The risk that women using hormone replacement therapy (HRT) will develop breast cancer depends on the formulation and duration of use, a new analysis suggests.

Researchers matched 98,611 breast cancer patients in the UK aged 50-79 years with 457,498 controls. Overall, 34 per cent of women with breast cancer and 31 per cent of controls had used HRT prior to one year before the index date.

The authors excluded the year before the index date to reduce the risk of bias from undiagnosed breast cancer. They defined ‘recent’ as more than one year and less than five years before the index date and longterm use as at least five years.

Compared with women who had never taken HRT, those who recently used long-term oestrogen-only therapy were 15 per cent more likely to develop breast cancer. The risk was 77 per cent higher among women who recently used long-term combined oestrogen and progestogen therapy. For combined progestogens, the increased risk was greatest for norethisterone (88 per cent higher) and lowest for dydrogesterone (24 per cent).

Previous studies suggest that cancer risks decline after women stop taking HRT, but remain elevated for several years. In this analysis, past long-term use of oestrogen-only HRT and past short-term use of oestrogenprogestogen were not associated with an increased risk of breast cancer. The risk was 16 per cent higher with past long-term use of oestrogen-progestogen HRT.

The authors estimate that:

• Recent oestrogen-only use is associated with between three and eight extra cases per 10,000 women years depending on age and treatment duration
• Recent oestrogen-progestogen use is associated with between nine and 36 extra cases per 10,000 women years
• Past oestrogen-progestogen use is associated with between two and eight extra cases per 10,000 women years.

“This large observational study found that exposure to most HRT drugs is associated with an increased risk of breast cancer,” the authors conclude.

“Risk increases were mostly associated with oestrogenprogestogen treatments, but small increases were also associated with oestrogen-only treatments”.