Long-Term Estrogen Use Linked to Breast Cancer Risk

New research by Harvard scientists sheds more light on the relationship between estrogen-only hormone replacement therapy and breast cancer. In a study published in the Archives of Internal Medicine, a group from Harvard's Channing Laboratory and the Dana-Farber Cancer Institute says that using estrogen for more than 15 years significantly raises breast cancer risk.

The report comes just weeks after researchers from the Women's Health Initiative (WHI) said in a separate study that estrogen doesn't increase breast cancer risk.

Confused? The key is in how long women use the hormone therapy. The 2 studies looked at different durations of hormone use, and that accounts for their different results.

Both studies involved only women who had had a hysterectomy, because they are the only ones who can use estrogen-only hormone therapy. It is typically prescribed to relieve hot flashes and other symptoms of menopause, but can also help limit bone loss (osteoporosis) that comes with menopause.

Women who have not had a hysterectomy but want relief from menopausal symptoms typically take a combination of estrogen and progestin. This so-called combination therapy is associated with a higher risk of breast cancer even when taken for a shorter time.

New Findings Complement Earlier Ones
The WHI randomly assigned women who'd had hysterectomy to use estrogen-only hormone therapy or a placebo, and tracked breast cancer rates for about 7 years. In that time, they didn't see any increased risk of breast cancer among the women on hormones.

But the new analysis, which was part of the large Nurses' Health Study, followed women for more than 20 years. These women weren't randomly assigned to take the hormone or a placebo like in the WHI. Instead, the researchers just asked them about their hormone use periodically over the course of the study (1980-2002).

By the end of the study period, nearly 29,000 women were enrolled, and there had been 934 cases of breast cancer .

There was no real increase in breast cancer risk among women who used estrogen for 10 years or less. That finding fits right in with the Women's Health Initiative results, which also found no higher risk of breast cancer with just a few years' use.

Between 10 and 15 years of use, the risk of breast cancer started to rise slightly, but it did not reach statistical significance. Women who took estrogen for at least 15 years had a higher risk of developing breast cancer with estrogen and progesterone receptors. This is the most common type of breast cancer and typically responds well to treatment with hormone therapies like tamoxifen or aromatase inhibitors.

After 20 years of hormone use, women had a 48% higher risk of developing any kind of breast cancer. That amount was also statistically significant.

Use Estrogen for As Little Time As Possible
Experts say the new study underscores the importance of following the advice many doctors now give women: if you're going to use hormone therapy, use it for as short a period as possible and at the lowest dose possible.

"You probably shouldn't take hormone therapy if you don't have to," said Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society. "Although there may be some benefits from hormone therapy, the potential harms far outweigh those benefits."

There are safer drugs to treat some of the other conditions -- like osteoporosis -- that estrogen might be used for, he added.

Women who do need hormone therapy to treat symptoms of menopause can breath a little easier now that 2 large studies have found that short-term use doesn't appear to raise breast cancer risk. However, they should also remember that estrogen carries other risks, like a higher chance of strokes and blood clots.

Citation: "Unopposed Estrogen Therapy and the Risk of Invasive Breast Cancer." Published in the May 8, 2006, Archives of Internal Medicine (Vol. 166, No. 9: 1027-1032). First author: Wendy Chen, MD, MPH, Harvard Medical School and Dana-Farber Cancer Institute.