurement behind this step
A single 20 mg dose gives a mean peak plasma concentration of 40 ng/mL at about 5 hours, declining biphasically with a terminal half-life of 5 to 7 days. Steady state takes about 4 weeks for tamoxifen and 8 weeks for its major metabolite N-desmethyltamoxifen. A 20 mg tablet once daily is bioequivalent to 10 mg twice daily, and the oral solution is bioequivalent to tablets and unaffected by food. Metabolism runs through CYP3A, CYP2D6, CYP2C9, CYP2C19 and CYP2B6, and the two most potent metabolites, endoxifen and 4-hydroxytamoxifen, have 100-fold greater receptor affinity than the parent.
Getting in
A tablet that takes a month to reach full effect
Tamoxifen stays in the body for a long time — the half-life is measured in days, and its main metabolite in weeks. Steady levels take about a month to build up.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
After a single 20 mg dose, mean peak plasma concentration is 40 ng/mL at about 5 hours, with biphasic decline and a terminal half-life of 5 to 7 days. Steady state is reached in about 4 weeks for tamoxifen and about 8 weeks for N-desmethyltamoxifen, implying a half-life near 14 days for the metabolite. Food does not affect absorption of the oral solution.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
The tablet is largely a precursor. Liver enzymes convert a small fraction of it into two metabolites that are a hundred times better at gripping the receptor.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Extensive metabolism by CYP3A, CYP2D6, CYP2C9, CYP2C19 and CYP2B6. N-desmethyltamoxifen, formed predominantly by CYP3A, is the major plasma metabolite with activity similar to the parent. The label states endoxifen and 4-hydroxytamoxifen, identified as minor metabolites, have 100-fold greater oestrogen receptor affinity, with steady-state concentrations of 29.1 and 3.7 ng/mL.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
Inside the cell, the drug takes the place oestrogen would occupy on the receptor and does not switch on the growth genes.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label describes tamoxifen as an oestrogen agonist/antagonist that competes with oestrogen for binding to the oestrogen receptor, which can result in decreased oestrogen-receptor-signalling-dependent growth in breast tissue. The bound receptor still dimerises and reaches DNA; what changes is which coregulator proteins it recruits.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
Endometrium expresses a different set of helper proteins, so the same drug-receptor complex switches genes on there instead of off. That is where the uterine cancer risk comes from.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Tissue selectivity arises from the relative abundance of coactivators such as SRC-1 and corepressors such as NCoR. The consequence is quantified in the boxed warning: endometrial adenocarcinoma at 2.20 against 0.71 per 1,000 women-years and uterine sarcoma at 0.17 against 0.04 in NSABP P-1. Bone is the third tissue, where agonism is protective — tamoxifen was associated with lower nonvertebral fracture risk (RR 0.66, 95% CI 0.45 to 0.98) in the USPSTF review.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
Across twenty trials and more than twenty thousand women, five years of the drug roughly halved recurrence early on and cut breast cancer deaths by about a third for fifteen years.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Recurrence rate ratio 0.53 (SE 0.03) during years 0-4 and 0.68 (0.06) during years 5-9 in oestrogen receptor-positive disease. Breast cancer mortality rate ratio 0.71, 0.66 and 0.68 across three successive five-year periods, p<0.0001 for extra mortality reduction in each. Little or no effect in receptor-negative disease.
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
The benefit outlasts the drug — and so does the calculation
Stopping after five years does not end the protection; the mortality benefit continues for at least a decade. Continuing to ten years adds more, but mostly after year ten.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
In the meta-analysis, recurrence rate ratio during years 10-14 was 0.97 (0.10) — neither further gain nor loss after year 10 for a five-year course — while breast cancer mortality reduction persisted through years 10-14. In ATLAS, continuing to ten years gave a recurrence rate ratio of 0.90 (0.79 to 1.02) during years 5-9 and 0.75 (0.62 to 0.90) later, with breast cancer mortality 0.97 (0.79 to 1.18) then 0.71 (0.58 to 0.88).
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
No registered study measured anything of this kind.
Measured
Things only a test, a scale or a device shows.
gene expression
bone mineral density of the lumbar spine
hemoglobin level
bone mineral density
Meaningful
Things that change how a life goes, not only a number.
disease free survival
overall survival
event free survival
all cause mortality
relapse free survival
progression free survival
evaluation of the disease free survival
time to disease progression
5 year disease free survival
disease free survival in premenopausal
and 1 more.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (25)
endometrial pathologic diagnosis
pathological response
adverse events
overall clinical response rate
complementary deoxyribonucleic acid expression
duration of dfs
positive axillary lymph nodes
pathologic complete response rate in the breast and axilla
daily hot flushes at 3 months from baseline
hot flush at 3 months from baseline
comparison of time to progression
time to progression
free from breast cancer
failure free at 2 years following study entry
local tumor control
safety and tolerability
scores on cars m scale at trial completion
objective tumour response
ipsilateral breast tumor recurrence
6 month tumor volume compared to baseline using mammography
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. about 5 to 7 days
Read from the label, which states: “The decline in plasma concentrations of tamoxifen is biphasic with a terminal elimination half-life of about 5 to 7 days.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Women and men with oestrogen receptor-positive breast cancer, women with ductal carcinoma in situ after surgery and radiation, and women at high risk who choose prevention. It does essentially nothing in oestrogen receptor-negative disease, and the meta-analysis says so.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of SOLTAMOX in pediatric patients have not been established.”
