# IBIS-I: five years of tamoxifen keeps preventing breast cancer for at least 20 years

Source: https://onco.cc/key-papers/paper-ibis-i-tamoxifen-lancet-oncol-2015/  
OnCo record `paper-ibis-i-tamoxifen-lancet-oncol-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In women at increased risk, 5 years of tamoxifen reduced breast cancer by 29% over a median 16 years of follow-up, with the benefit continuing long after the pills stopped, but no reduction in breast cancer deaths.

## Summary

IBIS-I randomised 7,154 women aged 35-70 at increased risk of breast cancer to tamoxifen 20 mg daily or placebo for 5 years. This long-term analysis had a median follow-up of 16 years.

Breast cancer (invasive plus ductal carcinoma in situ) occurred in 251 tamoxifen-arm and 350 placebo-arm women (HR 0.71). The reduction was similar in the first 10 years and after 10 years, showing a carry-over effect. Oestrogen-receptor-positive invasive cancer fell by a third; ER-negative cancer was unaffected. There was no difference in breast cancer mortality. Endometrial cancer and thromboembolic events were increased mainly during active treatment.

With the earlier NSABP P-1 trial (49% reduction at 5 years), IBIS-I is the basis for guideline recommendations of tamoxifen for risk reduction.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Lancet Oncology
- Year: 2015
- DOI: 10.1016/S1470-2045(14)71171-4
- Authors: Cuzick J, Sestak I, Cawthorn S, et al.
- Findings: Breast cancer HR 0.71 (95% CI 0.60-0.83) over median 16 years; 251 vs 350 cases; ER-positive invasive breast cancer HR 0.66; no effect on ER-negative disease; Benefit continued beyond 10 years after randomisation (HR 0.69 for years 10 and later); No significant difference in breast cancer deaths (31 vs 26) or all-cause mortality; Endometrial cancer was increased during the 5 treatment years but not afterwards
- What it means: For women at raised risk, a 5-year course of tamoxifen offers long-lasting protection against the commonest kind of breast cancer. Uptake is low because of side effects and fear of rare serious harms; low-dose tamoxifen (TAM-01) is now being tested to improve the balance. It has not been shown to save lives.
- Caveats: No mortality benefit despite fewer cancers, partly because ER-positive cancers are highly treatable; Only about 10% of eligible women in most countries accept preventive tamoxifen; Increased endometrial cancer and venous thromboembolism during treatment, concentrated in postmenopausal women; Risk assessment relied on family history criteria of the 1990s rather than modern risk models

## Sources

- DOI: https://doi.org/10.1016/S1470-2045(14)71171-4
- NSABP P-1 (Fisher 1998): https://doi.org/10.1093/jnci/90.18.1371

## Connected records

- ideas: [Low-dose tamoxifen for high-risk women, prescribed by pharmacists and nurses](https://onco.cc/ideas/idea-prev-low-dose-tamoxifen-uptake/), [One master trial for cancer prevention drugs across many precancers](https://onco.cc/ideas/idea-prev-chemoprevention-master-protocol/)
- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- fronts: [Hormonal Therapy](https://onco.cc/fronts/hormonal/), [Prevention & Risk](https://onco.cc/fronts/prevention/)
- technologies: [Chemoprevention & risk-reducing surgery](https://onco.cc/technologies/chemoprevention/), [Endocrine therapy (SERMs, AIs, SERDs)](https://onco.cc/technologies/endocrine-therapy/)
- targets: [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)
- drugs: [Tamoxifen](https://onco.cc/drugs/tamoxifen/)
- bottlenecks: [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/), [Prevention we already have is not deployed](https://onco.cc/bottlenecks/b-prevention-adoption/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)
- people: [Jack Cuzick](https://onco.cc/people/jack-cuzick/)

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