Extended use of unopposed estrogen linked to breast cancer

By Fran Lowry

NEW YORK (Reuters Health) – Long-term use of unopposed estrogen therapy – defined as more than 10 years – is linked to a higher risk of breast cancer, researchers reported April 1st in Chicago at the American Association for Cancer Research (AACR) annual meeting.

“This was something that we expected to find,” lead author Dr. Wendy Y. Chen, from Brigham and Women’s Hospital and the Dana-Farber Cancer Institute in Boston told Reuters Health.

“It’s already been shown that patients shouldn’t be undergoing estrogen plus progesterone hormone therapy long term, and now we show that people should also be careful about longer-term use of estrogen-alone hormone therapy,” she said.

The risk was linear, Dr. Chen added, rising the longer the women were on estrogen therapy.

“In previous studies, researchers only evaluated risks that were associated with less than 10 years of hormone therapy use. We wanted to look at the effects with longer use,” she said.

Dr. Chen and her team evaluated data from the Nurses’ Health Study, which followed 121,700 female registered nurses from 1980 through 2008 who were aged 30 to 55 years in 1976. The women filled out questionnaires about their medication use, risk factors and cancer incidence every two years.

Only postmenopausal women were included in this analysis.

The researchers found that the risk for breast cancer was 88% higher in women who had taken estrogen plus progesterone for 10 to 14.9 years compared with women who did not use estrogen plus progesterone (relative risk 1.88). This risk more the doubled for women who used estrogen plus progesterone therapy for 15 to 19.9 years (RR 2.35).

For women who used estrogen only, the researchers found a 22% increased risk for breast cancer if used for 10 to 14.9 years (RR 1.22) and a 43% increased risk for 15 to 19.9 years of use (RR 1.43), compared with women who did not use unopposed estrogen.

To further clarify long-term risks of estrogen-only therapy, Dr. Chen and her colleagues evaluated a subset of the women who also met the criteria for participation in the Women’s Health Initiative randomized trial of postmenopausal women aged 50 years or older.

They found that the risk for breast cancer was reduced slightly for women who used estrogen alone for less than 10 years, (RR 0.93) compared with non-users. The risk increased 30% for women who took estrogen for 15 to 19.9 years (RR 1.30).

Although breast cancer incidence was increased among women who used estrogen-progesterone or estrogen alone, there was no increase in fatal breast cancer, Dr. Chen reported.

Commenting on this study for Reuters Health, Dr. Jo Freudenheim, from the University of Buffalo, New York, noted that observational studies such as Dr. Chen’s have limitations.

“There is always the possibility of confounding in a variety of ways,” she said. “How often did the women get a mammogram? How often did they go to the doctor? What was their access to health care? Did they have health insurance? Did they exercise? What was their diet like? All these things might be correlated with whether they take hormones.”

“There are a lot of unanswered questions here,” she added. “Using unopposed estrogen for 15 to 20 years is a lot longer than many women use it for and it could be that this group of women are different in some way.”