TIME: Almanac 1993/TIME Almanac 1993.iso/time/011491/0114350.000

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                #┤                                                          MEDICINE, Page 48

COVER STORIES

A Puzzling Plague


What is it about the American way of life that causes breast
cancer?

By CLAUDIA WALLIS -- Reported by J. Madeleine Nash/Chicago and
James Willwerth/Los Angeles


    In the bad old days, some 20 years ago, no one had the heart
even to talk about it. Breast cancer struck the most evident
of a woman's assets, where the motherly and the erotic are
joined. And treatment of the disease was a nightmare of pain,
disfigurement and uncertainty too terrifying to contemplate.
A seemingly healthy woman with nothing more than a tiny lump
in her breast (and a larger one forming in her throat) could
agree to have a biopsy performed and not know whether she would
awake from surgery with a small bandage on her breast -- or no
breast at all.

    Much has changed since then. For one thing, breast cancer
is widely discussed. Celebrity after celebrity -- a veritable
Breast Cancer Hall of Fame -- has stepped forward to demystify
the disease and soften its stigma, beginning with Shirley
Temple Black, Ingrid Bergman and Betty Ford, and more recently
including Nancy Reagan and Gloria Steinem. Lessons on cancer
detection and the importance of mammograms are the subject of
elaborate public information campaigns.

    More important, the surgical and post-surgical options have
multiplied. Chastened by better educated and more demanding
patients, doctors now wait after a positive biopsy to discuss
these options before moving in to amputate. Just last year a
consensus meeting convened by the National Institutes of Health
formally recommended lumpectomy, the removal of a cancerous
lump plus a small amount of surrounding tissue, followed by
radiation therapy, as an equally effective alternative to
breast removal in many cases. And the success rate for treatment
is up -- not dramatically, but up. Nowadays, 76.6% of
breast-cancer patients survive five years after surgery, and
63% are alive 10 or more years later. In 1970 the five-year
survival rate was 68%.

    But there is also bad news about breast cancer. The number
of cases continues to soar. According to the National Cancer
Institute (NCI), the U.S. incidence increased 32% between 1982
and 1987. Only lung cancer is rising faster. Cancer is the
leading cause of death for women 35 to 50, and breast cancer
is the most common malignancy in this age group. All in all,
an American woman has a 1-in-10 chance of developing breast
cancer over the course of her lifetime, and that risk keeps on
rising.

    The big question is why. Most experts on the disease agree
that part of the increase can be attributed to earlier
detection of tumors. Some 65% of American women over 40 have
had a mammogram, up from about 20% in 1979. The widespread use
of this tool, a low-dose X ray of the breasts, has meant that
more women are discovering their tumors in the early stages,
before a lump can be felt. In past decades, prior to the spread
of mammography, such women might have died of other causes
before their breast cancer was diagnosed.

    Nonetheless, most investigators of the epidemic believe
early detection is only part of the story. They look at the
fact that breast cancer is far less common in other parts of
the world and conclude, ominously, that the answer lies in some
facet of the American life-style. "Something in our environment
is contributing," contends Dr. Marc Lippman of Georgetown
University.

    Study after study has explored the possibilities. Could it
be the birth control pill? Probably not, since dozens of
investigations into that question have produced a quagmire of
contradictions. How about smoking? Again, there is no clear
connection. Alcohol? Drinking seems to raise the risk of the
disease slightly, but the association is too weak to account
for America's prodigious rate. What about the widespread use
of estrogen therapy following menopause? Studies show only a
mildly elevated risk. And while food additives and even lack
of sunlight have come under suspicion, there is little evidence
to convict them.


    THE FAT FACTOR

    Instead, many researchers around the world are pointing to
another component of the Western way of life: a diet rich in
fat. Researchers have known for more than 40 years that
high-fat diets promote the growth of mammary tumors in
laboratory animals. They have also observed that the varying
rates of breast cancer in various countries correlate neatly
with the amount of fat in a nation's diet. The U.S., Britain
and the Netherlands, which have some of the world's richest
diets, also have among the highest breast-cancer rates.
Meanwhile, in countries such as Japan, Singapore and Romania,
where the diet is very lean, the incidence of breast cancer is
one-sixth to one-half the U.S. rate.

