A Travesty, at Women's Expense

 L.A. Times, June 22, 1992

Thousands are to be given a chemotherapy drug as a breast cancer preventive, despite evidence of deadly side effects.

The government's National Cancer Institute this spring launched a large-scale breast-cancer prevention trial, recruiting thousands of healthy women at increased risk of breast cancer -- including those with close relatives with the disease and also anyone over 60. Half are to be treated with tamoxifen, a potent chemotherapy drug; the remainder will get a placebo. The NCI believes tamoxifen can reduce breast cancers by 30%, while also reducing heart attacks and preventing osteoporosis.

With one in nine women expected to develop breast cancer over a lifetime, the trial would seem worthy of unqualified support. However, the evidence that tamoxifen can prevent breast cancer is largely wishful thinking. To make matters worse, the risks to healthy women of a wide range of serious complications, including uterine cancer, fatal liver cancer, liver failure, life-threatening blood clots and crippling menopausal symptoms are unacceptable. This trial must be halted in its tracks.

The NCI's rationale is that tamoxifen, which is modestly successful in treating breast cancer, appears to reduce the risk of new cancers of the other breast. This benefit has only been seen in some patients in about half of the studies that have been done. The protection also appears largely restricted to post-menopausal women. However, the NCI ignores this and misleadingly offers healthy younger women the hope of prevention.

In addition, Swedish studies suggest that tamoxifen increases mortality in post-menopausal women who do develop cancer in the other breast during treatment; these cancers were highly aggressive and treatment-resistant. This evidence appears confirmed by studies showing that while tamoxifen reduces breast cancer in rats, cancers that do develop are highly malignant. There are also questions concerning whether heart benefits actually exist, and to what extent.

If tamoxifen's effectiveness were the only question, our alarm would not be so great. But the drug is implicated in a range of serious and sometimes life-threatening complications, although the NCI dismisses these as "infrequently severe."

Tamoxifen triples the risk of uterine cancer, even in patients followed for relatively short periods. Reaching a new low in medical sexism, statistician Richard Peto, a leading British supporter of the trial, dismisses the risk as "no big deal," since uterine cancer is curable by hysterectomy.

Tamoxifen is also a "rip-roaring liver carcinogen," according to Gary Williams, medical director of the American Health Foundation, inducing aggressive cancers in 100% of rats at high doses and 20% at lower doses equivalent to those being used in the prevention trial. This is acknowledged by the drug's manufacturer. ICI Americas, Inc. The prestigious British Medical Research Council warns of the absence of any safety margin at the trial dose. Yet the NCI misleadingly trivializes evidence of liver cancer in rats and ignores reports of two liver cancers in women just double the dose used in the trials.

Tamoxifen also promotes liver cancer in rats previously exposed to low doses of other carcinogens.

Moreover, as the British council emphasized, "Few women have received tamoxifen for longer than five to seven years, whereas the maximum incidence of liver tumors induced by known carcinogens occurs at eight to 10 years." Indeed, it is probable that a significant number of healthy women receiving tamoxifen may die from liver cancer after a decade or so.

Recent Swedish data suggest a more than 50% increase in new cancers, including gastrointestinal, among breast cancer patients treated with tamoxifen.

Shortly before the NCI started its trial, the blue-ribbon British Committee on Safety of Medicines reported five cases of liver failure with four fatalities, five hepatitis with one fatality and 11 other liver complications in breast-cancer patients treated with tamoxifen. Previously undisclosed similar evidence has just been obtained from the U.S. Food and Drug Administration.

The NCI recognizes a six-fold risk of often-fatal blood-clotting problems with tamoxifen, but the trial's coordinator suggests, with no supporting evidence, that this is due not to tamoxifen itself, but to "the interactive effect of [other] chemotherapy." Sometimes-severe menopausal symptoms, including hot flashes and vaginal discharge, are other recognized complications that the NCI seeks to downplay.

Incredibly, the NCI claims that theirs is "one of the most comprehensive informed- consents we've ever seen." The consent form exaggerates tamoxifen's possible and questionable benefits and trivializes probable and high risks. These concerns have stimulated a congressional inquiry led by Rep. Ted Weiss (D-N.Y.). The consent form's waiver of compensation for illness and injury, which participants must sign, is unlikely to protect the NCI or its investigators and hundreds of U.S. and Canadian centers and institutions involved in the trial from a future flood of malpractice and punitive claims for cancer and other complications. The doctrine of informed consent is legally protective only when all facts relevant to benefits and risks are fully and affirmatively disclosed.

The use of women as guinea pigs is familiar. There is reealing consistency between the tamoxifen trial and the 1970s trial by the NCI and American Cancer Society involving high-dose mammography of some 300,000 women. Not only is there little evidence of effectiveness of mammography in premenopausal women, despite NCI's assurances, no warnings were given of the known high risks of breast cancer from the excessive X-ray doses then used. There has been no investigation of the incidence of breast cancer in these high-risk women. Of related concern is the NCI's continuing insistence on pre-menopausal mammorgraphy, in spite of contrary warnings by the American College of Physicians and the Canadian Breast Cancer Task force, and in spite of persisting questions about hazards even at current low-dose exposures. These problems are compounded by the NCI's failure to explore safe alternatives, especially transillumination with infrared light scanning.

Meanwhile, the NCI ignores other preventable causes of breast cancer, particularly fat contamination with pesticides and other carcinogens. It recently canceled a proposed $100-million study on dietary fat in favor of the tamoxifen trial.

The tamoxifen project is a travesty of science and a parody of cancer prevention. It also strikingly illustrates fundamental problems with federal cancer policies. The NCI suffers from a mindset myopically fixated on diagnosis, treatment and basic research, with relative indifference to cancer prevention.

Drastic reforms of NCI priorities and policies are essential to curbing the cancer epidemic, including escalating breast cancer rates. Only congressional action and strong support by women's and other concerned citizen groups can make this come about.