A special report in The New England Journal of Medicine concludes that the sharp decline in breast-cancer incidence in 2003, followed by a relative stabilization at a lower rater in 2004, is most likely related to the first report of the Women's Health Initiative (WHI) (JAMA 2002; 288:321-333. Risks and benefits of estrogen plus progestin in healthy postmenopausal women) and the ensuing drop in hormone-replacement therapy among postmenopausal women.

The report shows that the age adjusted incidence rate of breast cancer in women in the United States fell sharply by 6.7% in 2003, as compared with the rate in 2002. Data from 2004 showed a leveling-off relative to the 2003 rate with little additional decrease. The decrease was evident only in women who were 50 years of age or older and was more evident in cancers that were estrogen-receptor (ER)-positive than in those that were ER-negative.

The reports' lead author is Peter Ravdin, M.D., of the Anderson Cancer Center, and included investigators from the National Cancer Institute and the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed). Rowan Chlebowski, MD, PhD, a principal investigator/oncologist at LA BioMed, and the only researcher to participate in the 2002 reports of the trial evaluating estrogen plus progestin (which led to the decrease in menopausal hormone therapy use in 2003) and the 2006-07 studies outlining the subsequent decrease in breast cancer, states: "While the cause of the reduction is not definitive, the sustained decrease in new breast cancer diagnosed in the U.S. is a remarkable event. We estimate 44,000 fewer breast cancers over those two years (2003-04) and thousands more in the coming decades."

Researchers looked at several variables that could be responsible for such a decline. They looked for flaws in the data itself, changes in reproductive factors, changes in mammographic screening, changes in environmental exposures, changes in diet, and changes in use of hormone-replacement therapy. Only the use of hormone-replacement therapy changed substantially, with the total number of prescriptions for the two most commonly prescribed forms of hormone-replacement therapy in the United States - Premarin and Prempro - having their steepest declines starting in 2002 and particularly in 2003 (62 million scripts in 2000, 61 million in 2001, 47 million in 2002, 24 million in 2003, 21 million in 2004, and 18 million in 2005).

The reduction of hormone-replacement therapy could have caused a decreased incidence of breast cancer by direct hormonal effects on the growth of occult breast cancers, a change that would have affected predominantly ER-positive tumors. The rapidity of the change suggests that clinically occult breast cancers stopped progressing or even regressed soon after the discontinuation of the therapy. The hypotheses is that hormone withdrawal can rapidly influence the growth of breast cancer is supported by anecdotal reports of regression of breast cancer after discontinuation of hormone replacement therapy.

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Contact: Rowan Chlebowski
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)