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Newswise — CHICAGO — 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 here 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.

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Presenter: Wendy Y. Chen, M.D., M.P.H.

Abstract Number: LB-60

Title: Long- term use of hormone therapy and breast cancer incidence and mortality

Author Block: Wendy Y. Chen, Walter C. Willett, Susan E. Hankinson, Bernard A. Rosner, Nurses Health Study Group. Harvard Medical School, Boston, MA

Background: The risk of breast cancer associated with longer-term use of both estrogen (ET) or estrogen + progesterone (E+P) hormone therapy (HT) cannot be determine from existing randomized controlled trials.Methods: The Nurses’ Health Study included 121,700 female registered nurses aged 30-55 in 1976 who have been followed with biennial questionnaires to medication use, risk factors and cancer incidence. Only postmenopausal women were included in this analysis. The main outcome was incidence of invasive breast cancer. We additionally evaluated the risk of fatal breast cancer (breast cancer diagnosis that resulted in breast cancer death).Results: During 1.57 million person-years of follow-up from 1980 through 2008, 5631 incident invasive breast cancers were diagnosed and 884 died of breast cancer. Breast cancer risk increased with duration of current E+P use without evidence for a plateau (e.g. RR 1.88 (95% CI 1.64-2.16) for 10-14.9 years and RR 2.35 (95% CI 1.90-2.92) for 15-19.9 years of use). More than 10 years of current ET use was also associated with increased breast cancer risk (RR 1.22 (95% CI 1.06-1.40) for 10-14.9 years and RR 1.43 (95% CI 1.22-1.68) for 15-19.9 years of use). Past E+P was also weakly associated with breast cancer risk. When the population was restricted to the same entry criteria as the Women’s Health Initiative trial, we also observed a non-significant deceased risk of breast cancer HT with current ET use similar in magnitude to that seen in the trial (RR 0.61 (95% CI 0.63-1.05) for < 5 years and RR 0.93 (95% CI 0.76-1.14) for 5-9.9 years), but still observed an increased risk with current ET users of 15-19.9 years (RR 1.30 (95% CI 1.07-1.59). Effects were stronger for ER positive tumors and among thinner women. Results were similar when limited to women who underwent regular screening. Although breast cancer incidence was increased in these groups, there was no increase in the risk of fatal breast cancer with either E+P or ET use (RR 1.05 (95% CI 0.67-1.68) and RR 1.08 (0.80-1.46) for 10-19.9 years of current use respectively).Conclusions: Both past and current E + P users and current long-term ET users were at increased breast cancer risk. We did not observe an increase in fatal breast cancer with HT use.

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American Association for Cancer Research Annual Meeting 2012