Long-term estrogen therapy linked to breast cancer risk

Long-term estrogen therapy may be related to a higher risk of breast cancer among postmenopausal women who have had a hysterectomy, according to an article in the May 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Previous studies have linked the use of hormone therapy to breast cancer among postmenopausal women, but have primarily focused on the hormone combination of estrogen plus progestin, according to background information in the article. Recently released results from the Women's Health Initiative (WHI), a large clinical trial of hormone therapy, found no significant link between estrogen therapy and breast cancer in women who took the hormone for seven years.

Wendy Y. Chen, M.D., M.P.H., Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, and colleagues evaluated women who were part of the Nurses' Health Study, a group of female nurses that have been followed since 1976. In 1980, 11,508 women from the study were postmenopausal and had had a hysterectomy. Every two years the researchers enrolled all the additional women who become postmenopausal and had a hysterectomy, so 28,835 women were included by the end of the study in 2002. Women were asked by questionnaire every two years if they used hormones and whether they had developed breast cancer. For women who developed breast cancer, the researchers obtained permission to review the women's medical records, which they used to record the hormone receptor information. Tumors were classified as positive or negative for estrogen receptor or progesterone receptor based on how they responded to specific hormonal therapies.

Throughout the study period, 934 invasive breast cancers developed, 226 among women who had never used hormones and 708 among women who were using estrogen at the time. The longer a woman used estrogen, the higher her risk of breast cancer. Those who had been taking estrogen for fewer than 10 years did not appear to have a higher risk than those who had never taken hormones, but those who had been taking estrogen for more than 20 years had a significantly increased risk. The association was strongest for cancers that were estrogen receptor positive and progesterone receptor positive. The results were similar when the researchers evaluated only women who were older than age 60; only women who had begun estrogen therapy after reaching age 50; and only women who were at least age 50 and had undergone a hysterectomy, even if they had not gone through menopause.

"In conclusion, we found that estrogen therapy was associated with an increased risk of breast cancer with longer-term use," the authors write. "Although current use of estrogen therapy for less than 10 years was not associated with a statistically significant increase in breast cancer risk, the WHI has shown an increased risk of stroke and deep-vein thrombosis in the same time period. Women who take estrogen therapy for prevention or treatment of osteoporosis typically require longer-term treatment and should thus explore other options, given the increased risk of breast cancer with longer-term use."

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(Arch Intern Med. 2006; 166: 1027-1032. Available pre-embargo to media at www.jamamedia.org.)

Editor's Note: This study was supported by a grant from the National Institutes of Health, Bethesda, Md.


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