article

12.09.10

Breast Cancer Breakthrough?

Women scared away from hormone replacement therapy with estrogen because of a possible breast cancer link, take note: A startling study, released Thursday, says certain women who take estrogen alone actually have a reduced risk of breast cancer. Gail Sheehy talks to researchers.

A controversial study is adding new fuel to the debate raging over breast cancer and estrogen.

In recent years, thousands of menopausal women have been scared off hormone replacement therapy with estrogen because of its possible links to breast cancer, heart attacks, and strokes. But the startling new study, released Thursday by a Canadian research team, says certain women who take estrogen alone actually have a reduced risk of breast cancer.

“Our analysis suggests that, contrary to previous thinking, the data show that…for selected women [hormone replacement therapy] with estrogen alone it is not only safe, but potentially beneficial for breast cancer, as well as for many other aspects of women’s health,” said lead researcher Joseph Ragaz, M.D., medical oncologist and clinical professor in the School of Public Health at the University of British Columbia.

But other researchers are downplaying the findings, calling them old news. They caution that taking estrogen alone may increase the risk of endometrial cancer, counteracting the potential benefit.

Still, the findings will be welcomed by some of the menopausal women who suffer from hot flashes, memory lapses, painful sex, and bone loss that leads to fracture risk—but are afraid to take hormone replacement therapy with estrogen after previous warnings. Estrogen is the key hormone that solidifies protein in bones. The accelerated loss of bone in the first five to 10 years of menopause is responsible for a growing number of hip, spine, wrist, and femur fractures in older women, which leads to high mortality.

Fifteen years after the first big push in the 1960s to encourage women to stay youthful by using estrogen alone in the form of Premarin, a body of evidence demonstrated that estrogen caused an increase in endometrial cancer. Hormone replacement therapy fell out of favor, but through the years it returned to popularity after observational studies revealed that women who used estrogen combined with progesterone not only had a reduced risk of endometrial cancer, they lived longer and had an improved quality of life.

The Women’s Health Initiative, the first clinically sound randomized trial, set out to answer an important question: If hormone replacement therapy was so beneficial against heart attacks and menopausal symptoms, should all women be encouraged to use it? The estrogen arm of the trial was halted prematurely when it caused an overall increased risk of heart attacks and breast cancer.

Dr. Ragaz’s new findings come from a subset of the subjects in the Women’s Health Initiative study who had no family history of breast cancer and who had no prior breast disease. They were also younger than the average subjects, who were 62, and they started hormone replacement during the menopausal transition, not after.

In addition to a major quality of life improvement and a 20 percent to 40 percent reduction in rates of breast cancer, Dr. Ragaz said, the women who took estrogen alone also had 40 percent fewer heart attacks. There was no effect on clotting or strokes. But there was a 40 percent to 50 percent reduction of advancing osteoporosis, “which could affect millions of thin, fair-skinned women in North America,” he said.

In addition to a major quality of life improvement and a 20 percent to 40 percent reduction in rates of breast cancer, Dr. Ragaz said, the women who took estrogen alone also had 40 percent fewer heart attacks.

But the lead researcher in the Women’s Health Initiative, Dr. Rowan Chlebowski, called Dr. Ragaz’s findings old news. “This is almost identical to data we published from WHI in 2006 in [the Journal of the American Medical Association],” he replied testily when I read him Dr. Ragaz’s reinterpretation of his gold standard clinical study. “There is absolutely nothing new here that the scientific community has not had for the past four years.”

The Women’s Health Initiative “published this new data in small print,” Dr. Ragaz responded. “Instead of saying that estrogen alone reduces the risk of breast cancer in 70 percent to 80 percent of the women who took it, Dr. Chlebowski’s interpretation was ‘estrogen does not increase risk of breast cancer.’”

Dr. Chlebowski acknowledged his frustration that Dr. Ragaz will enjoy a high profile in the media as a result of his findings. “All the professional groups and regulatory agencies looking at this data don’t feel that exploratory subgroups give reliable enough evidence to drive practice,” Dr. Chlebowski said.

But the subset of women Dr. Ragaz has teased out is a majority of those who took estrogen alone. They may look at his data and decide that, given the good fortune to have no family history of this disease and no positive biopsies themselves, they can choose to use estrogen therapy to inhibit osteoporosis and heart disease.

Dr. Chlebowski also noted the risks of taking only estrogen: “There are some gynecologists who say they can manage patients on estrogen alone, and that’s a potential alternate strategy. But with 30 percent having endometrial proliferation after a year, is this something women should want to try?”

Dr. Ragaz told me his main contribution from the findings is a new theory that he says explains why the estrogen made internally, after menopause, is dangerous for the breasts, but why estrogen taken externally can be protective for the breasts. When women’s ovaries stop producing estrogen, he said, the body tries to compensate with an enzyme called aromatase, which converts testosterone into a carcinogenic form of estrogen in fat tissue. The growth of some breast cancers is promoted by aromatase. This explains the dangerous connection between obesity and a sedentary lifestyle and the increase in breast cancer, he said: “Our theory is that this carcinogenic form of estrogen in the breast, maximized during menopause, can be counteracted by taking external estrogen.”

Asked what was a safe progestin for women with a uterus to take, Dr. Ragaz noted that Prometrium has been on the market for seven years, but hasn’t been clinically tested. Women with a uterus who take estrogen alone can use an IUD that releases progestin. But again, it hasn’t been tested and is not commercially available.

Probing the original WHI findings is worthwhile, said Dr. Patricia Allen, director of The New York Menopause Center and a gynecologist affiliated with New York Presbyterian Hospital, but she warned of the cancer risks posed by using estrogen alone. “It is good news that scientists keep looking into the WHI data with a microscope," she said. “But there is no fully safe method for protecting women with a uterus who take estrogen alone from the high risk of endometrial cancer.” Dr. Allen believes that each woman must be treated individually based on the severity of her symptoms and her risk profile for harm from treatment with hormone therapy.

Gail Sheehy is author of 15 best-selling books, including the revolutionary Passages. Her new book, Passages in Caregiving: Turning Chaos Into Confidence, will be published May 4th by HarperCollins.