The American woman has one chance in 11 of getting breast cancer. If her mother had it, her chances are almost one in five. If she waits until after she is 30 to have her first child, the risk is even higher. And the danger may be increased even more by her life style as a teen-ager.
There have been dramatic improvements in the practice of medicine over the last 50 years, but the death rate for breast cancer is the same today as it was in 1930. Since 1965, the number of reported cases has risen by 50 percent.
Those are the cold statistics. They explain not only why breast cancer is so feared by every woman, but also why doctors and researchers have been forced to reexamine their entire concept of how and why this disease develops and persists.
That reexamination has led many of the nation's cancer reseachers to focus on the environment in their search for causes of the disease.
Radiation, the American diet, hormones and viruses have been implicated as agents that may plant the earliest seed s of the cancer, which begins as a tiny clump of misguided cells buried in the fatty breast and later spreads to the brain, liver, lungs and other vital organs. These environmental factors, many of the researchers said, are of special concern during the periods when a woman is most vulnerable: adolescence and menopause.
The environmental theory is a source of despair and hope for the cancer researchers and physicians. Some noted that it raises grave questions about how health is impaired by the modern American environment.But it also implies that the disease can be controlled if the conditions of life are changed. As Harvard epidemiologist Dr. Philip Cole put it: The vast majority of breast cancer "is conditioned by environmental factors, and is thus potentially preventable."
Breast cancer now is seen by several scientists as a process that begins as many as 20 years before a tumor becomes detectable. It starts, these scientists believe, during the critical years at both ends of a woman's reproductive life, when environmental factors interact with the genes to produce a spectrum of disease.
This concept originated with reports in the late 1960s of breast cancer in women who were exposed many years earlier to radiation; some who were survivors of the atom bomb in Japan, others who were given highdose x-rays during treatment of tuberculosis.
The tests showed a clear pattern. Scientists found that the number of breast cancer cases increased in women exposed during the teen-age years and in women irradiated after age 50. But there was no cancer increase in women between the ages of 30 and 50.
A second clue to the mystery of breast cancer was provided by studies of female hormones.
Scientists had known for many years that women who had an early first pregnancy had a lower risk of getting the disease, while women who had their first pregnancy after age 30 ahad an increased risk. They also knew that early puberty and late menopause increased the chances of getting the cancer. Since a woman's hormone balances changes during those two periods of her life, researchers deduced that homonal balance might determine the risk.
Using those concepts as a starting point, they studied the different forms of estrogen -- the major hormone secreted during the reproductive years -- in women of different nationalities. They found that women produce at least three forms of estrogen -- one predominant in populations with a low risk of breast cancer, and another more common in high-risk populations.
The cancer researchers then measured the estrogen balance -- known as the estriol ratio -- in Asian and American women. They discovered that Asian women have a high estriol ratio and a low risk of breast cancer, while American women have a low estriol ratio and a high risk of getting the disease. Of equal interest, they found that Asian women living in Hawaii have an intermediate ratio and an intermediate risk.
From this, Harvard's Cole concluded that a change in environment -- perhaps in diet, above all -- affected the hormonal balance of the Asian immigrants in Americanized Hawaii and thus increased their chances of getting breast cancer.
A third clue in the mystery came with the advent of mammography, an x-ray technique which provides a picture of the breast ducts and glands.
A mammographer, J.N. Wolfe, observed from his work that there were four or five patterns of breast tissue, ranging from fine, thread-like, unbeaded ducts and nodular glands. In 1976, Wolfe discovered that the fine pattern brings the lowest risk of breast cancer, while the thick pattern has the highest risk.
From this it might appear logical that women with the high-risk pattern should receive mammograms frequently to detect breast cancer. But there is a paradox, as Cole pointed out: These high risk women are the same ones who he said should avoid the radiation that mammograms entail. Cole cautioned against immediate and widesspread use of Wolfe's patterns for screening, saying more studies are needed and that a screening method other than mammography might be preferable.
Still, Wolfe's patterns were of great value to other scientists who were perusing the hormonal causes of the disease. Their studies indicated that adolescents had the high-risk breast pattern, but that it usually changed at adulthood into one into one of the other, lower-risk patterns.
Piecing together these findings, UCLA hormones specialist Dr. Stanley G. Korenman proposed what he calls the "estrogen window" theory. Here is how it works:
Every woman goes through two periods in her life when the hormonal cycles are irregular -- adolescence and menopause. During those periods, which can last two to 10 years, the ovaries secrete estrogen but do not reliably produce an egg each month. Estrogen therefore may be present in the blood without being balanced by the other major female hormone, progesterone, which normally is produced after ovulation.
According to Korenman, this state of "unopposed estrogen" may leave a window open to dietary and environmental promoters of cancer.
Although Korenman's idea is untested, it would help explain why an early pregnancy could lower the risk of breast cancer by providing progesterone and regulating the menstrual cycle, thus closing the estrogen window. It also could explain why Japanese women who were in their teens or in their 50s at the time of the Hiroshima bombing had more breast cancer than other women. And if it is true, it suggests that teen-agers who take birth control pills, which close the estrogen window by providing progesterone, might decrease their breast cancer risk, while women who take estrogen drugs after menopause to combat "hot flashes" and other symptoms might increase their risk by prolonging the state of unopposed estrogen.
