the trouble with tamoxifen
Article by Dr. Zoltan P. Rona MD MSc

In early April, 1998, a media blitz hailing tamoxifen as a breakthrough in the prevention of breast cancer created controversy within holistic and mainstream medical communities alike. The sudden enthusiasm for a drug used primarily in the treatment of early and advanced stages of breast cancer stemmed from the results of an abruptly terminated study conducted by the U.S. National Cancer Institute (NCI). This study concluded that tamoxifen can cut the incidence of breast cancer in high risk women by 45 per cent. Doctors were quoted in all the world¹s major newspapers singing the praises of this new milestone for breast cancer prevention.

Some scientists, however, expressed a different view. According to Dr. Trevor Powles of the Royal Marsden Hospital in London, the excitement about tamoxifen is unjustified:

"There has been significant over-reaction. Even though there has been a reduction in breast cancer cases, we are

still only talking about a (relative) handful of women."

Some physicians routinely prescribe tamoxifen for most breast cancer patients but studies show little or no survival benefit among women with pre-menopausal, estrogen receptor negative breast cancer, even when given after chemotherapy in pre-menopausal women.

The tamoxifen "breakthrough" was seen as nothing more than hype by Professor Michael Baum, a British authority on breast cancer:

"This is not the way one goes about promoting scientific results."

Tamoxifen has been used as a breast cancer therapy since the 1970s but is not approved for use in Canada for prevention purposes. This is likely to change with drug company and physician pressure on Health and Welfare Canada¹s HPB.

The long term safety of tamoxifen use in healthy women has never been established. Many of tamoxifen's side effects are relatively benign and include hot flashes, nausea, weight gain and menstrual irregularities. Less than 20% of women taking tamoxifen experience serious side effects but these side effects can be lethal or permanent.

It is a well documented fact that tamoxifen is carcinogenic (causes cancer). In particular, tamoxifen can cause uterine cancer but cancers of the liver, ovaries and gastrointestinal tract have also been reported. A study at Johns Hopkins by Yager and Shi found that tamoxifen is a promoter of liver cancer. On February 22, 1996, a division of the World Health Organization, the International Agency for Research on Cancer, declared tamoxifen a Group I carcinogen for the uterus. In the abruptly curtailed NCI study, 33 women who took tamoxifen developed endometrial cancer.

Tamoxifen can also cause many hormonal imbalances and toxicities including the development of blood clots, osteoporosis and visual disturbances caused by retinopathy (retinal damage), corneal changes, optic nerve damage and cataracts. None of these may be reversible on discontinuing the drug. In the NCI study, 17 women who took tamoxifen suffered blood clots in the lungs and 130 developed deep vein thrombosis (blood clots in major blood vessels). In pre-menopausal women, tamoxifen causes bone loss of 1.7% annually. Side effects such as confusion, depression, memory loss and fatigue have also been reported.

"You need to be clear about what the risks are so you¹re not trading one disease for another."

Georgia Wiesner, medical director

Center for Human Genetics

University Hospitals, Cleveland

In November 1995, the National Cancer Institute called for term limits on tamoxifen therapy (no more than five years) and said that results "indicated the lack of additional benefit for tamoxifen beyond five years, and raised the possibility that continued use might be detrimental."

Another drawback to tamoxifen is that virtually all patients with metastatic disease eventually become resistant to the drug. The NCI trial and a similar trial in Scotland indicated that tamoxifen use for longer than five years could actually fuel the growth of breast cancers, as well as cancers in other sites.

Tamoxifen Deaths

Tamoxifen for prevention has been equated by some to Russian roulette. Others believe that it is no different from the typical toxic drug approach to prevention taken by conventional Western medicine. This type of side effect laden preventive medicine includes the use of aspirin for heart disease prevention, HRT (hormone replacement therapy or horse urine replacement therapy) for osteoporosis prevention, contaminated vaccines to prevent the flu and hepatitis and steroids for prevention and treatment of just about anything else. A recent University of Toronto study published in the Journal of the American Medical Association supports the concept that this is a very dangerous trend. In this study, Dr. Bruce Pomeranz and his colleagues concluded that the average number of deaths per year from drug reactions in the U.S. from 1966 to 1996 was about 106,000, making death from drug reactions the fourth or fifth leading cause of death from all causes.

