Breast cancer: Estrogen-only pills may cut long-term risk

Led by Garnet Anderson, latest Women's Health Initiative study shows more than 20 percent reduction in cancer risk, 63 percent reduction in deaths for short-term estrogen users
"These latest results should provide reassurance about breast safety of estrogen use for durations of about 5 years for women with a hysterectomy seeking relief from postmenopausal symptoms," said Dr. Garnet Anderson, lead author. Photo by Dean Forbes

Women who use the estrogen-only form of hormone replacement therapy appear less likely to develop breast cancer in the longer term, according to new Hutchinson Center research published online March 7 in The Lancet Oncology.

Led by Dr. Garnet Anderson of the Public Health Sciences Division, the follow-up study of more than 7,500 women from the Women's Health Initiative who took estrogen for about 6 years and then stopped found they are more than 20 percent less likely to develop breast cancer and remain significantly less likely to die from the disease than those who never used HRT. The protective effect remained for nearly 5 years after stopping treatment.

The researchers found a 23 percent reduction in the incidence of invasive breast cancer compared with placebo during an overall follow-up period of nearly 12 years. Women in the estrogen group who developed breast cancer had a 63 percent reduction in deaths from the disease compared with those in the placebo group.

"These latest results should provide reassurance about breast safety of estrogen use for durations of about 5 years for women with a hysterectomy seeking relief from postmenopausal symptoms," said lead author Anderson. Aaron Aragaki of PHS and other WHI investigators also contributed.

The key findings:

  • Women with prior hysterectomy who are suffering from menopausal symptoms can be assured that short-term estrogen use (up to about 5 years) to relieve these symptoms does not increase breast cancer risk.
  • Estrogen should not be used for breast cancer prevention because of other risks, primarily for strokes, and because the observed benefits do not seem to apply to women at increased risk of breast cancer, the subgroup of women for which a chemo-preventive approach is most relevant.

In 1993, the WHI trial of estrogen alone was established to investigate the effects of conjugated equine estrogen on chronic disease. Nearly 11,000 postmenopausal women aged 50 to 79 years old who had previously had a hysterectomy were given estrogen or placebo over a period of nearly 7 years. The trial was stopped in 2004 (a year earlier than planned) because of an increased risk of stroke and blood clots.

In this new analysis, Anderson and colleagues report the overall effects of estrogen use on breast cancer incidence and mortality, including extended follow-up of 7,645 women (78 percent of the original surviving members) who were tracked from March 2005 until August 2009, an average of 4.7 years after stopping estrogen therapy.

The lower risk of breast cancer was seen only in women without a history of benign breast disease or a strong family history of breast cancer.

"The continued post-intervention effect of estrogen on breast cancer incidence is akin to that reported for other hormone-targeted drugs shown to reduce breast cancer incidence," the authors said.

However, they caution against using estrogen as a preventive measure, given the lack of benefit noted in higher risk populations and the additional risk of stroke and blood clots.

Longtime Hutchinson Center contributors to WHI

Anderson praised the PHS researchers and staff who have coordinated WHI efforts for nearly 20 years. Behind-the-scenes contributors to the latest findings include the WHI outcomes group, especially Dessie Levias, Lori Proulx-Burns and Beth Burrows. "They've done a phenomenal job of managing the medical records for the 161,000 women in WHI and coding over 20,000 cancer cases," Anderson said.

She also complimented Doris Nodtvedt and her group, who coordinate thousands of mailings monthly to keep in touch with WHI participants, as well as the study's team of programmers, data managers, statistical analysts and IT support. "They all provide incredible infrastructure on which we rely every day to be productive, informed and connected," Anderson said. She credited longtime WHI coordinating center project managers Bernedine Lund and Susan Anderson for providing crucial technical and administrative oversight.

[Adapted from a Lancet Oncology news release]


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