By Margarita Nahapetyan
Two large new Stanford University studies found that taking estrogen plus progestin as HRT (hormone replacement therapy) for menopausal symptoms, increases the risk of breast cancer, but that risk drops about two years after stopping the hormone therapy.
The Stanford research is a follow up to the Women's Health Initiative (WHI) report, a national women's health study, which found that postmenopausal women taking an estrogen plus progestin combination at least for five years, were at greater risk of heart disease, stroke, blood clots, and breast cancer (and decreased the risk of colorectal cancer and bone fractures), compared to women taking a placebo.
The researchers examined the data of more than 15,000 women who participated in the original WHI trial, and more than 41,000 women took part in a separate observational research. The results for both groups were pretty much similar. Among women from the clinical trial who quit using HRT, the number of breast cancers diagnosed dropped 28 per cent within a year.
The WHI did not have enough financial support and, therefore, the study could not proceed any further. Use of hormone therapy in the U.S. fell from 60 million prescriptions in 2001 to 20 million in 2005. Since that time, breast cancer diagnoses have also dropped.
When Dr. Rowan Chlebowski of the Los Angeles Biomedical Research Institute and other researchers reanalyzed the effects of HRT, they discovered that during the first two years, the HRT group that took part in the clinical trial, had fewer breast cancer diagnoses than the placebo group. However, the number of breast cancer cases in that group increased over the more than 5-year study period. The risk fell drastically in both groups after they quit the pills, even though both groups had mammograms with similar frequency.
"There was a rapid decline in breast cancer incidence after stopping hormones, while mammography use didn't change between the groups," Chlebowski explained.
For example, in the observational research, the incidence of breast cancer in the HRT group was nearly two times as high as in the placebo group, but the difference faded approximately two years later, as women stopped taking the hormones.
The unpleasant news is that women who still continue the combined HRT for five years and more are at greater risk for developing breast cancer, the new analysis reported.
"A woman who continues combined hormone therapy after about five years would double her personal annual risk of breast cancer," said Dr. Marcia Stefanick, a professor of medicine at Stanford University School of Medicine and a co-author of the analysis. That risk chances went up even when adjustments were made for age, which increases risk on its own, she said. "And what happens with risk after that five years of use is yet not known."
"I would encourage women to try and make it through menopause without starting hormone treatment, and if you do start, go for the lowest dosage and the shortest duration,'' concluded Stefanick.
Another study, reported recently in the journal Cancer, also found that two years might be a "safe" period for the use of combined HRT. Eugenia Calle, former vice president of epidemiology for the American Cancer Society, and her colleagues examined about 68,000 postmenopausal women who were cancer-free at the beginning stage of the study in 1992. The hormone use of all women have been evaluated, as well as the risk of getting breast cancer. The women were being followed till 2005.
The researchers identified a possible gap between 2 to 3 years in which there was no sign of increased breast cancer risk in women taking combination of hormones. "In terms of our data, it looks pretty safe; there is absolutely no increased risk," said Eugenia Calle. But she warns that that discovery of a possible "safe" period "needs to be replicated in other studies ... the numbers are small in our study."
Both Stefanick and Chlebowski note that use of HRT can increase breast density, and therefore, making it much more difficult to reveal breast cancers. "Do we have evidence that there really are fewer cancers or are we seeing that it's harder to detect them?" Stefanick asks. "If you have something that interferes with diagnosis, you are going to have a really hard conceptual time defining a completely safe interval," added Chlebowski.
Chlebowski acknowledged that the findings bolster, if not definitively prove, the causal connection between use of combination hormone therapy and some breast cancers. He said that some physicians may still remain skeptical about the connection. But anyway, there is strong enough evidence to make both doctors and patients think twice about continuing combined HRT for more than three to five years.