Lower Tamoxifen Dosage May Be Healthier
Mon Jun 23, 03

By LAURAN NEERGAARD, AP Medical Writer

WASHINGTON - Tamoxifen is the top choice of doctors worldwide for preventing breast cancer from coming back — and, in high-risk women, for keeping it from striking in the first place.

Yet the drug causes some lifethreatening side effects, and now scientists wonder if dramatically lowering the dose could give women the benefits with fewer risks.

There is some tantalizing new evidence, albeit preliminary, that suggests it might. The question is how to prove it: Who would dare test a lower dose instead of the proven one? Besides, most U.S. research involves testing newer, more expensive alternatives in the quest for a next-generation tamoxifen.

But a small group of scientists in several countries hopes to revamp tamoxifen, citing the appeal of a time-tested medicine available in cheaper generic form.

"In many underdeveloped countries, being able to give a cheap, safe medicine to cut your risk of breast cancer in half for pennies — this has such a worldwide impact," says Dr. V. Craig Jordan of Northwestern University, who developed the drug 30 years ago.

Tamoxifen is a multiple-personality drug: It acts like the estrogen hormone in some tissues and like an anti-estrogen in others.

In women with estrogen-sensitive breast cancer, it fends off cancer by blocking estrogen's growth-spurring effects. For the same reason, women at high risk of developing breast cancer can cut that risk by 44 percent if they take tamoxifen pills daily.

But tamoxifen acts like estrogen in the uterus and bloodstream, doubling users' risk of getting uterine cancer and tripling the risk of a potentially fatal blood clot.

When tamoxifen first debuted, it was hailed for having none of chemotherapy's immediate toxic effects — so few questioned if the daily dose of 20 milligrams was too high until several years ago, when thousands of still-healthy women started taking it for cancer prevention.

"Drugs have often been marketed at what were later recognized as excessive doses," notes Dr. Andrea Decensi of the European Institute of Oncology in Milan, Italy, who is leading the safer-dose hunt. "Our results suggest that tamoxifen does not escape this rule."

Decensi gave 120 women with breast cancer either the standard 20 mg of tamoxifen or radically lower doses — 5 mg or 1 mg — for four weeks before tumor-removing surgery.

A key measure of cancer cell growth showed decreases of the same amount, 15 percent, regardless of tamoxifen dose, Decensi reported in the Journal of the National Cancer Institute this month. Regarding side effects, women taking less tamoxifen also had lower levels of key clotting substances in their blood.

A similar study from Brazil, published in the European Journal of Cancer and co-authored by Jordan, also found low-dose tamoxifen can stop cell growth.

Decensi has begun additional studies of whether lower-dose tamoxifen is safer for the uterus.

The preliminary research is intriguing, but no woman should lower her tamoxifen dose unless and until far larger and stricter studies prove that really works, cautions Dr. Powel Brown of Houston's Baylor College of Medicine.

For many scientists, the emphasis is on finding a tamoxifen alternative:

Some 16,000 women are taking either tamoxifen or another estrogen-modifying drug, raloxifene, to see if they prevent breast cancer equally well. Raloxifene today is sold to treat osteoporosis, but seems to block estrogen's breast effects like tamoxifen does. Although it has its own side effects, including questions about blood clots, it doesn't seem to cause uterine cancer. Results of the research are due in a few years.

A new family of drugs, called aromatase inhibitors, are challenging tamoxifen for treatment of late-stage breast cancer. A study in Europe recently was begun to see whether they might work as well or better than tamoxifen for preventing cancer, too; similar research is planned here. But aromatase inhibitors can be used only by postmenopausal women and can increase the risk of bone-thinning osteoporosis, drawbacks tamoxifen doesn't have, Brown notes.

"These are all pieces of a jigsaw," says Jordan, who wants equal interest in researching cheaper, low-dose tamoxifen.

A note from Dr. Moore: Your health is not a “jigsaw” puzzle that needs to be put together. I am astounded by the inability of the conventional medical/industrial complex to not use humans as test experiments for their pharmaceuticals. This is yet another chink in the armor of this toxic drug. There are plenty of treatment options available: our “Indolplex” a bioavailable formulation of diindolylmethane (DIM), an indole phytonutrient found in cruciferous vegetables has been shown to shift the balance of circulating estradiol and estrone to safer metabolites, preventing dysestrogenism. Best of all it is free of side effects and completely safe. Also, our “Resolve (Upper) “ concentrated herbal extract product is an excellent product for persons with this type of medical history or risk factors.