Researchers affiliated with the Women’s Health Initiative Estrogen + Progesterone Trial have reported that breast tenderness occurring in postmenopausal women after taking hormone replacement therapy (HRT) is associated with an increased risk of developing breast cancer compared with women taking HRT who do not develop breast tenderness. The details of this study appeared in the October 12, 2009 issue of the Archives of Internal Medicine.[1] 

The Women’s Health Initiative Trial randomly allocated 16,608 postmenopausal women between the ages 50-79 with an intact uterus to receive estrogen plus progestin or a placebo. The study was planned for 8.5 years but was terminated after 5.2 years. The primary endpoint of this study was coronary heart disease (CHD), which included nonfatal myocardial infarction and death from CHD. The other adverse endpoints were invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. This study was stopped early because of the higher incidence of invasive breast cancer. The results of this study were published after an average follow-up of five years in 2002 in the Journal of the American Medical Association.

This study indicated that there would be eight excess cases of invasive breast cancer per 10,000 person-years for those taking HRT. An additional seven per 10,000 person-years will have a heart attack, eight will have a stroke, and 18 will have blood clots. There were six fewer colorectal cancers and five fewer hip fractures per 10,000 person-years for those taking HRT. Thus, there were 19 adverse events per 10,000 person-years for those taking HRT. There was no effect of HRT on survival with the 5.2 year follow-up of the study.

In this analysis researchers examined the relationship between new-onset breast tenderness in 14, 538 women participating in the HRT versus placebo trial who did not have breast tenderness at the outset of the study. The incidence of new-onset breast tenderness in women receiving HRT was 36.1% compared with 11.8% in women taking placebo. For patients in the HRT group, those with new-onset breast tenderness had a 48% increased risk of breast cancer compared with those without breast tenderness. In the placebo group, the incidence of breast cancer was not related to new-onset breast tenderness.

Comments: The number of postmenopausal women taking HRT after the initial publication of these data has dropped dramatically. However, women who do take HRT despite these results should be aware that new-onset breast tenderness could be a warning sign for the development of early breast cancer.

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