Breast Cancer: A Puzzling Plague

By Claudia Wallis

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.

CHART: NOT AVAILABLE

CREDIT: TIME Chart

[TMFONT 1 d #666666 d {Source: National Cancer Institute}]CAPTION: Incidence of breast cancer per 100,000 U.S. women

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CREDIT: TIME Diagrams by Joe Lertola

[TMFONT 1 d #666666 d {Source: American Cancer Society}]CAPTION: HOW THE RISK SHAPES UP

WHERE CANCER IS MOST LIKELY TO BE FOUND

CHART: NOT AVAILABLE

CREDIT: TIME Chart

[TMFONT 1 d #666666 d {Source: Journal of the National Cancer Institute}]CAPTION: DANGER IN THE DIET

With reporting by J. Madeleine Nash/Chicago and James Willwerth/Los Angeles