The latest study from the Women's Health Initiative (WHI) trial finds that postmenopausal women who take hormone replacement therapy (HRT) comprising estrogen plus progestin are at increased risk for both developing and dying from breast cancer. The researchers looked at outcomes of women who took HRT or placebo for a mean of 5.6 years and followed them for a mean of 11 years. The invasive breast cancer rate among those taking HRT was 0.42%, compared with 0.34% among those taking placebo. The rate of death from breast cancer in the HRT group (2.6 per 10,000 women per year) was approximately twice that in the placebo group (1.3 per 10,000 women per year). Among women taking HRT who developed breast cancer, 23.7% had positive lymph nodes, compared with 16.2% in the placebo group, and tumors tended to be discovered at later stages, in part because they're harder to detect in women taking HRT, a finding that appears to contradict earlier observational studies. The researchers concluded that, "Given these findings . . . a safe interval for combined hormone therapy use cannot be reliably defined."

In an accompanying editorial, Peter B. Bach, of Memorial Sloan-Kettering Cancer Center in New York City, wrote that, given the number of women who seek relief from menopausal symptoms, "it seems that additional randomized trials are needed specifically to determine whether lower doses or shorter durations of hormone therapy could alleviate menopausal symptoms without increasing cancer risk."

Earlier in 2010, the North American Menopause Society (NAMS) updated its recommendations for HRT based on rapidly evolving data. When patients desire HRT, wrote the panel of experts in women's health in the journal Menopause, "individualization of therapy is key to providing health benefits with minimal risks" and enhancing the quality of patients' lives.

"We recommend hormone therapy, for women who have troubling symptoms, at the lowest effective dose for the shortest amount of time," said Margery Gass, executive director of NAMS, in an interview with AJN.

In response to the new WHI study, Gass noted that the one to two extra deaths from breast cancer per 10,000 women is an increase similar to that seen in women who experience menopause later in life. If a woman could delay her own menopause by five years, Gass pointed out, she would have a similarly elevated risk of breast cancer as a result of changes in her own natural hormone levels.

However, Bach noted in his editorial that "what may seem like a small effect in the study apparently [had] an enormous effect in the population. Several years after use of hormone therapy plummeted [after the WHI trial was stopped in light of the harm HRT was apparently causing], breast cancer incidence also declined."

Gass believes that like many other treatments, HRT carries risks and benefits. "Each woman has to decide whether the benefits outweigh the risk," she said.

Perhaps in anticipation of such assertions, particularly from HRT advocates, Bach wrote that "discussing with patients the risk-benefit trade-offs in pursuit of an informed patient decision" may seem reasonable, but the effects of short-term use and lower dosages of HRT haven't been studied and "patient decisions are not valid when the information underlying the decision is itself speculative."-Carol Potera