US prescribing information · 1e6ff055-590c-41e6-9530-1fdf04cdbd02 · read 2026-08-30
On older people, the label states: “Ductal Carcinoma in Situ In the NSABP B-24 trial, the percentage of women at least 65 years of age was 23%.”
US prescribing information · 1e6ff055-590c-41e6-9530-1fdf04cdbd02 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary SOLTAMOX can cause fetal harm when administered to a pregnant woman .”
US prescribing information · 1e6ff055-590c-41e6-9530-1fdf04cdbd02 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of tamoxifen or its metabolites in human milk or its effects on the breastfed infant.”
US prescribing information · 1e6ff055-590c-41e6-9530-1fdf04cdbd02 · read 2026-08-30
Where the result stopped carrying
CYP2D6-guided tamoxifen dosing, proposed on a correct mechanism, was not supported by either of the two large randomised-trial genotype analyses
Hot flushes as a marker of adequate metabolic activation failed in the opposite direction — reduced-activity phenotypes had more of them
The uterine cancer and pulmonary embolism signals were large enough to put four numeric incidence rates into the boxed warning
Extending treatment from five to ten years produced no significant breast cancer mortality benefit during years 5-9 (RR 0.97) and delivered almost all of it after year 10
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet at 10 and 20 mg of tamoxifen citrate, and an oral solution (Soltamox) for people who cannot swallow tablets — taken once or twice daily for five to ten years
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S3, S6.
No source is stored against this line.
What is in the pack
A single 20 mg dose gives a mean peak plasma concentration of 40 ng/mL at about 5 hours, declining biphasically with a terminal half-life of 5 to 7 days. Steady state takes about 4 weeks for tamoxifen and 8 weeks for its major metabolite N-desmethyltamoxifen. A 20 mg tablet once daily is bioequivalent to 10 mg twice daily, and the oral solution is bioequivalent to tablets and unaffected by food. Metabolism runs through CYP3A, CYP2D6, CYP2C9, CYP2C19 and CYP2B6, and the two most potent metabolites, endoxifen and 4-hydroxytamoxifen, have 100-fold greater receptor affinity than the parent.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Boxed warning for uterine malignancies, stroke and pulmonary embolism, with fatal cases of each, and with incidence rates per 1,000 women-years quoted from NSABP P-1: endometrial adenocarcinoma 2.20 against 0.71, uterine sarcoma 0.17 against 0.04, stroke 1.43 against 1.00, pulmonary embolism 0.75 against 0.25. The warning directs discussing benefits against these risks with women at high risk and women with ductal carcinoma in situ considering the drug for risk reduction, and states that for most patients already diagnosed with breast cancer the benefits outweigh the risks. Cataracts occur more often than on placebo. Concurrent tamoxifen is an independent risk factor for hydroxychloroquine retinopathy (odds ratio 4.59). Hot flushes are the commonest reason for stopping.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
SOLTAMOX (tamoxifen citrate) United States prescribing information — boxed warning, Indications 1.1 to 1.4, Warnings and Precautions 5.1 and 5.2, Mechanism o… · a recorded source, not a stored snapshot
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Tamoxifen appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 699 reaction mentions were counted. One report can name several reactions.
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet at 10 and 20 mg of tamoxifen citrate, and an oral solution (Soltamox) for people who cannot swallow tablets — taken once or twice daily for five to ten years
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Steady state takes about 4 weeks for tamoxifen and 8 weeks for its major metabolite N-desmethyltamoxifen. A 20 mg tablet once daily is bioequivalent to 10 mg twice daily, and the oral solution is bioequivalent to tablets and unaffected by food. Metabolism runs through CYP3A, CYP2D6, CYP2C9, CYP2C19 and CYP2B6, and the two most potent metabolites, endoxifen and 4-hydroxytamoxifen, have 100-fold greater receptor affinity than the parent.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
29 products list this as an active ingredient in the United States drug directory. 29 of them contain it and nothing else.
FDA National Drug Code directory · 75907-058 · read 2026-08-29
They are sold as liquid, powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 75907-058 · read 2026-08-29
The regulator's established pharmacologic class for it is estrogen agonist/antagonist [epc] and selective estrogen receptor modulators [moa].
FDA National Drug Code directory · 75907-058 · read 2026-08-29
14 published labels name it as an active ingredient. 14 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · c6c6a643-57d6-7ea5-7da0-e8a66802468a · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · c6c6a643-57d6-7ea5-7da0-e8a66802468a · read 2026-08-29
Soltamox is oral solution at Each 10 mL of solution contains 20 mg tamoxifen, equivalent to 30.4 mg tamoxifen citrate, recorded as prescription product; fda label in effect 2021-11-29 in the United States.