    On the theory that genetic factors might be responsible for
such national variations, researchers have looked at immigrant
groups. They have found that when Japanese move to the U.S.,
or Italians to Australia, their previously low breast-cancer
mortality rate rises to match the higher rate of their adopted
country within a generation or two, as diet and life-style
change. "The results are too consistent to believe that the
association is indirect," says Maureen Henderson, an
epidemiologist at the Fred Hutchinson Cancer Research Center in
Seattle. When it comes to the breast cancer-fat connection,
she says flatly, "I'm sure of it."

    Japanese researchers are also convinced. Breast cancer is
one of the fastest-growing diseases among Japanese women, with
the incidence up 58% between 1975 and 1985. "The largest factor
behind the sharp rise is the Westernization of eating habits,"
says Dr. Akira Eboshida, chief deputy director of the Health
and Welfare Ministry's Disease Control Division. "We are eating
more animal fat and less fiber." Cancer of the breast is not
the only ailment rising with the larding of the Japanese diet.
Heart disease is also surging, as is cancer of the colon,
ovaries and prostate. All have been linked to a high-fat diet.
On the other hand, stomach cancer, historically the most common
cancer in Japan, is falling as the nation moves away from its
traditional diet of salty, pickled and smoked foods. "If the
current trend continues," predicts Eboshida, "breast cancer
will replace stomach cancer as the No. 1 killer of Japanese
women in the next century."

    Despite such evidence, not everyone shares the conviction
that fat is the villain. Critics of this theory point out that
statistical correlations are not the same as proving cause and
effect. Many researchers argue that there are probably several
life-style factors rather than a single culprit. "The high
rates are not due to one bad habit, but to our whole way of
life," says Mary-Claire King, a cancer geneticist at the
University of California, Berkeley.

    According to Dr. Walter Willett at the Harvard School of
Public Health, overall calories may play a larger role than
fat: Americans may simply be eating too well. Willett points
out that breast-cancer rates tend to be highest in prosperous
countries where people are well nourished. In such lands of
plenty, girls begin to menstruate at an earlier age, women tend
to have their children later in life and menopause also comes
later. Late menopause (after 50), delayed childbearing (after
30) and early onset of menstruation (before 12) are all
acknowledged "risk factors" for breast cancer. For older women,
obesity also increases the risk of the disease. King notes that
better education and job opportunities for women have furthered
the trend toward postponed motherhood and childlessness (also
a risk factor). "All the things that cause women to be healthy,
well-educated and have careers put them at risk for breast
cancer."

    Critics of the fat theory also point to several studies that
seem to refute it, including a survey by Willett of 90,000
nurses from 34 to 59. Though the diets ranged from 32% fat
content to about 44% (the U.S. average is 42%), the Harvard
researcher could find no correlation between fat intake and the
incidence of breast tumors. One problem with Willett's study:
many researchers believe that dietary fat must be more
radically reduced, to about 20% of total calories, to affect
the occurrence of breast cancer.

    The proof, of course, is in the pudding, or in this case,
not eating any. Unfortunately, researchers seeking conclusive
evidence of the effects of a very low-fat diet have had little
success in obtaining funds. One concern is cost. Another is
that women participating in such trials would have trouble
adhering to the drastic regimen, which would mean very limited
amounts of meat, dairy products and oils of any kind.

    To show that it can be done, Henderson in Seattle completed
a three-year pilot study, funded by the National Institutes of
Health, of 2,000 postmenopausal women who were painstakingly
taught how to follow a 20% fat diet. "We give them a Ph.D. in
fat," she explains. Her hope was that the pilot would lead to
NIH funding of a 10-year effort with 24,000 women. No such
luck. A competing proposal for a similar study that would cost
$107 million was on the verge of being financed  when an NCI
advisory panel decided last month to put it on hold -- a
crushing disappointment for many researchers.


