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A research triumph helps women


Breast cancer prevention has turned the corner, but there's still a way to go

Breast cancer incidence rates are taking a sharp downturn. A likely explanation is the cessation of postmenopausal hormone therapy in response to the report that hormone therapy increased breast cancer risk in the Women's Health Initiative trial. This story represents a triumph of epidemiology and clinical trial research.

Hormone therapy for hot flashes was first described in 1898 by German doctors who fed fresh cow ovaries to women after they had their ovaries removed. In 1942, it was approved for the treatment of menopausal symptoms.

In 1966 with the publication of a book, "Feminine Forever," the use of estrogen therapy increased dramatically. The authors of the book stated that women would shrivel up and become senile after menopause unless they took hormone therapy. Thus began the largest uncontrolled experiment in women's health -- the widespread long-term use of so-called "hormone replacement therapy" without any solid scientific basis.

After epidemiologists discovered the relationship between hormone therapy and uterine cancer in 1975, the use of estrogen therapy declined but then rebounded when, in the 1980s it was discovered that the addition of progesterone to the estrogen eliminated the uterine cancer risk. Prescribing skyrocketed.

In the Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, in 1996, we reported that the supposed long-term benefits of estrogen or estrogen and progesterone therapy might, in part, be due to the characteristics of the women who took the estrogen therapy, rather than to hormones themselves.

We also reported multiple links between markers of estrogen and breast cancer. Higher bone mineral density, a marker of higher estrogen levels, we found to be a determinant of the risk of breast cancer. We and others showed that higher blood levels of estrogens among women not taking hormone therapy was associated with an increased risk of postmenopausal breast cancer years later.

Overweight and obesity among postmenopausal women was shown to be the major determinant of postmenopausal blood estrogen levels and to be a major risk factor for postmenopausal breast cancer.

At the same time, investigators at the University of Pittsburgh led by Dr. Bernard Fisher demonstrated in clinical trials that drugs that block the effects of estrogen on the breast or production of estrogen could substantially reduce the risk of both first and recurrent breast cancer.

The decision to conduct the Women's Health Initiative, a clinical trial, randomly assigning women to hormone therapy or not, was blocked for many years in spite of excellent peer review and ultimately required direct support from the director of the National Institutes of Health. It was blocked because many felt that there was overwhelming evidence that hormone therapy was of great value.

Since WHI was reported, the results have been attacked for many inappropriate reasons. The drug that was tested was the wrong dose and the wrong duration. The population of women was too old. The characterization of each individual did not involve detailed genetic profiling. Moreover, the women who participated in the WHI and in other studies, who made a major contribution to women's health, were told that they would be injured by participating in the study. This clearly was not the case.

Ultimately, WHI results prompted many women to stop using postmenopausal estrogen plus progesterone therapy and that has now been demonstrated to translate into lives saved. The incidence of breast cancer declined in Pennsylvania, 8 percent between 2001 and 2003. Twelve hundred fewer women were diagnosed during that period.

We have turned a corner in<

12/27/2006
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