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.
