This study finds that breast tenderness which develops during estrogen plus progestin hormone replacement therapy (HRT) is associated with increased risk of breast cancer. The study used data from the Women's Health Initiative Estrogen Plus Progestin Trial, which had been halted in 2002 when it was discovered that women in the HRT arm of the trial had a higher incidence of breast cancer. A total of 16,608 postmenopausal women who had not had hysterectomies were randomly assigned to receive either daily conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) or a placebo. Self-reported breast tenderness was recorded at baseline and at the end of one year. The average follow-up period was 5.6-years. Of the 14,538 women who did not have breast tenderness at baseline, 36% in the HRT group compared to 12% in the placebo group experienced new-onset breast tenderness as of the end of one year. Of the 8,506 women in the HRT group, the risk of breast cancer was found to be significantly higher in those with new-onset breast tenderness compared with those without.

Implications for risk of breast cancer

The study findings indicate that women who develop breast tenderness as a result of hormone replacement theory might be more vulnerable to developing breast cancer than those who do not experience such tenderness. The implication is that these women have a higher than average risk among those who use HRT and might benefit from re-evaluating the decision to use it. For those who do continue with HRT, it is important to limit exposure to alcohol and diets with a high glycemic load since both appear to further increase the risk of breast cancer associated with HRT (see studies below).