Should high risk women get tamoxifen as a preventive agent? Doctors and their patients must work the odds (gamble) in deciding on tamoxifen prescriptions since the guidelines for its use are rather nebulous at this time. Criticisms about drug toxicity are usually sloughed off by proponents with the much abused smokescreen phrase, "weighing the risk to benefit ratio". Weighing the risk to benefit ratio, however, is an illogical exercise when one of the risks of this "preventive" therapy for a healthy woman is death. One death from tamoxifen toxicity is one death too many and at least two deaths occurred in the tamoxifen treated group in the NCI study.

Safer and Better Alternatives

Tamoxifen is a synthetic hormone derived from the carcinogenic hormone DES (diethyl stilbesterol) which caused vaginal cancer in the offsprings of women who took the drug during their pregnancies. Tamoxifen was first marketed in 1977 as a treatment for advanced breast cancer. It is said to inhibit breast cancer due to its anti-estrogenic effects, blocking the uptake of estradiol and estrone, the cell-proliferating estrogens. This protects the breast tissue from the cancer-promoting estrogens (natural or chemical) present in the body. A growing number of doctors (see Dr. John Lee¹s "What Your Doctor May Not Tell You About Menopause") point to research that indicates that the same results can be achieved by using natural progesterone as a transdermal cream.

Another natural product with proven anti-breast cancer activity is melatonin. In one recent study, scientists at Tulane University School of Medicine grew human breast cancer cells in the laboratory and then added melatonin to some of the cultures. They found that estrogen-receptor-positive cells treated with melatonin grew one-fourth to one-half as fast as untreated cells did. Melatonin, like tamoxifen, had no effect on cancer cells that lacked estrogen receptors.

According to Dr. Steven Hill, an assistant professor at Tulane, "Melatonin may be a naturally occurring anticancer compound. The more a breast cancer is estrogen receptor positive, the more dramatic the response may be. Melatonin appears to work in a very novel way, by somehow decreasing the number of estrogen receptors the cells have, which in turn cuts the amount of tumor-promoting estrogen that enters them."

There is also growing evidence that breast cancer can be prevented with soy isoflavones, high doses of antioxidants, essential fatty acids, Coenzyme Q10, milled flax seed and other high fiber sources, estriol (the anticarcinogenic "forgotten" estrogen), 27-deoxyacteine, an extract of black cohosh and many other natural approaches.

Dr. A.V. Costantini, retired Head of the World Health Organization (WHO) Collaborating Center for Mycotoxins in Food at the School of Medicine in Freiburg, Germany ( see the new book "Prevention of Breast Cancer, Hope at Last") has also advanced a well documented theory that fungal mycotoxins and their eradication from the body are the best form of prevention against breast cancer. It is interesting to note that tamoxifen is antifungal. Dr. Costantini postulates that this is the reason for some of its effectiveness in breast cancer therapy. If his theory is valid, it would help explain the efficacy of vegetarian diets (red meats are a heavy source of fungal mycotoxins) and many natural cancer therapies. Of course, there are less toxic, more effective natural and prescription antifungals that can be used in place of tamoxifen (see Jeanne Marie Martin¹s "The Complete Candida Yeast Guidebook") to rid the body of fungi and their mycotoxins.

For more information on these natural alternatives, see also Susun Weed¹s "Breast Cancer? Breast Health The Wise Woman Way" as well as "Breast Cancer, What You Should Know (But May Not Be Told) About Prevention, Diagnosis and Treatment" by Steve Austin and Cathy Hitchcock.