Breast cancer.

You can't escape breast cancer. Most women won't get the disease, but almost all women worry about it.

It's there every time they do (or delay) a self-exam or mammogram. It's there every time they think of the friends, relatives, or acquaintances whose bodies and lives have been altered by surgery, chemotherapy, or other treatment. It's there every time they remember the women, young and old, who have already died.

And, as far as anyone can tell, it's not going away any time soon.

"Breast cancer is definitely a tough problem to crack," says Walter Willett, who heads the nutrition department at the Harvard School of Public Health. "We've done a lot of research, but most of what we've learned doesn't translate into public health advice for women."

For more than a decade, researchers have tried to prove that a high-fat diet was a major culprit. Now they're also taking a closer look at alcohol, pesticides, excess weight, and body shape, as well as possible protectors like exercise, soy foods, and a plant-based diet.

"We're a few decades late in getting started," says Willett. "But we'll know a lot more in the next five years."

One out of eight American women will get breast cancer in her lifetime [see "The Risk of Getting Breast Cancer"). It doesn't have to be that way.

How do we know?

"Breast cancer rates are four to seven times higher in the U.S. than in Asia," says Regina Ziegler, a nutritional epidemiologist at the National Cancer Institute (NCI). "The difference is not explained by genetics, because when Asian women move to the U.S. their risk doubles over a decade, and they acquire U.S. rates after several generations."[1]

What could change these women's risk so rapidly.? No one is sure.

"We have consistent evidence that an affluent, Western diet is associated math higher risk," explains Ziegler. But is it the extra calories, meat, fats, or other foods they start eating...or the fruits, vegetables, grains, soy, or other foods they stop eating that matters?

Weight and physical activity - which also change dramatically when Asian women come to the U.S. - may explain some of the jump in breast cancer rates. If they do make a difference, researchers think it may be by altering hormones.

"We know breast cancer is influenced by natural hormones," says Paolo Toniolo, an epidemiologist at New York University Medical Center. But it's not yet clear which ones matter and how to change them.

"It's hard to measure hormones accurately because they're so variable during the menstrual cycle, and they may even change in postmenopausal women as they age," explains Ziegler.

"And there are so many hormones," she adds. "Estrogens and progesterone used to receive all the attention, but now scientists are thinking about androgens, insulin, and growth factors."

The question is: Can diet, exercise, and weight alter our hormones enough to make a dent in our risk of breast cancer?

A HIGH-FAT DIET

Does a fatty diet cause breast cancer?

Look around the world, argue scientists like the American Health Foundation's Leonard Cohen. Countries with high-fat diets have more breast cancer. And animals fed high-fat diets get more tumors.[2]

But others, led by Harvard's Walter Willett, disagree. "Thirty years ago, women in the Mediterranean had only a third of our breast cancer rates despite a high-fat diet that got 40 percent of its calories from fat," he points out. Since then, he adds, "rates in the Mediterranean have been rising rapidly."

His much-publicized analysis of the Nurses' Health Study showed no difference in breast cancer risk between women who got 44 percent of their calories from fat and women who got 23 percent.[3] Most Similar studies have also failed to find a strong link.

"Overall, I think it's unlikely that there is a real association between total fat and breast cancer," says Geoffrey Howe, a cancer expert at Columbia University who had long argued that fat was a culprit.

"I've changed my mind," he says. "As the studies got better, the evidence got weaker and weaker."

But to others, fat is still suspect.

First, says Cohen, the diets of Americans are all so fatty that you wouldn't expect to see protection in the nurses who ate less fat.

"If you have to get down below 15 percent of calories from fat to see an effect, it's true that we wouldn't have seen one," responds Willett. "But," he adds, "we did look at a substantial range of fat intake."

Second, it's possible that studies like Willett's don't measure how much fat people eat with enough precision. "The food frequency questionnaires we use to measure fat are very crude measures of what people eat," says the NCI's Laurence Freedman. "So we're left not being at all sure what those studies mean."

A third explanation for the weak link between fat and breast cancer is that a woman's current diet may matter less than her childhood diet. "Diet may have its greatest effect during puberty or adolescence, when breasts are still forming," says Leslie Bernstein, a breast cancer expert at the University of Southern California.