US prescribing information · 1e6ff055-590c-41e6-9530-1fdf04cdbd02 · read 2026-08-28
Recorded price in US: 0.13316–0.28326 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 13 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Tamoxifen studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That preventing breast cancers in high-risk women prevents deaths from breast cancer — the prevention indication is licensed on incidence and no mortality reduction has been shown
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That CYP2D6 genotype predicts who benefits, which two analyses in over 5,500 randomised patients did not support
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a relative risk reduction of a third describes any individual woman’s benefit, when the proportional effect is constant and the absolute benefit tracks her baseline risk
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the drug is worth taking in oestrogen receptor-negative disease, where the meta-analysis found little or no effect on recurrence or mortality
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Tamoxifen are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
A third off breast cancer mortality, sustained for fifteen years
In plain words
Individual data from 21,457 women in twenty randomised trials show that five years of tamoxifen roughly halves recurrence in the first five years and cuts death from breast cancer by about a third — and the benefit is still there ten and fifteen years later, long after the drug has stopped.
What was measured
Recurrence and breast cancer mortality rate ratios by five-year period across 15 years, in 21,457 women
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A collaborative patient-level meta-analysis of 20 trials of about five years of adjuvant tamoxifen against none, with about 80% compliance. In oestrogen receptor-positive disease (n=10,645), recurrence rate ratios were 0.53 (SE 0.03) during years 0-4 and 0.68 (0.06) during years 5-9, both 2p<0.00001, and 0.97 (0.10) during years 10-14, indicating neither further gain nor loss after year 10. Breast cancer mortality was reduced by about a third throughout fifteen years: RR 0.71 (0.05) years 0-4, 0.66 (0.05) years 5-9, and 0.68 (0.08) years 10-14, with p<0.0001 for extra mortality reduction in each separate period. The proportional reduction was approximately independent of progesterone receptor status, age, nodal status and chemotherapy use. Non-breast-cancer mortality was little affected despite small absolute increases in thromboembolic and uterine cancer mortality — both only in women over 55 — so all-cause mortality was substantially reduced. In oestrogen receptor-negative disease, tamoxifen had little or no effect on recurrence or mortality. Even marginally positive tumours at 10 to 19 fmol/mg cytosol protein showed a substantial reduction (RR 0.67, 0.08). Receptor status was the only recorded factor importantly predictive of proportional benefit.
Written into the record, not signed off as a reviewed claim
The prevention indication is licensed on incidence, not on deaths
In plain words
For a woman who already has breast cancer, tamoxifen prevents deaths — that is measured. For a healthy woman at high risk, what has been shown is fewer cancers, not fewer deaths from them.
What was measured
That reducing breast cancer incidence in high-risk women reduces breast cancer deaths — the endpoint the prevention indication is licensed on is incidence, and no mortality reduction has been demonstrated in that setting
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 1.4 of the label reads: "to reduce the incidence of breast cancer in adult women at high risk for breast cancer" — an incidence endpoint, stated as such. IBIS-I randomised 7,154 women at increased risk to tamoxifen 20 mg daily or placebo for five years; after a median 16 years, 251 of 3,579 (7.0%) developed breast cancer against 350 of 3,575 (9.8%), hazard ratio 0.71 (95% CI 0.60 to 0.83, p<0.0001), with protection persisting after treatment stopped (HR 0.69, 0.53 to 0.91 beyond year 10). The reduction was concentrated in oestrogen receptor-positive invasive disease (HR 0.66, 0.54 to 0.81) with no effect on receptor-negative disease (HR 1.05, 0.71 to 1.57). The 2019 USPSTF evidence review pooled four placebo-controlled prevention trials in 28,421 women, finding tamoxifen associated with lower incidence of invasive breast cancer (RR 0.69, 95% CI 0.59 to 0.84) alongside higher endometrial cancer, cataracts and thromboembolic events — and reports no mortality reduction among its outcomes. The USPSTF recommendation is a B, offered specifically to women at increased risk who are at low risk of adverse medication effects, with a recommendation against routine use in women not at increased risk. Preventing a cancer is a real benefit. It is not the same measurement as preventing a death from one, and the prevention literature has only made the first.
Written into the record, not signed off as a reviewed claim
CYP2D6 genotyping was going to personalise it, and then it was not
In plain words
Tamoxifen has to be converted by a liver enzyme into its potent form, so it seemed obvious that people with a slow version of that enzyme would do worse. Two analyses inside large randomised trials, in over 5,500 women, found no such thing — and one found the slow metabolisers doing marginally better.
