The decline in breast cancer incidence observed from 2002 to 2003 continued in 2004, supporting the hypothesis that the decline is tied to a decrease in use of hormone replacement therapy among postmenopausal women, according to a study published Thursday in the New England Journal of Medicine, USA Today reports (Rubin, USA Today, 4/19). Peter Ravdin, a research professor in the Department of Biostatistics at M.D. Anderson Cancer Center, and colleagues in December 2006 at the 29th Annual San Antonio Breast Cancer Symposium presented data showing that breast cancer incidence among U.S. women dropped by 7% from 2002 to 2003, possibly because of a decrease in HRT usage (Kaiser Daily Women's Health Policy Report, 12/18/06). For the study, Ravdin and colleagues analyzed data from the National Cancer Institute's Surveillance, Epidemiology and End Results study to determine the change in breast cancer incidence from 2001 -- the last full year before the government released findings of a large HRT study -- to 2004 (USA Today, 4/19). The overall decline in breast cancer incidence from 2001 to 2004 was 8.6%, including a 6.7% drop from 2002 to 2003. In 2002, results were released from the Women's Health Initiative study showing that HRT appeared to increase the risk of heart attacks and strokes, breast cancer and other health problems. As a result, millions of women ceased use of the drugs (Stein, Washington Post, 4/19). Prescriptions for HRT declined by at least 38% in 2003 and by an additional 20% in 2004. Researchers found that in 2003 and 2004, 30,000 fewer women developed breast cancer than would have been predicted by previous trends, and the incidence of breast cancer reached its lowest rate since 1987. Researchers found that the biggest decline in incidence -- 14.7% -- was in estrogen-receptor-positive tumors, in which estrogen promotes growth. In estrogen-receptor-negative tumors, the decline was 1.7% (Maugh, Los Angeles Times, 4/19). Researchers estimate that 16,000 fewer cases of breast cancer are being diagnosed each year because of the decline in HRT use (Washington Post, 4/19).

Contributing Factors
Ravdin said the evidence indicates that much of the decline can be attributed to changes in HRT use, noting that the largest drop was experienced by women older than 50, the population that most often uses the therapy. However, he added that the reasons for the decline likely are complex, according to the Wall Street Journal. Experts say that other contributing factors could include increased use of medications that lower breast-cancer risk, including the bone drug raloxifene, aspirin, anti-inflammatory drugs, calcium supplements and Vitamin D (Parker-Pope, Wall Street Journal, 4/19). In addition, the drop in breast cancer incidence could be attributed in part to a decrease in women getting mammograms, which dropped by 3% from 2003 to 2004 (Los Angeles Times, 4/19). JoAnn Manson, a Harvard University epidemiologist and investigator for the Women's Health Initiative, said, "Some women become less vigilant about having regular mammograms after stopping hormone therapy. If so, some of the decline in rates could reflect underdiagnosis." Researchers at the University of California-San Francisco are reviewing data for national screening program for breast cancer that includes hundreds of thousands of women, which should determine how much of the decline can be attributed to a decrease in screening (Wall Street Journal, 4/19). Other experts said the decline occurred too quickly to be attributed to hormone use, the Post reports. Hugh Taylor of Yale University said, "Even if there was a cause and effect, you wouldn't expect it to show up for five or 10 years. It just doesn't fit with what we know about the basic biology of breast cancer" (Washington Post, 4/19). Joseph Camardo of Wyeth, which manufactures the HRT product Prempro, noted that there was a 20% decline in hormone prescriptions in 2004 but that there was not a correlating sharp decline in breast cancer incidence (Los Angeles Times, 4/19). Camardo said, "I don't think anyone involved can say they have a specific alternative explanation, but I think other factors should be explored," such as the effects of other drugs, mammogram rates or changes in diet (Kolata, New York Times, 4/19).

Reaction
Ravdin said the study results do not mean that all women should discontinue use of HRT because the "risk of developing breast cancer from use of these hormones is relatively small, and for some women with menopausal symptoms, the benefits of hormone therapy are well worth the risk" (Peres, Chicago Tribune, 4/19). Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center said, "We can't prove" that the decline in breast cancer incidence is because of a decline in HRT use, "but it is such a substantial reduction that you would need something big to have occurred to explain it. If it is not hormone replacement therapy, we still need to explain it" (Los Angeles Times, 4/19). Marcia Stefanick of Stanford University said, "These data add to the message that we really should be discouraging women from initiating menopausal hormones. We need to stop underplaying those risks. They are very real" (Washington Post, 4/19).

Ovarian Cancer
A separate study published online Wednesday in the journal Lancet found that HRT increases the risk of ovarian cancer, USA Today reports (USA Today, 4/19). Epidemiologist Valerie Beral and colleagues at the Cancer Research U.K. Epidemiology Unit at the University of Oxford monitored 948,756 women in the Million Women Study for five years (Los Angeles Times, 4/19). Half of the women in the study had taken or were taking HRT drugs (USA Today, 4/19). Researchers found that HRT increased the risk of ovarian cancer by 20%, but when HRT treatment was terminated, the risk returned to normal levels. Beral and colleagues estimated that from 1991 to 2005 there were an additional 1,300 cases of ovarian cancer and 1,000 deaths in the United Kingdom as a result of HRT (Los Angeles Times, 4/19). Researchers found that the risk of ovarian cancer was small whether patients used HRT or not. For every 1,000 women taking hormones, 2.6 developed ovarian cancer, compared with 2.2 for women not taking hormones (Chicago Tribune, 4/19). In an editorial accompanying the study, Steven Narod of the University of Toronto said, "With these new data, we expect the use of [HRT] to fall further. We hope that the number of women dying of ovarian cancer will decline as well" (Los Angeles Times, 4/19).

< The NEJM study and a summary of the Lancet study are available online.

Broadcast Coverage
Three broadcast programs reported on the studies.

CBS' "Evening News": The segment includes comments Larry Norton of Memorial Sloan-Kettering Cancer Center (LaPook, "Evening News," CBS, 4/19). Video of the segment is available online.

NPR's "All Things Considered": The segment includes a discussion with Deborah Grady, a professor of medicine at UCSF, about the findings and alternatives to hormone replacement therapy (Norris, "All Things Considered," NPR, 4/19). Audio of the segment is available online.

NPR's "Morning Edition": The segment includes comments from Ravdin; Manson; and Bruce Ettinger, a researcher at UCSF (Knox, "Morning Edition," NPR, 4/19). Audio of the segment is available online.


"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

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