Estrogen study provides new impetus for development of colon cancer drugs

BOSTON -- The female hormone estrogen may hold important clues for scientists working on new therapies for colon cancer, a study by Dana-Farber Cancer Institute researchers suggests.

Using data from a long-running study of womenís health, the investigators found that postmenopausal women with colon cancer lived longer and had less likelihood of dying of the disease if they had been taking estrogen supplements within five years of their diagnosis. In this new study, published in the Dec. 20 issue of the Journal of Clinical Oncology, investigators examined the effect of estrogen use on the survival of older women already diagnosed with the disease.

While estrogen use has dropped sharply among postmenopausal women in recent years, due to concerns about its role in heart disease and breast cancer, numerous studies have shown it significantly lowers the chances of developing colorectal cancer. The researchers stress that these findings do not mean estrogen should be viewed as a treatment or preventive therapy for colon cancer, considering the other health risks associated with its use. However, the research may guide the development of other, safer colon cancer drugs.

"This study provides a rationale to further study the basic mechanism by which estrogen influences the development and progression of colon cancer," states lead author Jennifer Chan, MD, MPH, of Dana-Farber. "By understanding how estrogen offers potentially beneficial effects in some types of cells yet deleterious effects in others, it may be possible to design therapies that are effective against colon cancer without posing a significant risk of other problems."

Estrogen supplements have been taken by millions of older women as a way of staving off some of the problems associated with menopause, such as hot flashes and bone loss, but the number has declined considerably since 2002. That year, investigators reported that, for many women, the supplements carried more health risks than benefits.

The research by Chan and her colleagues drew on data from 834 postmenopausal women enrolled in the Nurses' Health Study -- which has tracked the health of more than 100,000 female nurses since 1976 -- who had been diagnosed with colon cancer between 1976 and 2000. The researchers found that, compared to women who had never used estrogen, those using the hormone at the time of diagnosis had a 36 percent lower chance of dying of colon cancer and a 26 percent lower chance of dying of any cause. The benefit was most pronounced in women who used estrogen for less than five years. Using it for longer, however, did not seem to provide a similar advantage.

The authors do not know why using estrogen for more than five years did not improve women's chances of survival. They theorize that colon tumors that developed in women who had used estrogen for many years may have been less susceptible to estrogenís growth-slowing effects.

The precise way by which estrogen foils the growth of colon cancer cells is unclear, as well. The study authors offer three possibilities: the hormone directly suppresses the cells' growth; it decreases the production of bile acids which are known to spur cancer; or it blocks certain genetic changes within colon cells that lead to cancer.

"Further efforts are needed to bring these mechanisms to light," comments Chan, who is also an instructor in medicine at Harvard Medical School. ďOur study provides an important rationale for undertaking those studies."

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The studyís senior author is Charles Fuchs, MD, MPH, of Dana-Farber. Co-authors are Jeffrey Meyerhardt, MD, MPH, of Dana-Farber, Andrew Chan, MD, MPH, of Massachusetts General Hospital, Edward Giovannucci, MD, ScD, and Graham Colditz, MD, Dr.PH, of the Channing Laboratory at Brigham and Womenís Hospital, home of the Nurses' Health Study.

Funding for the study was provided by a grant from the National Institutes of Health.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.


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