What was measured
Breast cancer-free interval and distant recurrence by CYP2D6 metaboliser phenotype in two randomised trial populations
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The hypothesis was mechanistically compelling: CYP2D6 converts tamoxifen to endoxifen, which the label states has 100-fold greater oestrogen receptor affinity than the parent, so poor metabolisers should get less drug effect. Two genotyping analyses embedded in randomised trials tested it. In BIG 1-98, tumour DNA from 4,861 of 8,010 postmenopausal women was genotyped at nine CYP2D6 polymorphisms; among patients on tamoxifen monotherapy without previous chemotherapy there was no association between metaboliser phenotype and breast cancer-free interval (p=0.35), and poor or intermediate metabolisers had a non-significantly reduced risk of recurrence against extensive metabolisers (HR 0.86, 95% CI 0.60 to 1.24) — the opposite direction from the prediction. Reduced-activity phenotypes were, however, associated with more tamoxifen-induced hot flushes (p=0.020), also contrary to the hypothesis. In ATAC, 1,203 patients were genotyped for CYP2D6 and 1,209 for UGT2B7; after a median ten years there was no significant association between CYP2D6 genotype and recurrence in tamoxifen-treated patients (poor against extensive metaboliser, HR for distant recurrence 1.25, 95% CI 0.55 to 3.15, p=0.64; any recurrence 0.99, 0.48 to 2.08, p=0.99), and a near-null association for UGT2B7. Both papers state the results do not support using CYP2D6 genotype to predict benefit. The episode is worth recording precisely because the mechanism was correct — endoxifen really is the potent species — and the clinical inference from it was not.
Written into the record, not signed off as a reviewed claim
Uterine cancer and pulmonary embolism, with numbers in the boxed warning
In plain words
The boxed warning does not hedge. In the prevention trial, endometrial cancer occurred at 2.20 per thousand women-years on tamoxifen against 0.71 on placebo, and pulmonary embolism at 0.75 against 0.25. Fatal cases of each occurred.
What was measured
Incidence per 1,000 women-years of endometrial adenocarcinoma, uterine sarcoma, stroke and pulmonary embolism against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The boxed warning gives incidence rates per 1,000 women-years from the NSABP P-1 prevention trial: endometrial adenocarcinoma 2.20 against 0.71; uterine sarcoma 0.17 against 0.04; stroke 1.43 against 1.00; pulmonary embolism 0.75 against 0.25 — and states that fatal cases of each type have occurred. It then draws the distinction that the whole risk-benefit argument turns on: discuss the benefits against these risks with women at high risk and women with DCIS considering the drug to reduce risk, and "for most patients already diagnosed with breast cancer, the benefits of tamoxifen outweigh its risks." Two different populations, the same drug, the same harm rates, and a different answer. The ATLAS extended-duration trial quantifies what a further five years costs: cumulative endometrial cancer risk during years 5-14 of 3.1% with continued tamoxifen against 1.6% for controls, with mortality of 0.4% against 0.2% — an absolute mortality increase of 0.2 percentage points, set against an absolute breast cancer mortality reduction of 2.8 percentage points in the same window.
Written into the record, not signed off as a reviewed claim
Ten years beat five, and most of the extra benefit arrived after year ten
In plain words
Doubling the course from five years to ten reduced recurrences and deaths further — but almost all of the extra benefit appeared after the tenth year, which is a decade after the decision to continue has to be made.
What was measured
Recurrence, breast cancer mortality and overall mortality with 10 years against 5 years of adjuvant tamoxifen
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ATLAS randomised 12,894 women who had completed five years of tamoxifen to continue to ten years or stop, reporting breast cancer outcomes in the 6,846 with oestrogen receptor-positive disease. Continuing reduced recurrence (617 in 3,428 against 711 in 3,418, p=0.002), breast cancer mortality (331 against 397 deaths, p=0.01) and overall mortality (639 against 722, p=0.01). The timing matters: recurrence rate ratio was 0.90 (95% CI 0.79 to 1.02) during years 5-9 and 0.75 (0.62 to 0.90) afterwards; breast cancer mortality rate ratio was 0.97 (0.79 to 1.18) during years 5-9 and 0.71 (0.58 to 0.88) afterwards. Cumulative recurrence during years 5-14 was 21.4% against 25.1%, and breast cancer mortality 12.2% against 15.0%, an absolute reduction of 2.8 percentage points. There was no effect in the 1,248 women with receptor-negative disease and an intermediate effect in the 4,800 with unknown status. Non-breast-cancer mortality without recurrence was little affected (RR 0.99, 0.89 to 1.10). The carried-forward harm is pulmonary embolus (RR 1.87, 1.13 to 3.07) and endometrial cancer (RR 1.74, 1.30 to 2.34); ischaemic heart disease went the other way (RR 0.76, 0.60 to 0.95).
Written into the record, not signed off as a reviewed claim
It does essentially nothing without the receptor, and the meta-analysis says so
In plain words
In tumours without the oestrogen receptor, tamoxifen had little or no effect on recurrence or on death. Receptor status was the only patient factor that predicted whether the drug worked.
