In a landmark study, researchers have linked the long-term use of estrogen plus progesterone and estrogen-only hormone therapy with a higher risk for developing breast cancer.

"It's already been confirmed that patients shouldn't be undergoing estrogen plus progesterone hormone therapy (HT) for the long term," said Wendy Y. Chen, M.D., M.P.H., associate physician at Brigham and Women's Hospital and assistant professor in medicine at the Breast Cancer Oncology Center at the Dana-Farber Cancer Institute in Boston, Mass. "What we found is that people should also be careful about longer-term use of estrogen-alone HT."

In previous studies, she said, researchers only evaluated risks associated with less than 10 years of HT use. Chen presented the findings at the AACR Annual Meeting 2012, held in Chicago March 31 -- April 4.

Using data from the Nurses' Health Study, the researchers evaluated follow-up data collected during 1980 through 2008 from postmenopausal female registered nurses who were aged 30 to 55 years old in 1976.

Chen and colleagues found that the risk for breast cancer, when compared with women who did not use HT, was 88 percent higher in women who had taken estrogen plus progesterone for 10 to 14.9 years; the risk increased more than twofold for women who used estrogen plus progesterone therapy for 15 to 19.9 years. For women who used estrogen-only HT, researchers found a 22 percent increased risk for breast cancer if used for 10 to 14.9 years and a 43 percent greater risk associated with 15 to 19.9 years of use.

Researchers also found that the risk did not plateau for either kind of HT. "There's a continued effect over time. The longer you use it, the higher the risk," said Chen.

To further clarify long-term risks of estrogen-only therapy, the researchers evaluated a subset of the women who also met the requirements of participants in the Women's Health Initiative trial, which is a randomized trial of postmenopausal women aged 50 years or older. Although the risk for breast cancer dipped slightly for women who used estrogen-only HT for less than 10 years, the risk increased 30 percent for women who took estrogen for 15 to 19.9 years.

HT did not increase the risk for fatal breast cancers.

"Even though we saw an increased risk in developing breast cancer, we did not see an increased risk for dying from breast cancer," Chen said. She and her colleagues are currently researching this aspect of the findings.

This research was funded by the National Cancer Institute.