In an effort to break the impasse, the government is mounting the Women's Health Initiative, a $628 million trial involving 164,000 women. It will test - among other things - whether a low-fat diet that's high in fruits, vegetables, and grains leads to fewer cases of breast cancer than a typical U.S. diet. Results are due in the year 201 0.

OLIVE OIL

What does Leonard Cohen advise his wife to eat?

"I tell her to keep fat to 20 percent of calories, to eat more beans, and to cook in olive oil."

That's because in some animal studies, olive oil doesn't promote tumors, as corn and other polyunsaturated vegetable oils do.[2]

And people in Mediterranean countries that have a low risk of breast cancer eat diets that are low in saturated fat and rich in olive oil which is monounsaturated.

"Southern Italy and Greece have a lower risk of breast cancer than other parts of Europe," says NYU's Toniolo. And a few studies have found that breast cancer patients in Spain and Greece consumed less olive oil than their healthy counterparts.[4]

That doesn't mean that women should pour olive oil over everything they eat. First, says Toniolo, "while the evidence is very promising, it's still too early."

Second, the idea isn't to add olive oil, especially if you're trying to cut calories. Instead, olive oil should replace other fats - and not just the fat in butter, margarine, other vegetable oils, and fried foods, but the fats in meat, poultry, and dairy products.

Eating less meat and dairy means eating more fruits, vegetables, grains, and beans - other things that may lower your risk.

PLANT FOODS

"The secret of prevention is in the diets of women from countries math low rates of breast cancer," says Toniolo.

That's what led researchers to think that a low-fat diet was key. Now, he says, it's leading them to other foods in the traditional diets that those women are abandoning."

When Asian women move to the U.S., "the first thing they throw out is the soy, and they start to eat meat instead," said Herman Adlercreutz of the University of Helsinki at a 1994 symposium on cancer.

Isoflavonoids, found largely in soy foods - like tofu, miso, and soy milk, but not soy sauce or soy formulas like Ensure - are known as "phytoestrogens," or plant estrogens. "Phytoestrogens can serve as weak estrogens, which means they'll interfere with ordinary estrogen," says the NCI's Ziegler. (If estrogen promotes breast tumors, anything that interferes with it should cut a woman's risk.)

But the case is far from closed. One inconsistency: In two recent studies, Japanese women with breast cancer consumed no less soy than their healthy counterparts.[5] And, notes Willett, "virtually all poorer countries have low rates of breast cancer, but Japan and China are almost the only countries that eat soy."

What those other poor countries eat is a plant-based diet - that is, mostly grains, fruits, vegetables, and beans. Something in those plant foods may protect the breast. But what?

Could it be the lignans in beans and whole grains, which may act as weak estrogens? "American Indians and Hispanics eat more beans and have much lower rates of breast and prostate cancer," notes Cohen.

Or, could fiber protect women by making them excrete more estrogen? At least in some studies, women who ate a low-fat, high-fiber vegetarian diet excreted more estrogens.[6] But whether that changes the critical hormones in the breast is anyone's guess.

Carotenoids and other phyto-chemicals in fruits and vegetables are another possibility. But the evidence that vegetables and fruits protect the breast "isn't as consistent as it is for their protecting against cancers of the lung, mouth, throat, stomach, and colon," says Ziegler.

Nevertheless, experts recommend eating more fruits, vegetables, beans, and grains. If nothing else, they may help women stay slim.

WEIGHT & SHAPE

Until recently, most scientists ignored the link between weight and breast cancer. Being overweight raised a postmenopausal woman's risk only slightly, "so people thought it wasn't a significant risk factor," says the NCI's Rachel Ballard-Barbash.

But that's changing. "It wasn't until the early 1990s that we started to look at waist-to-hip ratio," she explains. Postmenopausal women with a higher ratio - that is, who tend to accumulate fat around their waist ("apples") rather than around their hips and thighs ("pears") - were more likely to get breast cancer in those studies.[7]

Why would body shape matter? "People who have higher waist-to-hip ratios have higher insulin levels," says Ballard-Barbash. "In laboratory studies, insulin promotes the growth of breast cancer cells."

Researchers are also starting to look at when a woman gains weight.[7] "We need to explore whether weight-gain during times of hormonal change - like pregnancy and menopause - might especially influence risk," she says.

But Ballard-Barbash - like others - is cautious. "The data are consistent, but limited," she notes.

