CANCER PREVENTION OR DRUG PROMOTION?

Journalists Mishandle The Tamoxifen Story

Nature vs. nurture: The ancient argument has raged more furiously than
ever over the last, DNA-obsessed decade.

When it comes to cancer, however, scientists and journalists alike
seem to have already decided that the fault lies not in our stars - or
in the toxins clouding our night skies - but in ourselves. Case in
point: coverage of the Food and Drug Administration's October approval
of tamoxifen as a breast cancer "prevention" drug.

Tamoxifen had been tested for an average of four years on some 13,000
American women over 35. They were healthy, but defined as at high risk
for breast cancer. In the mainstream press, nary a voice was raised to
challenge the experimenters' basic assumption that age, heredity and
other unalterable facts are the only measurable cancer risk factors.
Although the American Cancer Society has estimated that 75 percent of
all cancers are of unknown origin - presumably related to some-thing
in the patients' environment - this assumption has locked scientists
into a "treatment mindset." Legitimate (read: well-funded)
researchers, along with the reporters who regurgitate their studies,
ignore environmentalists' efforts to stop cancer before it starts
(Mother Jones, 5/94) - even when, as in the case of tamoxifen, the
company offering to treat the disease may also be selling part of its
chemical cause, potentially carcinogenic pesticides.

The remaining 25 percent of breast cancers have been attributed to a
combination of genetic make-up and lifestyle factors such as
estrogenic drugs (birth control and hormone replacement pills). The
solution, according to tamoxifen manufacturer Zeneca Group PLC and the
National Cancer Institute (NCI), was another pill: the so-called
"designer estrogen" tamoxifen, trade name Nolvadex.

Most media couldn't have agreed more: "The news that a simple pill can
prevent breast cancer . . . may be the most dramatic victory against
cancer since America declared war on the disease a quarter-century
ago, experts said," burbled the Detroit News (4/7/98). The $68
million, NCI-sponsored Breast Cancer Prevention Trial (BCPT) of
Nolvadex had been halted, "so that all women in the trial . . . could
be given the chance to use tamoxifen," explained the News reporters,
adding helpfully that although the FDA had not yet approved tamoxifen
for prophylactic use, "it's already on the market, [so] doctors
immediately can prescribe it."

Playing with numbers The News writers failed to mention until
para-graph 12 that women on tamoxifen run a "slight" risk of fatal
blood clots and uterine cancer. Other reports described the danger to
women as "small" (New York Times, 4/8/98), or as no higher than that
of hormone replacement therapy (Pittsburgh Post-Gazette, 9/1 5/98;
U.S. News & World Report, 4/20/98).

The "slight" health risks found in the BCPT included a 150 percent
jump (300 percent in women over 50) in cases of uterine cancer, plus a
threefold increase in pulmonary embolisms (blood clots in the lung),
and a 60 percent rise in deep vein thrombosis (clots in major veins).
Three women taking tamoxifrn died from pulmonary blood clots.

A few journalists went for the silver lining, breezily assuring us
(Detroit News, 4/7/98) that uterine cancer is "much easier to detect
and treat" (after the minor inconvenience of a hysterectomy). Even
reporters who detailed the dark side of Zeneca's wonder drug tended to
juxtapose its dramatic 49 percent reduction in breast cancer rates
with less impressive raw numbers, not percentages, when they got
around to side effects (Denver Post, 4/6/98; Wall Street Journal,
10/30/98). As Montreal Gazette commentator Sharon Batt asked
(4/21/98), if the trial results were reported accurately as reducing
each participant's breast cancer risk in absolute terms by about 1
percent (from 2 percent to 1 percent), how many women would be lining
up for a tamoxifen fix?

And how many have already done so, due to reports that ignored the
trial's failure to demonstrate any decrease in mortality or other
long-term benefits? Almost without exception, reporters agreed that
the BCPT proved the drug can reduce a woman 5 chances of getting
cancer-period. Not so: Women taking tamoxifen had fewer breast cancers
during the trial only. Other studies have shown mixed or negative
results with more than five years of tamoxifen use. And the BCPT
itself, according to testimony at FDA hearings, showed that
participants who stopped taking tamoxifen developed breast cancer more
frequently than trial participants on a placebo.

Nor did most writers - including the author of a June 1998 column in
Ebony magazine - notice that Arican-Americans and other minority
groups were grossly underrepresented in the BCPT; 94 percent of the
13,388 participants were white. Only one newspaper story found in the
Nexis database (LA. Times, 10/26/98) noted that trial scientists
admitted their study "did not include enough nonwhite women to know
whether the effect is similar for women of all races." In fact,
according to researchers' testimony before the FDA, twice as many
women of color developed breast cancer on tamoxifen as on a placebo.

