What Happened in 2003? Between 2002 and 2003, the incidence of breast cancer declined nearly 7 percent in the United States and remained low through 2004. This sharp decrease was reported last December, and since then researchers have been trying to explain the good news. Although there is no consensus and no proof of causation, the role of hormone therapy is attracting a lot of attention. The August 2 issue of the New England Journal of Medicine included seven letters to the editor regarding an analysis of the 2003 decline led by Drs. Berry and Ravdin that appeared in the journal last May. Some of the letters challenge the report's conclusion that the bulk of the decline is attributable to the sharp drop in hormone use, while others provide support for the theory. More support comes from a prospective study of screening and hormone use in more than 600,000 women from 1997 through 2003. A decline in mammography rates is unlikely to explain the recent decline in U.S. breast cancers while a drop in hormone use is a "more likely contributor," researchers in the Breast Cancer Surveillance Consortium reported online in JNCI August 14. Further insights may be provided by the Cancer Intervention and Surveillance Modeling Network, which is modeling the impact of HRT on breast cancer tumor progression and how risk changes when a woman stops using HRT.

A new study of women in a large U.S. health plan suggests that the use of hormone therapy played a key role in both the rise and decline of breast cancer rates in that population since the early 1980s.

The study describes changes in mammography screening, hormone therapy, and breast cancer incidence among women in the Kaiser Permanente Northwest health plan between 1980 and 2006.

The results link both mammography screening and hormone therapy to changes in breast cancer rates. But screening rates remained virtually constant from 1991 through 2006, leading the researchers to suggest that hormone therapy was responsible for the rise and decline of breast cancer rates since the early 1990s.

"The trends in hormone use go a long way toward explaining the fluctuations in breast cancer rates that researchers have been talking about for a long time," says Dr. Andrew Glass of the Kaiser Permanente Center for Health Research. He co-led the study with Drs. Robert Hoover and James Lacey of NCI's Division of Cancer Epidemiology and Genetics (DCEG).

The rates of women getting mammograms did drop slightly from 2000 to 2001 but rebounded in 2005 and 2006, according to findings in the August 1 Journal of the National Cancer Institute (JNCI).

Although the results are from a single population, the breast cancer rates among the Kaiser participants are nearly identical to statistics for the U.S. population.

"This study gives us one of the most comprehensive and up-to-date pictures of what's happening with breast cancer in the United States," says Dr. Lacey.

In the Kaiser population, breast cancer rates rose 26 percent from the early 1980s to early 1990s, paralleling increases in both mammography screening and hormone use. Rates then continued to rise but at a slower rate for another decade. This second rise parallels an increase in hormone use among the population at a time when mammography rates were stable.

After the health risks of taking estrogen-plus-progestin were revealed by the Women's Health Initiative study in July 2002, many Kaiser members, along with millions of other women, abandoned hormones. A sharp drop in breast cancer incidence among Kaiser members after 2003 paralleled a 75-percent drop in hormone therapy use in this population.

"Hormone therapy use was declining gradually in the period before the WHI results were announced," says Dr. Lacey. "People have focused on the dramatic 2003 drop in use, but some of the dynamics that led to the decline were in place earlier."

The researchers' observations are consistent with those from other studies, including some published and some still in press, note Drs. Donald Berry and Peter Ravdin of the University of Texas M.D. Anderson Cancer Center in the accompanying JNCI editorial.

"Hormone use remains an important public health issue," says Dr. Glass. "Millions of women are still taking hormones, and despite the research, some physicians believe these hormones are safe and effective and pose no harm to women."

The current study looked at time trends in practices and disease rates across the Kaiser population as a whole. Dr. Glass and his colleagues are developing plans to use the Kaiser database to link pharmacy, screening, and disease records for individual women. The results could potentially clarify whether women who stopped hormone therapy were less likely to get screened and less likely to be diagnosed with cancer.

The current Kaiser study, which is a follow-up to a 1990 study by Drs. Glass and Hoover, has produced clues to a complicated puzzle at a time when they are needed.

"What we have here is a good example of a natural experiment occurring over time," says Dr. Glass. "You can see the play of the different forces as they take hold."