    THE ESTROGEN CONNECTION

    If fat does figure in the development of breast cancer, just
what role does it play? No one in the research community
believes that too many thick shakes and fries can in themselves
cause normal, well-behaved cells to mutate into unruly
malignant ones. In fact, no one has the faintest notion what
causes the initial genetic changes to occur. "In lung cancer
we have a reasonable idea that the major cause is cigarette
smoking," says Dr. Philip Leder, chairman of Harvard's
department of genetics. "In skin cancer we understand that the
major cause is ultraviolet light, which is absorbed by DNA and
causes it to break. But with breast cancer we don't have any
idea what the precipitating factors are."

    Doctors have long been convinced that some people are
genetically predisposed to develop breast cancer. A woman whose
mother or sister had the disease before menopause has five to
six times the usual risk of developing it. If either one had
the disease in both breasts, then the woman's risk is five to
10 times the norm.

    Though scientists do not know how breast cancer begins, they
do have some ideas about how it progresses. The female hormone
estrogen, which is produced in the ovaries and causes a young
girl's breasts to develop, also plays an unmistakable role in
promoting the growth of tumor cells. Why do childlessness, late
menopause, early onset of menstruation and delayed childbearing
all increase the risk of breast cancer? One likely explanation
is that all involve a prolonged, uninterrupted presence of high
levels of estrogen in the bloodstream. Doctors have also
noticed that women whose ovaries were removed before age 40
rarely get breast cancer.

    Researchers focusing on the role of fat in the development
of cancer have been particularly intrigued by the estrogen
connection. Biologists have long known that estrogen is
produced not only in the ovaries but also in fat cells. Obese
women have higher levels of estrogen than thin ones -- a
probable factor in their greater risk of breast cancer after
menopause.

    But it has been only in the past five years that researchers
have found a link between estrogen levels and fat in the diet.
Women who eat lots of hamburgers, thick shakes and other fatty
foods have higher overall levels of estrogen and especially
large amounts of the "biologically active" form. Equally
significant, endocrinologist David Rose of the Naylor Dana
Institute in Valhalla, N.Y., has found that when women switch
to a very low-fat diet (20% of total calories), their estrogen
levels quickly drop by 20%. Advocates of the dietary-fat theory
regard this observation as a crucial bit of supporting evidence.
Given estrogen's established role in promoting breast cancer,
the fact that fatty foods directly affect estrogen levels means
that, as Maureen Henderson puts it, "it's biologically rational
that fat can influence cancer."

    Considering all the fuss over fish oil and polyunsaturates
in the world of heart disease, one might wonder if the type of
fat consumed makes any difference. "The data are very confusing
on this," admits Rose. Some researchers believe that certain
fats are more villainous than others with respect to cancer,
but Henderson and others say all fat should be reduced.
Drastically.


    THE MAMMOGRAM MUDDLE

    Until the government decides to fund a long-term dietary
study and until the work is completed, the value of an
ultralow-fat diet in preventing breast cancer will remain open
to question. For women 40 or older, however, there is one bit
of medical counsel that has almost unanimous approval: Get a
mammogram. Now. And do it regularly.

    Consider these facts. By the time a breast tumor is large
enough to be felt as a lump, it is generally more than 1 cm
(0.4 in.) in  diameter and contains several billion cancer
cells, some of which may have broken loose, circulated through
the bloodstream and begun to infiltrate other organs. A
mammogram can detect pinpoint tumors that are less than 0.5 cm
(0.2 in.) across, often well before the  process of metastasis
has started. This is not to say that a manual exam by a doctor
or the woman herself is a waste of time. Such exams can
sometimes turn up tumors missed by X rays. But the
early-detection capability of mammography clearly saves lives.
A 1987 study found that for women whose tumors were discovered
early by mammograms, the five-year survival rate was about 82%,
as opposed to 60% for a control group.

    And if that is not incentive enough, early detection through
mammography can sometimes bring another bonus: surgery that
spares the breast. A small, early tumor can often be removed
with a lumpectomy procedure rather than a mastectomy.

