Emory Study Provides First Biologic Evidence To
Support Hypothesis That High Endogenous Estrogen
Exposure Increases Breast Cancer Risk

August 5, 1996
Media Contacts: SarahGoodwin, 404.727.3366
Kathi Ovnic, 404.727.9371
http://www.emory.edu/WHSC/

The more female mice are exposed to the female hormone estrogen produced by their own bodies, the greater their risk for breast cancer, report researchers from the Emory University School of Medicine in the July 15 issue of Cancer Research. The study provides the first biologic evidence to support epidemiologic and clinical hypotheses associating early exposure to circulating, endogenous(produced by one's own body) estrogen and breast cancer risk.

The researchers developed a line (model) of transgenic mice whose genetic make up had been altered to overexpess an enzyme aromatase (int-5/aromatase) which catalyzes the conversion of androgens (male sex hormones) to estrogen -- the rate limiting step in estrogen biosynthesis.

Signs of precancerous and cancerous activity were apparent in the breast (mammary) tissue of every mouse in which this gene over expressed; none of their nontransgenic litter mates showed precancerous activity, reports first author RajeshwarRao Tekmal, Ph.D., assistant professor of Emory's Department of Gynecology and Obstetrics, and Winship Cancer Center. "...no studies have demonstrated the direct involvement of aromatase in the initiation of preneoplastic (precancerous) and/or neoplastic (cancerous) changes in mammary epithelium (tissue)," the authors say.

"The study reported here addressed this question directly, presenting evidence for the first time that the overproduction of int-5/aromatase in mammary glands of transgenic females leads to a range of morphological abnormalities... which are all indicative of preneoplastic changes. In contrast, we have not observed any histological (tissue) abnormalities in either nontransgenic litter mates or in a transgenic line (of mice) that had no significant overexpression of int-5/aromatase. These studies suggest clearly that the overexpression of the int-5/aromatase initiates various preneoplastic changes in mammary tissue. These changes may in turn increase the risk of developing breast neoplasia and increase susceptibility to environmental carcinogens."

The group also reports that the number of new cancer cells increases proportionally to the amount of overexpression by the estrogen precursor -- and that "these effects could be blocked completely by aromatase inhibitors." "The ongoing studies are aimed at understanding the mechanism involved in transformation of normal tissue to neoplastic tissue, and cooperation of tumor suppressor and other oncogenes involved in breast cancer in accelerating the cancer in these animals," Dr. Tekmal says. "This model provides a very useful system to investigate these possibilities and others such as preventive approaches to reduce the risk of breast cancer associated with endogenous estrogen by chemoprevention and dietary interventions." For more general information on The Robert W. Woodruff Health Sciences Center, call Health Sciences News and Information at 404-727-5686, or send e-mail to hsnews@emory.edu.

Cancer Risk Increases With Use Of Estrogen

Estrogen, the hormone doctors prescribe to their women patients who suffer from PMS, menopausal discomforts and related symptoms is undergoing intense review.

Researchers report new evidence that suggests long-term use of estrogen supplements, often referred to as Hormonal Replacement Therapy (HRT), increases the risk of dying from breast cancer by nearly 50%

Breast cancer kills about 44,000 U.S. women a year. It is the most frequently diagnosed cancer in women, exceeding 175,000 cases annually.

The latest study, published June 19, 1997 in the New England Journal of medicine, attempted to see what estrogen supplements do to women's risk of death. Like other studies, it found that estrogen reduces older women's risk of dying from a heart attack. But it found that the risk of breast cancer gradually increases and after a decade of use, the increasing cancer deaths begin to wipe out the advantages of avoiding heart trouble.

The Boston study involves121,700 women in the Nurses Health Study, including 3,637 who died during 26 years of follow-up. Meir Stampfer, M.D. an epidemiologist at the Harvard School of Public Health in Boston who headed the Nurses' Health Study, told the National Cancer Advisory Board "We have many ways to lower risk of heart disease. We have identified many risk factors that are modifiable, and a woman can alter her lifestyle in ways that will very markedly lower her risk of heart disease," Stampfer continued, "In contrast, we know very few ways that a woman can lower her risk of breast cancer. So we cannot simply say, well, because many more women die of heart disease, the benefits outweigh the risks."

