One of the most controversial drug issues of the past several decades has been the safety of hormone replacement therapy (HRT). For years, many physicians encouraged women to take drugs like Premarin, Provera or Prempro as soon as they began having hot flashes. HRT was supposed to keep bones strong and the heart healthy. Concerns about breast cancer were often downplayed.

Even after the Women’s Health Initiative suggested that women taking HRT were at higher risk of breast cancer, many health professionals were skeptical. Now, however, the research seems even more compelling.

When all the bad publicity about HRT came out, millions of women stopped taking hormones. Within a year, breast cancer rates had dropped by almost 7 percent. That might not seem like much, but in the world of cancer epidemiology it was the equivalent of a tsunami.

Normally, the number of new cancer cases doesn’t change very much from year to year. Many scientists didn’t believe there would be such a dramatic drop as a result of declining HRT prescriptions. Some hormone enthusiasts tried to rationalize the results by suggesting that women were not going in for mammograms, so the discovery of new cases would be delayed.

The second year of data is now in, however, and it reinforces the earlier findings. New breast cancer cases are still down (New England Journal of Medicine, April 19, 2007).

The biggest decline (more than 11 percent) came among women who were 50 or older. Scientists compared statistics from 2001 (at the peak of the HRT bandwagon) with those from 2004 (after HRT prescriptions had dropped 38 percent). Estrogen-positive tumors were reduced by nearly 15 percent in that age group.

It all makes sense pharmacologically. Researchers have known for decades that estrogen can act like fertilizer for breast cancer. This can be inferred from at least three sources of information: animal research, epidemiology and the effectiveness of anti-estrogen breast cancer treatments.

As far back as 1977, veterinarians had identified estrogen as a carcinogen for breast tissue. Epidemiologists also linked higher lifelong estrogen exposure to a greater risk of breast cancer in humans. Women who start menstruating at younger ages and go through menopause at older ages are at higher risk. That is presumably because they have been exposed to their natural estrogen for a longer period of time.

The most important advances in breast cancer treatment during the past couple of decades involve ways to block estrogen. Tamoxifen was the first anti-estrogen and is still an important way to prevent recurrence. Now, drugs that keep the body from making estrogen (aromatase inhibitors like Arimidex, Aromasin or Femara) have also become valuable tools in the fight against breast cancer.

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