What was measured
That a relative risk reduction reported from a meta-analysis describes the benefit an individual woman can expect — the proportional reduction is constant, so the absolute benefit varies with her baseline risk while the absolute harm rates do not
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The 2011 patient-level meta-analysis states that in oestrogen receptor-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality, and that receptor status was the only recorded factor importantly predictive of the proportional reductions — not progesterone receptor status or level, not age, not nodal status, not whether chemotherapy had been given. The practical consequence the authors draw is often skipped: because the proportional reduction is constant across those groups, the absolute benefit depends entirely on the absolute risk without tamoxifen. The same relative risk reduction of a third produces a large absolute benefit in a woman with high recurrence risk and a small one in a woman with low risk, and it is the absolute number that has to be weighed against a boxed warning with fixed absolute harm rates. That is the arithmetic behind the label’s statement that the answer differs between women already diagnosed and women considering prevention.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A competitive oestrogen receptor antagonist in breast and agonist in uterus, which in pooled individual data from 21,457 women cut breast cancer recurrence by about half in the first five years and breast cancer mortality by about a third across fifteen — while its own boxed warning records endometrial adenocarcinoma at 2.20 against 0.71 per 1,000 women-years and pulmonary embolism at 0.75 against 0.25 in the prevention trial.
Recorded evidence blocks (15)
Q2
What did Tamoxifen's largest trial (20000 people) and its longest (30 years) measure?
20000 people in Tamoxifen's largest registered study, 30 years in its longest registered window, measuring Changes in Senescence and Secondary Biomarkers, Including TMEM, Mena, and 67LR. ClinicalTrials.gov · 2026-09-01
149 phase2, 122 phase3, 32 phase1, 22 na or unstated, 17 phase4, 16 na, 4 early phase1; NCT06982313; 2026-03-08. Last human test completed 2026, NCT05150652.
Interpretation These counts include studies where Tamoxifen was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase2
149
phase3
122
phase1
32
na or unstated
22
phase4
17
na
16
2 more recorded rows
early phase1
4
Last recorded human testNCT05150652
2026-06-10
recorded 2026-09-01 · last checked 2026-09-04
Q3
From mouse to human: where has Tamoxifen shown lifespan?
Did Tamoxifen move epigenetic clock, and by how much?
epigenetic clock: "We studied mice with cardiomyocyte-specific, tamoxifen-activated loss of PKP2 (cardiomyocyte-specific conditional knockout of plakophilin-2) using conventional and multiplex imaging, cytokine arrays, epigenetic clocks, spatial transcriptomics, expansion and structured illumination microscopy, and correlative data…" Europe PMC · epigenetic clock search · 2026-04-28
2 recorded sentences; 2026, 2025; biomarker
Show the evidence
epigenetic clock
PMID 42047205
2026; "We studied mice with cardiomyocyte-specific, tamoxifen-activated loss of PKP2 (cardiomyocyte-specific conditional knockout of plakophilin-2) using conventional and multiplex imaging, cytokine arrays, epigenetic clocks, spatial transcriptomics, expansion and structured illumination microscopy, and correlative data analysis."
2025; "We studied mice with cardiomyocyte-specific, tamoxifen-activated loss of PKP2 (PKP2cKO) using conventional and multiplex imaging, cytokine arrays, epigenetic clocks, spatial transcriptomics, expansion and structured illumination microscopy, and correlative data analysis."
recorded 2026-04-28 · last checked 2026-09-04
Q7
Tamoxifen's half-life is about 5 to 7 days — which schedules were studied?
about 5 to 7 days, the half-life Tamoxifen's label states. openfda-label · 509f8ba3-214d-aec8-e063-6294a90af498 · 2026-08-28
Show the evidence
half life
about 5 to 7 days; The decline in plasma concentrations of tamoxifen is biphasic with a terminal elimination half-life of about 5 to 7 days.
metabolism
Metabolism: Tamoxifen is extensively metabolized after oral administration.
recorded 2026-08-28 · last checked 2026-09-04
Q8
Which of 5 year disease free survival, 6 month tumor volume compared to baseline using mammography and adverse events did Tamoxifen's trials measure?
5 year disease free survival, 6 month tumor volume compared to baseline using mammography and adverse events lead 40 outcome terms across Tamoxifen's trials. ClinicalTrials.gov · 2026-09-01
Interpretation endometrial pathologic diagnosis, all cause mortality, pathological response, adverse events, overall clinical response rate and complementary deoxyribonucleic acid expression follow.
Show the evidence
disease free survival
1
overall survival
1
event free survival
1
endometrial pathologic diagnosis
1
all cause mortality
1
pathological response
1
14 more recorded rows
adverse events
1
overall clinical response rate
1
complementary deoxyribonucleic acid expression
1
duration of dfs
1
positive axillary lymph nodes
1
pathologic complete response rate in the breast and axilla
1
daily hot flushes at 3 months from baseline
1
hot flush at 3 months from baseline
1
relapse free survival
1
progression free survival
1
comparison of time to progression
1
time to progression
1
free from breast cancer
1
evaluation of the disease free survival
1
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which of Tamoxifen's 65 ongoing trials reports first?
