An update of the outcomes of participants in the Women's Health Initiative has reported that women assigned to the combined hormone replacement therapy (HRT) arm of the study continue to have higher risk of breast cancer and also have higher rates of breast cancer-related death than those assigned to the placebo arm. Combined HRT refers to estrogen plus progestin therapy. It was reported in 2002 that breast cancer incidence was increased by combined HRT in the Women's Health Initiative. The study included 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 U.S. clinical centers. This was a large, randomized, placebo-controlled trial of combined HRT with an average treatment time of 5.6 years and an average follow-up period of 7.9 years. Death resulting from breast cancer among the trial participants has not previously been reported. The present study updates outcomes of the Women's Health Initiative after an average follow-up of period 11.0 years, through August 14, 2009. After the original trial completion date of March 31, 2005, reconsent for continued follow-up for breast cancer incidence was obtained from 12,788 (83%) of the surviving participants.

Combined HRT was found to be associated with 25% higher risk of invasive breast cancer compared with placebo (385 breast cancer cases (0.42% per year) among HRT users compared to 293 cases (0.34% per year) for placebo. Breast cancers in the combined HRT group were similar in histology and grade to tumors in the placebo group but were 78% more likely to be lymph node-positive. There were also almost twice as many breast cancer-related deaths in the combined HRT group compared to the placebo group. In addition, there were 57% more deaths from all causes occurring after a breast cancer diagnosis among the HRT group compared with women in the placebo group. These results appear to contradict other studies which have reported that HRT is associated with hormone receptor positive breast cancer with less aggressive than average characteristics. The authors conclude that estrogen plus progestin is associated with greater breast cancer incidence, and that the cancers are more commonly lymph node positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.