Breast cancer is second only to lung cancer as the leading cause of cancer death among women. This year alone, nearly 180,000 women in the U.S. will be diagnosed with invasive breast cancer, and some 40,000 will die from it, according to the American Cancer Society. There are some risk factors that a woman cannot control, such as her age and race as well as genetics, or family history, but there are also choices she can make to lower her odds of getting it. Among them, says a new study: steering clear of hormone replacement therapy, which new research confirms increases a woman's chances of developing breast cancer.

Researchers at the Kaiser Permanente Center for Health Research in Portland, Ore., concluded there is definitely a link between breast cancer and the use of menopausal hormone therapy, particularly estrogen-progestin treatment combinations. Since 1990, "breast cancer rates dropped in parallel with hormone use just as it rose in parallel to it," says oncologist Andrew Glass, lead author of the study published in the Journal of the National Cancer Institute.

Glass and his colleagues reviewed the medical histories of 7,386 women (in the database of Kaiser Permanente Northwest) diagnosed with invasive breast cancer between 1980 and 2006. They found that breast cancer incidence rose 25 percent from the early 1980s to the early 1990s—a period when an increasing number of women were getting mammograms and also undergoing hormone therapy to control menopause symptoms and prevent chronic disease. Glass acknowledges that the jump in breast cancer could be attributed to more women getting mammograms, because the test can find cancers that might otherwise go undetected until the disease has progressed.

But Glass notes that mammography rates among women in the Kaiser plan leveled off in the early 1990s, providing researchers with a perfect opportunity to study the relationship between breast cancer and hormone therapy use. They discovered that breast cancer incidence had moved in tandem with hormone use from the early 1990s onward. During the 1990s, the incidence of breast cancer climbed by about 15 percent, in synchrony with a growing number of women receiving hormone replacement therapy.

In 2001 the trend reversed: Breast cancer rates initially dipped gradually, but dropped sharply in mid-2002, when many women in the U.S. stopped hormone replacement therapy after the Women's Health Initiative, a large clinical trial involving estrogen-progestin therapy, was stopped after it was determined that the risks—most notably the increased likelihood of developing breast cancer—outweighed the benefits.

Consistent with the national trend, the number of women in the Kaiser plan taking hormone replacement therapy plummeted in 2002; from 2003 to 2004, breast cancer incidence slid 18 percent then continued on a downward trajectory. These patterns were largely limited to women aged 45 years and older, those most likely to use estrogen to control hot flashes, and to the types of breast cancer that grow when exposed to hormones.

"It's not exact cause and effect, but it's as close as you can be in epidemiology," Glass says. "There is no other explanation [besides hormone therapy] for what we've found."

"This is a corroboration…other analyses in the U.S. and Europe have shown the same thing," says Donald Berry, a professor and chairman of the biostatistics department at the University of Texas M.D. Anderson Cancer Center in Houston.

But does hormone therapy—once touted as being heart-healthy and preventing bone-thinning osteoporosis—offer any benefits? "To get rid of hot flashes and to make it through the night, it's probably a reasonable thing," Berry says. "But don't count on it having any long-term beneficial effects."

Glass stresses that there are other treatments for cardiovascular and bone health that are more effective and less risky. "The only reason to take…[hormones]…now is for menopausal symptoms," he says, "and it should be the smallest dose for the shortest time."