5-year Disease-free Survival; Mammographic Breast Density; latest 2037-05-06
Show the evidence
Trial
NCT00310180
"Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)"; n 10273; "5-year Disease-free Survival"; 2030-09-30
NCT01196936
"Low-Dose Tamoxifen Citrate in Reducing Breast Cancer Risk in Radiation-Induced Cancer Survivors"; n 84; "Mammographic Breast Density"; 2028-12-11
NCT01272037
"Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer"; n 5018; "Invasive Disease-Free Survival (IDFS)"; 2027-01-08
NCT01357772
"Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up"; n 500; "Number of invasive breast cancer events and DCIS"; 2028-12-31
NCT01674140
"S1207 Hormone Therapy With or Without Everolimus in Treating Patients With Breast Cancer"; n 1939; "Invasive Disease-Free Survival (IDFS)"; 2030-01
NCT02057133
"A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread"; n 198; "Number of Participants with One or More Drug-Related Adverse Events"; 2026-12
14 further recorded trials
NCT02311933
"Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer"; n 81; "Progression Free Survival (PFS)"; 2027-02-02
NCT02476786
"Endocrine Treatment Alone for Elderly Patients With Estrogen Receptor Positive Operable Breast Cancer and Low Recurrence Score"; n 50; "Response rate"; 2032-07-31
NCT02592083
"Neoadjuvant Response-guided Treatment of Slowly Proliferating Hormone Receptor Positive Tumors"; n 10; "Clinical and Radiological Response"; 2029-02
NCT02603679
"Neoadjuvant Response-guided Treatment of Luminal B-type Tumors and Luminal A-type Tumors With Node Metastases"; n 181; "Radiological Objective Response Rate after Completion of the First 12-week Period of Primary Medical Treatment"; 2031-12-31
NCT02747004
"A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer"; n 234; "Progression Free Survival (PFS)"; 2026-12
NCT02764541
"Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS)"; n 195; "Difference in Anti-proliferative Activity of Patients Given Letrozole Versus Tamoxifen During the Window Phase"; 2031-04
NCT03011684
"Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial"; n 309; "Mature Oocyte Yield"; 2028-03-31
NCT03161353
"Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy."; n 377; "Evaluate the rate of pCR"; 2026-11-01
NCT03621904
"PROMOTE Study: Prediction of Response Of HorMOnal Treatment in Advanced and Recurrent Endometrial Cancer"; n 150; "Response rate"; 2027-09-01
NCT03879577
"Assessing the Response Rate of Neo-adjuvant Taxotere and Trastuzumab in Nigerian Women With Breast Cancer"; n 53; "Number of Participants With Complete Pathologic Response (pCR)"; 2026-09-30
NCT03917082
"Limited Adjuvant Endocrine Therapy for Low Risk Breast Cancer"; n 290; "Distant Relapse Free Interval at five years"; 2029-05-01
NCT04174352
"FES Imaging to Optimize Tamoxifen for Metastatic Breast Cancer"; n 12; "Rate of FES Blockade at each dose level to determine the Optimal Tamoxifen Dose"; 2027-12
NCT04569747
"A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer"; n 393; "Invasive Disease Free Survival at 3 Years"; 2030-09-01
NCT04666961
"Impact of Neoadjuvant Hormonal Therapy on the Surgical Management of Extensive Ductal Carcinomas in Situ"; n 262; "Efficacy of neoadjuvant hormonotherapy"; 2033-08-01
recorded 2026-09-01 · last checked 2026-09-04
Q10
Which running trial of Tamoxifen could settle lifespan?
NCT05890287 measures Progression-free survival, reading out 2026-10-01.