    Why, then, aren't American women running en masse to the
mammographer's office? Why do less than a third of women over
40 have mammograms every one to two years, as experts
recommend? One reason may be lingering fears about radiation
exposure. Nowadays, however, mammography doses are about
one-tenth of what they were 20 years ago -- less than one
receives from cosmic rays on an airplane flight. A more
significant factor, says Dr. Sarah Fox, a UCLA professor of
family medicine, is "that physicians aren't making the
recommendations." Doctors often feel that mammograms are
unnecessary for women who are not in a high-risk category.
"Sometimes they'll say, `You've had a couple of children and
you've got no family history, so relax,'" explains Dr. Robert
Smith of the Centers for Disease Control in Atlanta. Yet three
out of four breast-cancer victims have no known risk factors,
says Smith. No woman over 40 should consider herself safe. And
certainly her doctor should know better.

    The cost of mammograms may also discourage women. Insurance
frequently fails to cover the $50 to $200 procedure. Medicare
just began paying for it this year. Public hospitals do not
always offer such screening, and some state Medicaid programs
have refused to provide reimbursements, which helps explain why
breast cancer is often diagnosed too late among the poor. For
black women in particular, the five-year survival rate is only
64%, in contrast to 77% for white women.

    Adding to the confusion on mammography is the unfortunate
fact that medicine's powerful professional societies cannot
agree on what to recommend. The American Cancer Society urges
a mammogram every one or two years for women between ages 40
and 49, and annually thereafter. The American College of
Physicians disagrees, claiming that a mammogram is not
"cost-effective" for women under 50, since only 20% of
malignancies occur in these women.

    As if matters were not muddled enough, a storm has erupted
in recent years over the uneven quality and accuracy of
mammograms around the U.S. "Half the states do not have a
licensing procedure for radiologic technologists. It could be
the office receptionist pushing those buttons," warns Marie
Zinninger, a quality-control specialist for the American
College of Radiology. Another problem, according to the
National Cancer Institute, is that General Electric, Philips
and other manufacturers have flooded the market with mammography
machines. Many wind up in the offices of doctors who lack the
proper training in the use and maintenance of these machines.
The College of Radiology has responded with a drive, launched
in 1989, to examine and certify mammography facilities. It
advises patients to choose a high-volume accredited facility.
Another sign that a mammogram is up to snuff: the ouch factor.
To get a good picture, the mammography machine must compress
the breast. "If you're not uncomfortable," says UCLA's Fox,
"you're probably getting a bad mammogram."


    A POLITICAL SOLUTION?

    In recent years a ground swell of breast-cancer victims,
feminists and legislators, inspired by the success of the AIDS
lobby in bringing attention and funds to that epidemic, have
been pushing for better regulation of mammography standards,
for mandatory insurance coverage of mammograms, and generally
for more research into the still mysterious roots of breast
cancer. They point out that the U.S. government spends only $77
million a year investigating ways to prevent the illness,
against $648 billion on heart-disease prevention. Last week
Congresswoman Mary Rose Oakar of Ohio sought to redress the
shortfall by introducing a bill that would add $25 million to
the NIH budget expressly for basic research on breast cancer.
Meanwhile the National Women's Health Network, a lobbying group
in Washington, continues to press for federal funding of
studies on the effects of diet.

    But given the demands on the limited federal research
budget, such efforts will probably fail. Perhaps as
unfortunate, notes Dr. Geoffrey Howe, a leading researcher on
cancer and diet at the University of Toronto, is the fact that
"political pressure is the criterion for deciding what
scientific research needs to be done."

    For patients, the lack of answers and of resources to find
them amounts to an all too literal deadlock. "I am scheduled
to die because I have metastatic breast cancer," says Elenore
Pred, founder of the Breast Cancer Action group in San
Francisco. "I'm part of the 44,000 women for whom there is no
cure. But I refuse to be written off." Pred is devoting her
days to lobbying for more research and better public education
on the disease. As the mother of two daughters, she could leave
them no healthier legacy.


____________________________________________________________
DANGER IN THE DIET

                                         Breast-Cancer
                       Fat Intake*           rate**

    Japan                  23%                42.2
    Romania                23%                95.7
    Israel                 32%               165.9
    Britain                38%               173.2
    France                 39%               166.1
    Switzerland            41%               207.6
    U.S.                   42%               231.7


*  estimated proportion of total calories. ** annual incidence
per 100,000 women ages 45-69.