Dr. Francine Grodstein, who directed the Boston study, noted that only women already at risk for heart disease live significantly longer as a result of the hormone pills.

For older women, the difficult question of whether to take estrogen for the rest of their lives now grows more complicated. Researchers say these studies urge caution when deciding about long-term estrogen use. The decision must be on a person-by-person basis, taking into consideration each woman's risk of heart trouble, breast cancer, and other diseases.

Nearly nine million American women take Premarin, Wyeth-Ayerst Laboratories' brand of postmenopausal estrogen, synthesized from pregnant mare's urine. Dr. JoAnn Manson, one of the researchers at Boston's Brigham and Women's Hospital warns that estrogen after menopause, "is being increasingly prescribed for long-term use to prevent heart disease and osteoporosis. Based on the uncertainty of the balance of benefits and risks, that should be done only with caution and not routinely."

A report by researchers from the Emory University School of Medicine in the July 15, 1995 issue of Cancer Research provided the first biologic evidence to support epidemiologic and clinical hypotheses associating early exposure to circulating, endogenous (produced by one's own body) estrogen and breast cancer risk. Their findings proved that the more female mice are exposed to the female hormone estrogen produced by their own body, the greater their risk for breast cancer.

Elaine Blume writing in the magazine: Journal of the National Cancer Institute says "prescribing replacement hormones - principally estrogen and progestins [ie; Provera a synthetic hormone compound with many serious side effects of its own]- produce a panoply of effects. And while most of these, including possible influences on mental acuity and incidence of Alzheimer's disease, appear to be positive, others both known and potential are adverse. The greatest concern of physicians is that administration of HRT on a long-term basis may increase a woman's risk of developing breast cancer. This trend worries some experts, and they are sounding the alarm."

Based on research by Ray Peat, PhD in the 1970's and physician John Lee a safe alternative to Hormonal Replacement Therapy already exists. Harvard medical physician John Lee's research and 20 years of case studies confirmed that natural progesterone (applied as a skin cream) can relieve menopausal symptoms and reverse osteoporosis without the risk of breast cancer. "Estrogen Replacement Therapy (ERT) was conceived in the late 1950's", Dr Lee explains, "this was the era of better living through chemistry - pharmaceutical companies were discovering the financial gains to be made by a philosophy; For every human ailment there is a drug that will cure it. Chemical and pharmaceutical companies [used] cleverly disguised public relations campaigns and 'planted' articles in magazines and newspapers extolling the virtues of synthetic hormonal drugs and reaped huge profits (and still do)." Dr Lee points out "I don't know any reason why any woman should be subjected to synthetic hormones. The natural hormones are available and are much safer and freer of side effects. Secondly, there is only a very small percentage of women who need estrogen supplementation. Most women go through menopause just fine, thankyou, and, at most need some progesterone. The third thing wrong [is] precancerous changes in tissue that show up in women on HRT or [who are] estrogen dominant will, in all likelihood, disappear after a few months of taking natural progesterone. This tissue growth is directly caused by estrogen, is very slow-growing, and poses no short-term threat. There is no reason to panic or rush into surgery." Citing extensive research and documentation the evidence is clear, "unopposed estrogen is carcinogenic for breasts". Natural progesterone is "beneficial in helping to keep the cancer cells under control...progesterone causes cancer to stop multiplying."

For woman, many natural products and common sense life style practices can help reduce breast cancer risks too. If you smoke, quit - now! Keep alcohol consumption to two drinks a day or less. Eat whole, fresh, preferably organic foods and avoid refined and processed foods, additives, preservatives and coloring. Drink plenty of clean water and avoid soda pop. Keep fat consumption to 20 to 25% of your calorie intake. Use olive oil and avoid hydrogenated oils. Eat a plant-based diet, emphasizing plenty of fresh organic vegetables, whole grains, legumes, nuts and fruit. Eat small portions of meat (including beef, pork and chicken) no more than two or three times a week. Take some antioxidant vitamins and if you're over 50, take a multivitamin as well. Get some moderate exercise, every day if possible. Keep your digestion working well by eating plenty of fiber and use probiotics (acidophilus) if necessary. Use some progesterone cream. Avoid doctors who want to put you on synthetic HRT and won't try natural, non-invasive options with no side effects first.