20 open trials; n 60; "A Study of Chidamide Plus Endocrine in Maintenance Treatment of HR+/HER2- Breast Cancer After First-line Chemotherapy"
Show the evidence
Trial
NCT05890287
"A Study of Chidamide Plus Endocrine in Maintenance Treatment of HR+/HER2- Breast Cancer After First-line Chemotherapy"; n 60; "Progression-free survival"; 2026-10-01
NCT05306340
"A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer)"; n 373; "Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population"; 2026-10-15
NCT02747004
"A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer"; n 234; "Progression Free Survival (PFS)"; 2026-12
NCT01272037
"Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer"; n 5018; "Invasive Disease-Free Survival (IDFS)"; 2027-01-08
NCT02311933
"Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer"; n 81; "Progression Free Survival (PFS)"; 2027-02-02
NCT04765098
"Tamoxifen Versus Etoposide After First Recurrence in GBM Patients"; n 60; "3 month progression-free survival"; 2027-07
14 further recorded trials
NCT06979596
"A Study of MK-5684 in People With Certain Solid Tumors (MK-5684-015/OMAHA-015)"; n 250; "Progression-Free Survival (PFS) - All Cohorts"; 2027-11-04
NCT06914674
"Tamoxifen for Advanced Solid Pseudopapillary Tumor of the Pancreas"; n 30; "Progression-free survival (PFSn)"; 2028-02-28
NCT06355401
"Maintenance Hormonal Therapy and DLBCL"; n 100; "disease free survival"; 2029-03
NCT05826964
"Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer"; n 24; "Progression-Free Survival 1 (PFS1) Among Participants in Step 2"; 2029-07-31
NCT01674140
"S1207 Hormone Therapy With or Without Everolimus in Treating Patients With Breast Cancer"; n 1939; "Invasive Disease-Free Survival (IDFS)"; 2030-01
NCT04569747
"A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer"; n 393; "Invasive Disease Free Survival at 3 Years"; 2030-09-01
NCT00310180
"Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)"; n 10273; "5-year Disease-free Survival"; 2030-09-30
NCT05891093
"Efficacy and Safety of Fluzoparib Combined With Adjuvant Endocrine Therapy for HR+/HER2- SNF3-subtype Early Breast Cancer (BCTOP-L-A01)"; n 766; "invasive disease free survival (iDFS)"; 2031-05-31
NCT05514054
"A Study of Imlunestrant Versus Standard Endocrine Therapy in Participants With Early Breast Cancer"; n 8000; "Invasive Disease-Free Survival (IDFS)"; 2032-03
NCT06492616
"A Study of Elacestrant Versus Standard Endocrine Therapy in Women and Men With ER+,HER2-, Early Breast Cancer With High Risk of Recurrence"; n 4220; "Invasive Breast Cancer-Free Survival (IBCFS)"; 2032-10
NCT06223698
"Optimizing Extended Adjuvant Endocrine Therapy in Patients With Breast Cancer"; n 3832; "Overall survival"; 2035-05-02
NCT05512364
"Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse (TREAT ctDNA)"; n 220; "Distant metastasis free survival (DMFS)"; 2035-11-01
NCT05774951
"A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy"; n 4300; "Invasive breast cancer-free survival (IBCFS)"; 2036-05-29
NCT05952557
"An Adjuvant Endocrine-based Therapy Study of Camizestrant (AZD9833) in ER+/HER2- Early Breast Cancer (CAMBRIA-2)"; n 5511; "Invasive breast cancer-free survival (IBCFS)"; 2037-05-06
Q11
Which 105 trials of Tamoxifen posted no result?
Posted no result
105 of 105 completed trials
Registrations
NCT00000529, NCT00784862, NCT00002755, NCT00003050, NCT00309491 and NCT00001436, and 99 more
Completion dates
oldest 1995-11; newest 2024-03-04
Show the evidence
Trial
NCT00000529
1995-11
NCT00784862
1999-03
NCT00002755
1999-06
NCT00003050
2000-03
NCT00309491
2000-03
NCT00001436
2000-09
14 further recorded trials
NCT00002680
2000-12
NCT00003080
2001-05
NCT00003035
2001-06
NCT00002679
2002-01
NCT00005886
2002-08
NCT00003099
2003-01
NCT00003972
2003-03
NCT00005822
2003-10
NCT00784680
2004-04
NCT00309478
2004-06
NCT00287534
2004-09
NCT00214110
2005-01
NCT00002608
2005-04
NCT00253539
2005-04
Q12
At the median, Tamoxifen's trials enrolled 106.5 people — anything larger?
Median enrolment
106.5
Largest enrolment
20000
Registered trials counted
332
Q13
What do 699 spontaneous reports say about Tamoxifen — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Tamoxifen appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 699 reaction mentions were counted: malignant neoplasm progression 134; disease progression 85; metastases to bone 83; breast cancer metastatic 72. open-targets-adr · CHEMBL786 · 2026-06-24
Show the evidence
malignant neoplasm progression
134
disease progression
85
metastases to bone
83
breast cancer metastatic
72
uterine polyp
71
neoplasm progression
59
4 more recorded rows
pulmonary embolism
56
endometrial hyperplasia
53
hot flush
45
breast cancer
41
recorded 2026-06-24 · last checked 2026-09-04
Q14
Tamoxifen and CYP2D6, CYP2B6 and CYP2C19: shared by which compounds?
CYP2D6, CYP2B6 and CYP2C19 appear in Tamoxifen's recorded interaction sentences, 12 in all. openfda-label+europepmc · 2026-08-30
Metabolism Tamoxifen is extensively metabolized by CYP450 enzymes, including CYP3A, CYP2D6, CYP2C9, CYP2C19, and CYP2B6.
CYP2C19pharmacokinetics
Metabolism Tamoxifen is extensively metabolized by CYP450 enzymes, including CYP3A, CYP2D6, CYP2C9, CYP2C19, and CYP2B6.
CYP2C9pharmacokinetics
Metabolism Tamoxifen is extensively metabolized by CYP450 enzymes, including CYP3A, CYP2D6, CYP2C9, CYP2C19, and CYP2B6.
