BMJ  2004;328:305 (7 February), doi:10.1136/bmj.328.7435.305-a

News

Another HRT trial is stopped early

London

Another trial of hormone replacement therapy (HRT) has been stopped early by researchers after preliminary findings showed an "unacceptably high risk" of recurrent or new breast cancer associated with the treatment.

The Swedish HABITS (hormonal replacement therapy after breast cancer diagnosis—is it safe?) study was intended to follow 1300 women previously treated successfully for breast cancer. Only 434 women had been randomised when it was stopped on 17 December 2003, two years into its planned five year course. By that stage, 26 participants had developed breast cancer out of 174 women assigned to HRT with at least one follow up. Eight women in the 171 strong control group had a new breast cancer event. Eighty nine women were not included in the analysis. This represented a relative hazard for the treatment group of 3.3 (95% confidence interval 1.5 to 7.4). The study was published this week on the Lancet's website (www.thelancet.com).

The study's lead investigator, Lars Holmberg, from University Hospital, Uppsala, Sweden, said: "The HABITS trial was terminated because women with a history of breast cancer allocated to receive HRT for menopausal symptoms experienced an unacceptably high risk of breast cancer compared with breast cancer survivors allocated to best symptomatic treatment without hormones. Women on active treatment have been advised to discontinue."

The first strong evidence of a link between HRT and breast cancer came in 2002, when the women's health initiative study, an American investigation involving 16 000 women, was stopped three years early after running for five years ( JAMA 2002;288: 321-33[Abstract/Free Full Text]). Preliminary results suggested that taking a combined HRT pill increased the risk of breast cancer, heart attack, and stroke.

That same year the Medical Research Council decided to stop the British WISDOM (women's international study of long duration oestrogen after menopause) trial, arguing that new evidence from other trials made it unlikely that the study would yield fresh insights.

When the HABITS trial was stopped, another Swedish trial, known as the Stockholm study, was also examining HRT and the risk of recurrent breast cancer. The Stockholm researchers had intended to pool their final results with the HABITS trial, but both trials were stopped when the relative hazard to their combined treatment groups was found to have passed a predefined limit of 1.36.

Questions remain, however, over wide disparities in the findings of the two trials. Relative risk of a breast cancer event in the Stockholm HRT treatment group was only 0.82 (95% confidence interval 0.35 to 1.90) when the trial was stopped.

The HABITS study suggested a protective effect of tamoxifen, but not enough of the HABITS participants were taking tamoxifen to allow meaningful analysis. It's unknown how many of the Stockholm participants were taking tamoxifen.

This article has been cited by other articles:

• Stammers, T (2005). As easy as ABC? Primary prevention of sexually transmitted infections. Postgrad. Med. J. 81: 273-275 [Full text]  
• Grant, A. (2004). Stopping clinical trials early. BMJ 329: 525-526 [Full text]  
• Wilson, D. (2004). Partner reduction and the prevention of HIV/AIDS. BMJ 328: 848-849 [Full text]  

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