Starting hormone therapy at around the time of menopause is associated with a greater risk of breast cancer compared to starting after a longer gap, according to a study published online Jan. 28 in The Journal of the National Cancer Institute. In this large, prospectively followed cohort of women, those who started hormone therapy five years or more after menopause had little or no increased risk, regardless of the type of hormone therapy used, how long they used it, and whether they were overweight or obese.

Many studies have established that breast cancer incidence increases in users of hormonal therapy, in particular among women who use an estrogen-progestin combination as opposed to estrogen-alone. Few studies have looked at the timing of hormone therapy as a risk factor, although two previous studies suggested the interval between menopause and initiating hormone therapy may influence breast cancer risk.

To investigate this question, Valerie Beral, FRS, of Oxford University and colleagues, used data from the Million Women Study (MWS) in the UK. The researchers estimated the adjusted relative risks of breast cancer in hormone therapy users and past users compared to non-users in 1.13 million women in the study. They also compared women on different types of hormone therapy.

They found that women starting hormone therapy at the time of menopause were at greater risk of breast cancer than those starting it later. They write, "A new finding of this study, which has been little investigated previously, is that the interval between menopause and starting hormonal therapy has a substantial effect on breast cancer risk."

Two previous studies have suggested this association but only in certain subgroups. "In this large study, we found greater risks of breast cancer if hormonal therapy use began either before or soon after menopause than after a longer gap; and this pattern of risk was seen across different types of hormonal therapy, among women who used hormonal therapy for either short of long durations, and also in lean and in overweight and obese women."

In an accompanying editorial, Rowan T. Chlebowski, M.D., Ph.D., of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet Anderson from the Fred Hutchinson Cancer Research Center note the study provides substantial support for similar findings from the Women's Health Initiative (WHI) in the U.S. They add that the similarities between the patterns of breast cancer risk in these two large studies increase the likely validity of the results, especially since the methodologies of the two studies were quite different.

The editorialists also discuss discrepancies in the two studies' findings regarding the risk of estrogen-only hormone therapy; the WHI found little risk associated with estrogen alone while the MWS found a statistically significant increased risk, except in overweight and obese women. They conclude that "the question of the effect of estrogen-only formulation use on breast cancer risk in postmenopausal women, even with longer-term hormone use, still stands unanswered."