CYP2D6
pharmacokinetics
Metabolism Tamoxifen is extensively metabolized by CYP450 enzymes, including CYP3A, CYP2D6, CYP2C9, CYP2C19, and CYP2B6.
pharmacokinetics
The polymorphic enzyme CYP2D6 is involved in the formation of endoxifen and 4-hydroxytamoxifen, and it is the key enzyme that catalyzes the formation of endoxifen from N-desmethyltamoxifen.
pharmacokinetics
Endoxifen concentrations may differ among patients because of various CYP2D6 genotypes [see Clinical Pharmacology (12.5) ] .
pharmacokinetics
CYP2D6 Inhibitors Although concomitant administration of CYP2D6 inhibitors reduces the plasma concentration of endoxifen, a potent metabolite, the clinical significance is not well established [see Drug Interactions (7.4) ] .
pharmacokinetics
The mean steady-state endoxifen plasma concentration in patients taking CYP2D6 inhibitors was significantly reduced compared to those not taking concomitant CYP2D6 inhibitors (14.8 ± 10.6 versus 26.7 ± 15.4 ng/mL).
pharmacokinetics
The mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors was 31.4 ± 14.7 ng/mL compared to 8.8 ± 3.5 ng/mL in CYP2D6 normal metabolizers receiving potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) with tamoxifen.
3 more recorded rows
CYP2D6pharmacokinetics
The plasma levels of endoxifen in CYP2D6 normal metabolizers taking potent CYP2D6 inhibitors were similar to the levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors (8.8 versus 7.2 ng/mL) .
CYP2D6clinical_pharmacology
Medroxyprogesterone Medroxyprogesterone reduces the plasma concentration of N-desmethyl tamoxifen, but not that of tamoxifen. 12.5 Pharmacogenomics The impact of CYP2D6 polymorphisms on the efficacy of tamoxifen is not well established.
CYP2D6clinical_pharmacology
CYP2D6 poor metabolizers carrying two non-functional alleles exhibit significantly lower endoxifen plasma concentrations compared to patients carrying one or more fully functional alleles of CYP2D6.
recorded 2026-08-30 · last checked 2026-09-04
Q15
Was Tamoxifen studied with fasting and exercise?
fasting and exercise are named in Tamoxifen's label sentences: "In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass…" openfda-label+europepmc · 2026-08-30
2 recorded statements; fasting, exercise
Show the evidence
fasting
In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass index (BMI), blood pressure (BP), total cholesterol (TC), fasting glucose, and the NLR.
exercise
Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate,…
recorded 2026-08-30 · last checked 2026-09-04
Q16
What is recorded about Tamoxifen and mTOR?
"The aim of this study is to investigate the mechanistic role of estrogen receptor (ER)-mediated mTOR hyperactivation in promoting meningioma progression and to evaluate the therapeutic potential of targeting this signaling axis with tamoxifen." — where Tamoxifen and mTOR appear together. Europe PMC · pathway abstract search · 2026-07-07
"The aim of this study is to investigate the mechanistic role of estrogen receptor (ER)-mediated mTOR hyperactivation in promoting meningioma progression and to evaluate the therapeutic potential of targeting this signaling axis with tamoxifen."
PMID 41348684
"Nano-curcumin treatment significantly inhibits cell proliferation, viability, and migration and promotes apoptosis in tamoxifen-sensitive and resistant MCF7 cell lines. qRT-PCR and Western blot analyses revealed reduced expression of Cyclin D1, DILA1, NF-κB, PI3K, AKT, mTOR, VEGFα, MMP2, and BCL2, along with increased levels of PTEN, TIMP3, RECK, and BAX."
autophagyPMID 38874683
"Interestingly, tamoxifen modulates the nutrition deprivation-induced endoplasmic reticulum stress through enhancing the selective ER-phagy, a specialized autophagy."
AMPK
PMID 38874683
"The tamoxifen-induced ER-phagy is mediated by AMPK activation."
PMID 38874683
"The pharmacological inhibition of AMPK blocks tamoxifen-induced ER-phagy and tamoxifen modulatory effect on ER stress during nutrition deprivation."
PMID 38874683
"Tamoxifen modulates ER stress by inducing ER-phagy through AMPK, thereby, may support breast cancer cell survival during nutrition deprivation conditions."
mTORPMID 39819881
"This study investigates rapamycin, an mTOR inhibitor, as a potential novel strategy for preventing tamoxifen-induced endometrial proliferation."
autophagy
PMID 40845958
"The Ridaifen (RID) compound series comprises structural analogues of tamoxifen that exhibit more potent anticancer activity and have been implicated in modulating autophagy."
PMID 42411996
"Mechanistically, <b>V-12c</b> degraded both ERα and HDAC6 via the proteasome pathway, induced cell cycle arrest and apoptosis, attenuated hormonal response, disrupted the autophagy-lysosome function, and triggered ferroptosis, collectively contributing to overcoming tamoxifen resistance."
recorded 2026-07-07 · last checked 2026-09-04
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