According to research published in the Archives of Internal Medicine, new-onset breast tenderness during conjugated equine estrogens plus medroxyprogesterone therapy was associated with increased breast cancer risk.

Researchers evaluated data from the Women's Health Initiative Estrogen + Progestin Trial, which randomised post-menopausal women with an intact uterus to receive daily conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg (n = 8506), or placebo (n = 8102). At baseline and annually, participants underwent mammography and clinical breast examination. Self-reported breast tenderness was assessed at baseline and at 12 months, and the incidence of invasive breast cancer was confirmed by medical record review (mean follow-up of 5.6 years).

The following results were reported:
• Of the women without baseline breast tenderness (n = 14,538), statistically significantly more assigned to receive conjugated equine estrogens plus medroxyprogesterone vs. placebo experienced new-onset breast tenderness after 12 months (36.1% vs. 11.8%, P < 0.001).
• Of women in the conjugated equine estrogens plus medroxyprogesterone group, breast cancer risk was significantly higher in those with new-onset breast tenderness compared with those without (hazard ratio, 1.48; 95% confidence interval, 1.08-2.03; P = 0.02).
• In the placebo group, breast cancer risk was not associated with new-onset breast tenderness (P = 0.97).

The researchers also concluded that new-onset breast tenderness during conjugated equine estrogens plus medroxyprogesterone therapy may be a marker of increased breast cancer risk, and raises the possibility that reports of breast tenderness during conjugated equine estrogens plus medroxyprogesterone therapy may identify high-risk women.