Less Hormone Therapy, Less Breast Cancer

By Adriane Fugh-Berman, M.D.

The exodus from menopausal hormone therapy after the Women’s Health Initiative (WHI) proved that the risks of this therapy outweighed its benefits has resulted in a stunning drop in breast cancer rates. A new study shows that, in 2003, the year after the estrogen-progestin arm of the WHI was stopped, breast cancer rates plummeted by seven percent^1. It was expected that about 200,000 women would develop breast cancer in 2003, so about 14,000 fewer women were diagnosed with the disease than expected.

The decrease was most pronounced in women who were older than 50: women who were the prime target audience for hormone therapy. Breast cancer rates dropped 11 percent for women in their 50s and 60s -- and 7 percent for women in their 70s. In contrast, breast cancer rates dropped only 1 percent for women in their 40s, who are less likely than older women to take hormones.

The effects of hormone therapy are linked more strongly to estrogen-receptor (ER)-positive tumors than to estrogen-receptor-negative tumors. The decrease in cancer rates was twice as high (8 percent versus 4 percent) in ER-positive tumors than it was in ER-negative tumors. Among women 50-69 years of age, the reduction in ER-positive tumors was three times higher the reduction in ER-negative tumors (12 percent versus 4 percent). This study provides dramatic confirmation that combined hormone therapy increases the risk of developing breast cancer, particularly of developing ER-positive tumors.

Normally, one has to be cautious in interpreting cause and effect from associations. For example, birth rates that go up in a location in which the number of storks is also increasing doesn’t prove that storks bring babies. The dramatic drop in breast cancer rates, however, is extremely unusual -- especially without a change in other cancer rates. The decrease was seen in every cancer registry that reports data to the federal government. The fact that there were so many people using, and then abandoning, hormone therapy makes this situation into a sort of large-scale natural experiment.

The wide use of hormone therapy, of course, was due to marketing. Menopausal hormones were heavily promoted as a way to prevent disease during the 1990s. In fact, gynecologists were so convinced of its benefits that they ranked hormone use above smoking cessation as a positive means to prevent disease^2.Fifty-eight million prescriptions for hormone therapy were written in 1995; between 1999 and 2002, 90 million prescriptions were written annually^3.That means about a quarter of all women over 40 were taking hormones during this time.

Six months after the WHI found that menopausal hormones increased breast cancer rates and did not prevent cardiovascular disease, hormone prescriptions dropped by two-thirds. A year later, hormone prescriptions were down by 80 percent, compared to the number written before the WHI results were announced^4.Other studies have also found that hormone use has dropped. The National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey found that visits to physicians that resulted in hormone prescriptions being written decreased 43.6 percent from 2001 to 2003^5.

Fluctuations in breast cancer rates appear to closely follow the use of hormones. While hormones were being most heavily promoted, breast cancer rates increased: between 1990 and 1998, the incidence increased 1.7 percent per year. Breast cancer incidence began to drift down gradually after that, declining about 1 percent a year. Then, in 2003, the rates suddenly plummeted 7 percent. This is an astoundingly large drop; cancer rates just don’t change that fast without something major going on.

Hormone therapy is effective for hot flashes, and its short-term use may be worth the risks for some women with severe symptoms. But at this point, many lines of evidence have proven that menopausal estrogen-progestin therapy increases breast cancer risk. Don’t let anyone tell you otherwise.

Adriane Fugh-Burman, M.D., is an associate professor in the Georgetown University School of Medicine, Department of Physiology, and a former chair of NWHN.

REFERENCES

1. Ravdin PM, Cronin KA, Howlander N et al. "A sharp decrease in breast cancer incidence in the United States in 2003.” Data from MD Anderson, the National Cancer Institute, and Harbor UCLA Medical Center, presented at the San Antonio Breast Cancer Symposium, December 14, 2006.

2. Saver BG, Taylor TR, Woods NF et al. "Physician policies on the use of preventive hormone replacement therapy.” Am J Prev Med 1997;13(5):358-365.

3. Hersh AL, Stefanick ML, Stafford RS. “National use of postmenopausal hormone therapy: annual trends and response to recent evidence.” JAMA. 2004 Jan 7;291(1):47-53.

4. Majumdar SR, Almasi EA, Stafford RS. “Promotion and prescribing of hormone therapy after report of harm by the Women's Health Initiative.” JAMA. 2004 Oct 27;292(16):1983-8.

5. Hing E, Brett KM. “Changes in U.S. prescribing patterns of menopausal hormone therapy, 2001-2003.” Obstet Gynecol. 2006 Jul;108(1):33-40.