HRT Increases Risk of Benign Breast Disease

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Researchers at the Albert Einstein College of Medicine in New York City have discovered that women who took a common form of estrogen as hormone replacement therapy (HRT) during menopause more than doubled their risk for certain types of benign breast disease—for example, benign proliferative breast disease—as compared with women who took a placebo—over an average follow-up of almost seven years. Benign proliferative breast disease is relatively common and has also been linked with an increased risk of breast cancer.

The clinical implication for women contemplating the use of supplemental estrogen “doesn’t really change,” said study author Dr. Tom Rohan, chairman of the department of epidemiology and population health at the Albert Einstein College of Medicine in New York City. “It’s the idea that women need to balance the benefits and risks,” he said. This new finding does point to an added risk, however, Rohan added. Rohan’s team published the study online on April 8 in the Journal of the National Cancer Institute.

Until now, there have been no randomized studies—considered the gold standard of scientific testing—on the effect of conjugated equine estrogen (CEE), a type of HRT, and its link to the risk of developing benign proliferative breast disease. This data is generated from the huge Women’s Health Initiative (WHI) CEE trial, in which almost 11,000 postmenopausal women were randomly assigned to receive CEE or a placebo.

Experts believe invasive breast cancer can result from a succession of conditions, with benign proliferative breast disease without atypia (cell abnormalities) sometimes followed by proliferative disease with atypia before development of in situ (localized) cancer. This study did not see an increase in the risk of developing invasive breast cancer but the progression from benign proliferative breast disease to invasive breast cancer could take a decade and this study was not long enough to note that change. The progress of the women in the trial is still being followed, the researchers noted.

The WHI also found women taking estrogen with progestin experienced increased risk of breast cancer and benign proliferative breast disease after about five years of follow-up, suggesting progestin may be linked to breast cancer development. “This makes perfect sense,” said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. “Estrogen does stimulate breast tissue activity and my concern is that, if you do move along a continuum as the hypothesis states, as you stimulate the breast are you going to be able to predict which women are going to develop into something worse and women who are going to stay in a benign state. I can’t predict which of those women will develop [breast cancer] down the line but we know that this agent is highly stimulatory to breast tissue so the question is, do you want to be taking an agent that stimulates breast tissue?”

Last month, also as a follow-up to the up to the WHI, research revealed that while heart problems linked with combination HRT in postmenopausal women decreases when hormones are stopped, the breast cancer risk increases after women stop HRT.

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