Study finds breast cancer decline linked to decreased hormone use

By Kristen Bole

Karla Kerlikowske, MD

Decreased use of postmenopausal hormone therapy since 2002—rather than a decrease in detection and diagnosis due to less screening—has contributed to a decline in the recorded incidence of breast cancer in the United States, conclude the authors of a study of more than 600,000 screening mammography examinations.

“Previous research has indicated a link between a drop in hormone therapy and a decrease in breast cancer rates, but this is the first study to demonstrate that link among a cohort of women undergoing routine screening mammography,” says lead author Karla Kerlikowske, MD, a staff physician at the San Francisco VA Medical Center (SFVAMC) and a professor of medicine, epidemiology, and biostatistics at the University of California, San Francisco (UCSF).

The study appears on line August 14, 2007 in the Journal of the National Cancer Institute, and will appear in the September 5, 2007 print issue.

The study authors prospectively collected data on 603,411 screening mammography examinations from January 1997 to December 2003 on women age 50 to 69 from four screening registries across the United States. They found that among women in the study annual rates of postmenopausal hormone therapy (the standard estrogen-plus-progestin combination) declined 7 percent between 2000 and 2002, and then a precipitous 38 percent between 2002 and 2003—in line with an overall national decline in hormone therapy use following the July 2002 release of Women’s Health Initiative findings showing an increased risk of breast cancer in women who took the therapy.

In turn, annual rates of estrogen receptor (ER)-positive invasive breast cancer—that is, tumors fueled by estrogen-progestin therapy—decreased 13 percent per year among the women in the study from 2001 to 2003.

The authors note a similar 14.7 percent annual decline in ER-positive breast cancer nationally from 2001 to 2004 among women age 50 to 69, as shown by a recent analysis from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program.

However, says Kerlikowske, the SEER analysis did not take into account differences in screening mammography rates among the women studied. She explains that since screening with mammography increases cancer detection rates by revealing cancers not palpable on clinical breast examination, this omission left unanswered the question of whether the national breast cancer decrease could be attributed to a decline in screening mammography and thus decreased detection of non-palpable cancers.

“We eliminated that variable,” says Kerlikowske. “Because our entire study population was screened regularly with mammography for the duration of our study, we can say that the national drop in cancer rates is most likely associated with decreased hormone use, and not with a decrease in screening mammography rates, as some critics of the earlier research have suggested.”

The study authors speculate that estrogen and progestin work “synergistically” to promote breast tumor formation and growth. They say that in the absence of those hormones, tumors may grow very slowly, stop growing, or “regress completely,” which would account for the drop in ER-positive breast cancer rates.

The authors conclude that women who require estrogen-progestin therapy to control postmenopausal symptoms should be encouraged to use the therapy “for the shortest time possible” in order to minimize an increase in breast cancer risk.

“Hormone therapy is one of the very few risk factors for breast cancer that you can modify,” Kerlikowske says.

Co-authors of the study are Diana L. Miglioretti, PhD, of the Group Health Center for Health Studies (GHCHS), Seattle, and the University of Washington (UW); Diana S.M. Buist, PhD of GHCHS; Rod Walker, BS, of GHCHS and UW; and Patricia A. Carney, PhD, of Oregon Health and Science University, Portland. All authors participate in the Breast Cancer Surveillance Consortium (

The research was supported by funds from the National Cancer Institute.
SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.