There is no evidence at this point that birth control pills do affect breast cancer risk, and studies of estrogen use by women after menopause are contradictory. But, as Cole points out, it may be too soon to tell. The radiation studies indicate it takes up to 20 years for environmental factors to affect breast cancer statistics.
The years between exposures to a potential carcinogen and development of breast cancer make it difficult for researchers to study the degree of risk connected to specific factors like radiation or hormones. But nutrition expert Dr. Ernest L. Wynder is convinced there already is enough evidence incriminating fat in the diet to justify experimental dietary changes in patients being treated for breast cancer.
"We always expect we have got to have all the mechanisms fully understood before we intervene," Wynder said, charging that his colleagues are too conservative in the field of prevention. He noted that many studies in the past 30 years have shown that high-fat diets hasten tumor development in animals and there is a direct correlation between the breast cancer rate in a country and the amount of fat in the local diet.
The highest incidence is in countries like the United States, where people eat large quantities of dairy products and greasy foods.
In humans and animals, fat in the diet affects the proportions of estrogen and prolactin, another hormone, in the blood, Wynder said. In rats, such hormonal alterations have been linked with breast tumors.
Using the statistics linking diet and geography, Wynder suggested that dietary fat may operate the same way in humans that it does in rats.
Reserchers like Wynder and Columbia's Sol Spiegelman, whose work has been described in the past as seeking the cause of cancer, agree that breast cancer is a disease with many contributing causes. Although Spiegelman's work connects the tumor to a virus, he is less impressed by the idea that viruses cause breast cancer than by the possibility that his virus research may lead to a test to diagnose the disease earlier.
Spiegelman and his coworkers have discovered a protein on the surface of human breast cancer cells similar to one made by a virus that causes breast tumors in mice. The protein seems to be present only on breast cancer cells and can be stained to make the cells stand out clearly under a microscope.
Doctors at several hospitals are sending Spiegelman specimens from breast cancer patients, and the researchers find they can identify minute evidence of tumor spread -- even single tumor cells -- in lymph nodes, the clumps of "guard cells" in the tissue surrounding the breast. In mice, they can diagnose breast cancer with a blood test that picks out the protein.
Although the researchers have not refined their chemical method enough to find the protein in the blood of women with breast cancer, Spiegelman says that within a year they may have a blood test that can pick up cancer sooner than current tests.
Most breast cancer cases are still diagnosed only after a patient or her doctor finds a lump while physically examining the breast. By the time a tumor is detected this way, said Dr. Benjamin F. Byrd Jr. of Vanderbilt University, half the patient have had the disease for nine years.
The drive for earlier detection led several years ago to nationwide trials of mammography and to a National Institutes of Health recommendation that women over 50 and younger women at high risk have a yearly mammogram. Despite evidence that mammograms indeed detect many breast cancers too small to feel, the concept of the disease is changing so fast that even the value of intensive screening for early breast cancer is being questioned.
The argument revolves around the failure of early diagnosis and treatment to affect the death rate. Over the past two decades, technical advances like the development of mammography and increasing public awareness of breast cancer unquestionably have led to earlier discovery of tumors.
Surgeons reports treating a higher percentage of patients with "stage one" breast cancer -- small tumors in the breast that have not spread to the nearly lymph nodes.And few patients are found with advanced involvement of breast and muscle tissues when they first seek treatment.
Nearly half the tumors picked up by the test are too small to be felt on physical examination. In only 15 to 20 percent of the patients found to have tumors has the cancer reached the lymph nodes, which are examined because the spread of cancer there correlates with spread to other parts of the body.
Although it is too soon to determine the impact of mammography on survival, the general trend toward earlier diagnosis has been going on long enough to detect some decrease in the number of patients dying from breast cancer.
But "the overall mortality is remarkably stable," Cole said. This suggests to him that recent progress in diagnosis and treatment may have no impact on patients with truly malignant disease.
Cole suggested that many of the tumors uncovered by mammography grow slowly and might never spread significantly or produce symptoms. Such tumors might otherwise have gone unnoticed forever.
"It's a question of overdiagnosis of minimally malignant cancer," he said.
Maurice S. Fox, a biologist at the Massachusetts Institute of Technology, analyzed breast cancer deaths in the United States between 1950 and 1973 and found they could be separated into two distinct groups.
One group, 40 percent of all breast cancer patients, died within 2 1/2 years of diagnosis. The remaining 60 percent had a low cancer death rate with half of the patients in the group still alive 30 years after diagnosis.
The implication of Fox's findings, which were published this year, is that there are two general categories of breast cancer: A fast-growing, rapidly fatal disease unaffected by recent advances, and a less malignant-- or even nonmalignant -- disease that kills its victim slowly or not at all.
The trouble is, Fox concluded, no one knows how to tell the difference.
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