Creative truths There are lies, damn lies and medical study results.
But how did health pundit Jane E. Brody come away with the impression
that tamoxifen "offers women... reduced risk of cardiovascular
disease" (New York Times, 9/8/98) - a hypothesis specifically refuted
by the BCPT results Journal of the National Cancer Institute
(9/16/98)? In the same column, Brody states boldly that raloxifene,
the new kid on the designer estrogen block, "does not stimulate
uterine cell growth." Brody apparently based her endorsement on a
couple of brief osteoporosis studies; experts regard the results as
promising but inconclusive. (Brody did not return a call for comment.)

A more popular example of misinformation has been the claim that
life-threatening tamoxifen side effects don't appear in women under
50, and "thus the benefits most clearly outweigh the risks for younger
women," as the New York Times editorial board announced April 8.
According to official BCPT results, however, increased risk of uterine
cancer and blood clots merely occurred "predominantly" and "more
frequently" in women over 49. This difference in interpretation could
be critical for a healthy 35-year-old with future plans for her uterus.

Oddly enough, one such offender was Prevention magazine (10/1/98),
published by Rodale Press, a long-time advocate of organic
agriculture. After interviewing five sources-four directly involved in
the BCPT-the freelance writer chose to ask not, "Why are tax-payers
funding a study to benefit Zeneca, manufacturer of suspected
car-cinogenic pesticides like acetachlor?," but, "In the future, will
every woman take an anti-breast-cancer pill along with their daily
vitamin?"

The company's iconoclastic founder, Robert Rodale, must be gyrating in
his grave. (A promised return call from Prevention's research director
never materialized.) Reporters need not shoulder all the blame;
government and industry have been pushing their own creative
variations of the truth. For instance, the Johns Hopkins-run web site
on tamoxifen refers to uterine cancer as "a relatively small price to
pay" for tamoxifen protection; an October 21 NCI news release states
that "women under 50 appeared to suffer no adverse effects"; a camera
ready" article distributed by a Manhattan PR firm under contract with
Zeneca claims all cases of stroke, blood clots and uterine cancer were
detected at a very early stage and were readily treatable."

Unscientific methods Nothing, however, excuses our profession's
collective amnesia. Moldering in newspaper morgues are accounts of the
suspension of recruitment into the BCPT and the removal of its head,
Dr. Bernard Fisher, due to proof of fraud at a major test center,
failure to conduct onsite evaluations, and delays in reportng possible
uterine cancer fatalities in a precursor to the BCPT. Until Congress
intervened, many women signed trial consent forms that lacked an
accurate risk assessment; the forms included a false statement that no
uterine cancer deaths had occurred (San Francisco Chronicle, 3/16/94;
Ladies' Home Journal, 2/95).

After the brouhaha died down, the NCI and the rehabilitated Dr. Fisher
needed a victory - or so an alert reporter might have inferred when
the institute announced its triumphant early halt to the BCPT last
April, saying that the benefits of tamoxifen were so clear that those
on the placebo should have the opportunity to begin taking the drug.
Who noticed that participants who had stopped taking tamoxifen had
begun to develop more cases of breast cancer than the placebo group?
Why did the NCT preclude long-term evaluation by encouraging the
placebo group to join a new drug trial? Where were the skeptics?

Not in the U.S. media, where headlines such as "Breast Cancer Trial
Offers Hope to 20,000 Women" (USA Today, 10/22/98) greeted news of the
NCI's plans for a new tamoxifen/raloxifene trial. But in Europe
researchers cooperating with the institute were dismayed by the
unilateral disarmament of the BCPT. A few U.S. articles mentioned that
major tamoxifen trials in Britain and ltaly released results in July
that showed no reduction in cancer risk (e.g., Wall Street Journal,
7/10/98). Unlike the NCI's results, the European researchers published
the preliminary results of their studies in a peer-reviewed journal,
The Lancet (7/11/98).

The European studies should have been hot news - except that the NCI
bandwagon had a head start. By October, the troublesome past had been
largely forgotten (compare Time's somewhat critical review of
tamoxifen April 20 and its November 9 "how to get it" advice).

Susan Okie of the Washington Post (9/3/98) was among the few who got
the real story: Bucking heavy pressure, the FDA refused to say
tamoxifen prevents cancer. Zeneca can advertise its product only for
the "short-term reduction of risk." (The decision will still allow
Zeneca to pitch the drug directly to consumers; the company estimates
its potential new U.S. market at 29 million women.)

Okie caught a glimpse of the real "scientific method," a bare-knuckled
brawl over millions in sales and grants. It's time journalists on the
cancer beat followed her - and the money - behind the laboratory
doors. As one investment analyst, commenting on breast cancer
treatment drugs, told New York Times business writer David J. Morrow,
"You could say that drugs for this category will always be a growth
industry."