IBIS-II: What the Breast Cancer Trial Found

The question behind the trial

Aromatase inhibitors were already used to stop breast cancer coming back after treatment. IBIS-II asked something different: could one of them stop a first breast cancer from happening at all?

The drug tested was anastrozole. Aromatase is the enzyme that makes estrogen in the tissues of women who have been through menopause, once the ovaries have stopped. Blocking it drives estrogen levels down. Many breast cancers depend on estrogen to grow, so taking it away is a plausible way to prevent them.

How it was built

IBIS-II was an international, double-blind, placebo-controlled randomized trial, registered as ISRCTN31488319.

Between February 2, 2003 and January 31, 2012, it recruited 3,864 postmenopausal women aged 40 to 70 from 18 countries. All were judged to be at increased risk of breast cancer against set criteria. A central computer assigned them 1:1 to 1 mg of oral anastrozole daily or a matching placebo, taken for five years. That was the trial's fixed daily tablet. Prevention prescribing today is decided case by case. Everyone — participants, clinicians, and trial staff — was masked to who got what. Only the trial statistician was not.

That was the trial protocol. Preventive anastrozole is prescribed case by case, so any amount you take should come from your own doctor.

The primary endpoint was histologically confirmed breast cancer, meaning a diagnosis proven on tissue, and it counted both invasive cancers and ductal carcinoma in situ. Analysis was by intention to treat, so women were counted in the group they were assigned to whatever they actually took.

What the five-year report showed

After a median of 5.0 years, 40 women in the anastrozole group had developed breast cancer, against 85 on placebo. That is a hazard ratio of 0.47, with a 95% confidence interval of 0.32 to 0.68. The risk was roughly halved.

The absolute numbers matter as much as the ratio. The predicted cumulative chance of any breast cancer by seven years was 2.8% on anastrozole and 5.6% on placebo. That is about 28 fewer cancers per 1,000 women.

Deaths were close to equal: 18 in the anastrozole group and 17 on placebo, with no cause more common in either arm.

What longer follow-up added

The trial reported again in 2020, after a median of 131 months — nearly 11 years, well past the five years of treatment.

The reduction held and grew in absolute terms: 85 cancers on anastrozole against 165 on placebo, a hazard ratio of 0.51. Splitting by period, the effect was larger during the treatment years, at 0.39, and still present afterwards, at 0.64. The difference between those two figures was not statistically significant, meaning the protection did not clearly fade once the tablets stopped.

Invasive estrogen receptor-positive breast cancer fell by 54%. Ductal carcinoma in situ fell by 59%. That pattern fits the mechanism: a drug that removes estrogen prevents the cancers that need estrogen.

Two other findings are worth recording. Non-breast cancers were less common on anastrozole, 147 against 200, mainly because of non-melanoma skin cancer. And no excess of fractures or cardiovascular disease appeared, which had been a live concern with a drug that lowers estrogen.

Deaths still did not differ: 69 against 70 overall, and two breast cancer deaths against three.

How to read a halved risk

"Risk halved" is true and easy to misread. Halving applies to a starting number, and for most individual women that starting number is small.

Consider the seven-year figures. Out of 1,000 high-risk women on placebo, about 56 developed breast cancer. On anastrozole, about 28 did. So 28 women per 1,000 avoided a cancer over that period, and roughly 944 would not have developed one either way but took a daily tablet for five years regardless.

That is not an argument against the drug. It is the arithmetic anyone deciding about prevention medication needs in front of them, alongside the side effects. Our page on reading cancer statistics and headlines covers the difference between relative and absolute numbers.

When to get checked

This trial is about women already identified as high risk. Getting into that conversation starts with family history and with symptoms.

Ask a clinician about a formal risk assessment if your family includes breast cancer diagnosed before 50, breast and ovarian cancer on the same side, more than one affected relative on one side, or male breast cancer.

And book an appointment now, whatever your risk category, for:

• A new lump in the breast or armpit that lasts past one menstrual cycle
• Dimpling, puckering, or thickening of the skin over the breast
• A nipple that newly turns inward, or scaling that will not clear
• Fluid from one nipple that appears without squeezing, especially if bloody
• A change in the size or outline of one breast only

Our page on breast cancer screening covers what happens next.

What this does not mean

• Only postmenopausal women judged to be at increased risk were studied. The results do not apply to average-risk or premenopausal women.
• The trial showed fewer cancers but no reduction in deaths. With around 139 deaths across both arms at long follow-up, it was never large enough to detect one.
• Anastrozole prevented estrogen receptor-positive disease. It is not expected to prevent cancers that do not depend on estrogen.
• "Increased risk" was defined by the trial's own criteria. Whether an individual meets a comparable threshold is a clinical judgment.
• Prevention medication is a trade, not a free gain. Side effects, five years of daily tablets, and the size of the individual benefit all belong in the same conversation.

Sources

• Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383:1041-8 (PMID 24333009) — https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=pubmed&id=24333009&retmode=xml
• Cuzick J, Sestak I, Forbes JF, et al. Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Lancet. 2020;395:117-122 (PMID 31839281) — https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=pubmed&id=31839281&retmode=xml
• NCI, Breast Cancer—Patient Version — https://www.cancer.gov/types/breast
• NCI PDQ, Breast Cancer Treatment (Health Professional Version) — https://www.cancer.gov/types/breast/hp/breast-treatment-pdq

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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