Breast Cancer Rates Mirror Changes in Screening and HRT Use

Allison Gandey

August 2, 2007 — A new study shows that trends in the incidence of breast cancer parallel changes in mammography screening and the use of hormone replacement therapy. Reporting in the August 1 issue of the Journal of the National Cancer Institute, the authors stop short of declaring a cause-and-effect relationship. Instead, they show a steady rise in breast cancer rates through the late 1990s — numbers that are consistent with the effects of mammography screening and the increasing use of menopausal hormone therapy. They also demonstrate that the recent decline in incidence is consistent with the drop in hormone use.
"Identifying the specific contributions of the potential causes of this long-term increase and the recent decrease in incidence has been challenging," note the investigators, led by Andrew Glass, MD, from Kaiser Permanente Northwest in Portland, Oregon. "Marked changes in rates of mammography screening and use of menopausal hormone therapy since 1980 have added further complexity."
In an accompanying editorial, Donald Berry and Peter Ravdin, MDs from the University of Texas MD Anderson Cancer Center in Houston, Texas, agree that, in observational studies such as those conducted by Dr. Glass and his team, the question of causation can be inferred but not directly proven.
They note that these latest findings are consistent with those of other databases and other populations — some published and some still in press. "An anomalous finding in the article of Glass et al, as compared with other databases known to us, is the decrease in the incidence of estrogen receptor negative tumors (about 50%) over the period 2002 to 2006," the editorialists write. "They have no good explanation for it, and neither do we."
Breast Cancer Rates Rose Steadily and Then Declined
Dr. Glass and colleagues analyzed time trends in breast cancer incidence, dispensed menopausal hormone therapy prescriptions, and screening mammography use among women enrolled in Kaiser Permanente Northwest, a large prepaid US health plan.
A total of 7386 incident invasive breast cancers were identified in plan members from 1980 through 2006. In women aged 45 years and older, the age-adjusted incidence of predominately estrogen receptor positive breast cancer rose from the early 1980s through 2001, then dropped by 18% from 2003 to 2006. Menopausal hormone therapy dispensing increased from 1988 to 2002 and then dropped by about 75%. Rates of mammography screening increased from 1980 through 1993 and then remained largely stable through 2006.
In July 2002, the Women’ s Health Initiative study, a randomized, double-blinded, placebo controlled clinical trial of estrogen plus progestin use among postmenopausal women for primary prevention of chronic disease was stopped early because the risks reportedly exceeded the benefits. Increased risks for breast cancer among women assigned to take estrogen plus progestin resulted in the termination of the trial.
"At the same time," the researchers write, "epidemiologic studies continued to document strong, statistically significant increased risks of breast cancer in women who used menopausal hormone therapy compared with women who never used it."
After the release of these findings, hormone replacement therapy use declined substantially in 2003. The investigators point to new data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, which showed a marked, statistically significant decline in breast cancer incidence in 2003 and 2004.
Other Unmeasured Risk Factors May Also Play a Role
The authors also note that this descriptive, population-level study examined aggregate data, so changes in other unmeasured risk factors might explain the observed incidence patterns.
"One limitation of the study that might be corrected in the future is that it was not done at the level of individual patient data," Drs. Berry and Ravdin add. "Merging this information at the individual patient level would enable a very powerful analysis of the menopausal hormone therapy question."
For example, they explain, the authors could track each woman in their database and see whether the women who stopped using menopausal hormone therapy were less likely to get screened and whether they were less likely to be diagnosed with cancer. They could also examine in a more detailed manner the correlation of the type and duration of menopausal hormone therapy use and the changes in breast cancer incidence on stopping such therapy.
"These additional analyses will be hopefully forthcoming from registries and data resources like those of the Kaiser Permanente Northwest group and might allow new insights into how to use menopausal hormone therapy with the lowest risk of negative effects and to the greatest advantage," they write.
"An important question is the effect the decrease in incidence will have on mortality, regardless of whether tumor growth is slowed or stopped by discontinuing menopausal hormone therapy," the editorialists emphasize. "The safe answer, again, is that we do not know. But the effect will probably be minimal to none."
J Natl Cancer Inst. 2007;99:1139-1141 and 1152-1161.