2004 Update Shows Continued Lower Breast Ca Incidence

HOUSTON—Reduced use of hormone replacement therapy (HRT) may explain the significant decline in the age-adjusted rate of new breast cancers that occurred in 2003 and was maintained in 2004. Researchers found a 6.7% decrease in new breast cancer diagnoses in 2003, compared to 2002, in an analysis of data gathered by NCI's Surveillance, Epidemiology and End Results (SEER) program. The sharp decline in new cases coincided with a large fall-off in HRT use.

Preliminary findings were presented at the 29th Annual San Antonio Breast Cancer Symposium in 2006 (see ONI January 2007, page 3). The new report includes the 2004 data, which show a leveling-off of breast cancer incidence from 2003 to 2004. "The decreased rates in 2003 were also present in 2004, meaning that the decline was not a 1-year wonder, a short-lived anomaly," said lead author Peter Ravdin, MD, PhD, professor of biostatistics, M.D. Anderson Cancer Center.

Regression analysis demonstrated that the decrease in incidence began in mid-2002 and began leveling off in mid-2003. A comparison of incidence rates in 2001 and 2004, which omitted the years in which the incidence was in the process of changing, showed an annual age-adjusted drop of 8.6% per year. Moreover, the decrease in incidence rate occurred only in women age 50 and older, and the drop was predominantly in estrogen-receptor (ER)-positive tumors.

"The decrease in breast cancer incidence seems to be temporally related to the first report of the Women's Health Initiative [WHI] and the ensuing drop in the use of hormone replacement therapy among postmenopausal women in the United States," senior author Donald Berry, PhD, head, Division of Quantitative Sciences, M.D. Anderson, and his colleagues reported (N Engl J Med 356:1670-1674, 2007). "The contributions of other causes to the change in incidence seem less likely to have played a major role but have not been excluded."

The NCI cautioned that "because this analysis is based on population statistics, the study does not prove a link between HRT and breast cancer incidence. Only a randomized trial could prove that."

HRT prescriptions plunged for the two hormone therapy drugs most often prescribed, Premarin and Prempro, from 61 million written in 2001 to 21 million in 2004, according to the authors. The decline occurred largely as a result of findings from the WHI, several studies involving 161,808 women that focused on the influence of HRT on heart disease, fractures, and breast and colorectal cancer. In July 2002, investigators halted the WHI trial after finding increased risks of breast cancer, heart disease, stroke, blood clots, and urinary incontinence associated with HRT use.

The SEER statistics used in the analysis came from nine cancer registries, which cover 9% of the US population. The researchers adjusted for delays in data reporting. During the 2001 through 2004 period, the breast cancer incidence increased 1.3% in women younger than age 50, decreased 11.8% in those aged 50 through 69, and dropped 11.1% in women aged 70 and older. Similar lower incidence rates were found for localized disease (11.3%), more advanced disease (13.6%), and primary breast cancers (13.7%), but not for contralateral second primary breast cancer or later disease, which showed nonsignificant increases.

The team noted several possible explanations other than reduced hormonal therapy for the drop in breast cancer incidence followed rapidly by a relative stabilization:

• A flaw in SEER reporting, "which seems unlikely" because decreases occurred in all nine registries.

• A major change in mammography screening rate. Screening in women age 50 to 65 dropped 3.2% in 2003, compared to 2000, but "such a change would seem insufficient to explain the observation."

• A change in screening patterns among women previously on HRT. "No published data are available showing a substantial decrease,Ķin such women."

• An incidence decrease is expected in a heavily screened population, such as that reported for prostate cancer. But "no sudden decrease has yet been reported for breast cancer incidence in heavily screened populations."

More breast cancers detected by mammography tend to be ER positive than those detected by other means, 80% vs 70%, but the difference in the percentages is small. "Thus, a drop in screening would result in an approximately equal decrease in ER-positive and ER-negative tumors, an expectation that differed from our findings," the investigators wrote. However, if the decrease in breast cancer incidence was associated with HRT discontinuation, the rapidity of the change suggests that clinically occult breast cancers stopped progressing or even regressed soon after discontinuation of HRT. "The hypothesis that hormone withdrawal can rapidly influence the growth of breast cancer is supported by anecdotal reports of regression of breast cancer after discontinuation of HRT," they wrote. Nonetheless, they acknowledged that the study "does not rule out some contribution from changes in screening mammography."