STAR (P-2): What the Breast Cancer Trial Found

Two prevention drugs, tested against each other

Everyone in STAR was healthy. Nobody had breast cancer. They were taking a daily tablet for five years because their estimated risk was high enough that a drug might be worth it.

Tamoxifen was already approved for reducing that risk, but it had a reputation problem: it raises the risk of uterine cancer and of blood clots. Raloxifene, a drug developed for osteoporosis, had shown a signal against breast cancer in its own trials. STAR asked which of the two was the better bargain.

Who enrolled, and what the risk threshold was

Field	Detail
Trial	STAR (NSABP P-2)
Identifier	NCT00003906
Design	Prospective, double-blind, randomised prevention trial
Participants	19,747 postmenopausal women, mean age 58.5, at nearly 200 centres across North America
Entry criterion	Raised five-year breast cancer risk — mean estimated risk 4.03%
Comparator	Tamoxifen 20 mg a day against raloxifene 60 mg a day, over five years
Primary endpoint	Invasive breast cancer

Those were the study amounts. Neither drug should be started or altered on your own; the decision belongs with your doctor.

Enrolment started on 1 July 1999. The final analysis was set to begin once at least 327 invasive breast cancers had been diagnosed, and the data reported here run to a cutoff of 31 December 2005.

Note what is missing: there is no placebo group. Both arms took an active drug.

On invasive breast cancer, a tie

163 invasive breast cancers occurred among the women assigned tamoxifen and 168 among those assigned raloxifene. The reported incidence was 4.30 per 1,000 against 4.41 per 1,000, a risk ratio of 1.02 (95% CI 0.82 to 1.28).

That interval sits comfortably around 1. On the trial's main question, the two drugs performed the same.

Where the two drugs differed

The interesting results are in the secondary columns.

• Non-invasive breast cancer, such as DCIS: 57 cases on tamoxifen against 80 on raloxifene (1.51 against 2.11 per 1,000; risk ratio 1.40, 95% CI 0.98 to 2.00). Not statistically significant, but pointing against raloxifene.
• Uterine cancer: 36 on tamoxifen against 23 on raloxifene (risk ratio 0.62, 95% CI 0.35 to 1.08). Also not significant at this analysis.
• Blood clots: significantly fewer on raloxifene (risk ratio 0.70, 95% CI 0.54 to 0.91).
• Cataracts: fewer on raloxifene (risk ratio 0.79, 95% CI 0.68 to 0.92), as was cataract surgery (risk ratio 0.82, 95% CI 0.68 to 0.99).
• Osteoporotic fractures: similar in both groups.
• Deaths: 101 on tamoxifen against 96 on raloxifene, with no difference in causes.

Nothing was found for other invasive cancers, heart events or stroke.

What the 2010 update changed

An update published four years later, at a median follow-up of 81 months, revised the headline.

The risk ratio for invasive breast cancer, raloxifene against tamoxifen, was 1.24 (95% CI 1.05 to 1.47). That interval no longer includes 1. On longer follow-up, raloxifene was less effective — the authors put it at retaining about 76% of tamoxifen's effect against invasive disease.

The safety advantages held and in one case sharpened. Endometrial cancer, which had not reached significance in 2006, now favoured raloxifene clearly (risk ratio 0.55, 95% CI 0.36 to 0.83, p=0.003). Uterine hyperplasia strongly favoured raloxifene (0.19, 95% CI 0.12 to 0.29), as did thromboembolic events (0.75, 95% CI 0.60 to 0.93). There were no significant differences in mortality.

So the honest summary is not "equally effective". It is: somewhat less effective, considerably safer, and the trade is a personal one.

What this study cannot tell you

• How much either drug lowers risk compared with taking nothing. There was no placebo arm; that evidence comes from the earlier NSABP P-1 trial.
• Anything about premenopausal women. Everyone here was postmenopausal.
• Anything about treating breast cancer. These women did not have it. Prevention and treatment are different questions.
• What happens outside a trial. Five years of daily tablets in well women is a big ask, and adherence in the real world is not the same as in a study.

Questions about risk-reducing medication

• What is my estimated five-year risk, and how was it calculated?
• Given my own history of clots, cataracts or uterine problems, which drug suits me better?
• What would we do at the end of five years?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• JAMA: Effects of Tamoxifen vs Raloxifene on Risk of Invasive Breast Cancer (STAR P-2) (primary)
• Cancer Prevention Research: Update of the STAR P-2 Trial (primary)

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

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