And, like cutting fat in foods, "it may be that we'd have to get much slimmer" to reach the low risk of Asians, says Ziegler.

ALCOHOL

Avoiding too much alcohol, says Willett, "is one of the few things women can do to reduce their breast cancer risk."

He's convinced that there's an increased risk at as little as one drink a day. Below that, he's not so sure.

"At two or three drinks a week," he says, "the effect - if any - is low. So if you drink, enjoy a glass of good wine now and then."

And "if you're over 50 and have risk factors for heart disease," he adds, "alcohol will have a beneficial effect, though there are other ways to reduce the risk of heart disease."

Other researchers note that alcohol raises the risk of breast cancer only modestly. "On average, studies find a 10 percent increase in risk for women who have one drink a day compared to nondrinkers, a 20 percent increase at two drinks a day, and so on," says Matthew Longnecker, an epidemiologist at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.[8]

But those studies looked at recent drinking. In one of the few large studies that asked women about their lifetime drinking, Longnecker found almost a 40 percent increase in women who averaged one drink a day and a 70 percent increase with two daily drinks.[9]

Those numbers may seem large, but they're not. "I estimate that only four percent of all breast cancers could be attributed to alcohol," says Longnecker. It's also possible that something about drinkers other than alcohol raises their risk, he adds.

The case against alcohol got a boost in 1993, when the NCI's Marsha Reichman reported that feeding 34 premenopausal women about two drinks a day raised estrogens in their blood.[10]

That may not prove that alcohol causes breast cancer, but the link is stronger than other links with diet. "By far, the best diet evidence is for alcohol," says Willett.

EXERCISE

"Our data suggest that women who are physically active for one to three hours a week could reduce their risk of breast cancer by about 30 percent relative to inactive women," reported USC's Leslie Bernstein in 1994. Exercising at least four hours a week could cut the risk by more than half.[11]

But Bernstein was looking only at premenopausal women. She's just now studying postmenopausal women, who are far more likely to get breast cancer. And one study isn't proof.

"The evidence that exercise will prevent breast cancer is still meager and inconsistent," says Willett.

Nevertheless, notes Bernstein, there's reason to think that exercise is protective because it influences hormones and menstrual patterns.

"Women who exercise a lot may menstruate less frequently than the usual 28 days," she says. That's good, because the less often you menstruate, the less your breast cells proliferate. And the less they proliferate, researchers believe, the lower your risk.

But, she adds, "more data are needed before one can s how much of which exercise at what age will protect the breast."

PESTICIDES

As news stories go, it was a bombshell.

In April 1993, researchers released a study showing that the risk of breast cancer was four times greater in women with higher levels of pesticides like DDE in their blood than in women with lower levels.[12]

But even NYU's Toniolo, one of the study's authors, isn't convinced that organochlorine pesticides like DDE matter. "The risk of breast cancer is low in places like Southeast Asia," he points out, "where direct exposure to pesticides is high, especially among unprotected farmers. I don't think pesticides explain more than a little piece of the puzzle."

By April 1994 a second, larger study looked at women math higher levels of pesticides in their blood.[13] It suggested a possible link between pesticides and breast cancer risk among whites and African-Americans, but not Asian-Americans.

Still, most researchers want to see more data. "A high pesticide level could be a marker for meat, dairy products, and a high-fat diet," says the NCI's Sheila Zahm. In other words, it could be those foods - not the pesticides they accumulate - that increase the risk of breast cancer.

Further studies are now under way. In the meantime, says Harvard's Nancy Krieger, lead author of the 1994 study, "anyone who categorically says that organochlorine pesticides are of no concern - or have been definitively shown to cause breast cancer - is overstating the case."

OTHER LEADS, OTHER DISEASES

Those aren't all the leads researchers are tracking down. For example, breastfeeding may cut the risk of premenopausal breast cancer, especially in women who breastfeed for at least four to 12 months.[14]

Meanwhile, it's comforting to know that a plant-based diet, exercise, and staying lean may cut the odds of getting heart disease, colon cancer, and other big killers, not just breast cancer. "All the research shows that this is a healthy lifestyle," says Toniolo.

Unfortunately, it's the diet and lifestyle that most of the world is abandoning...with grave consequences.

Says Toniolo: "Now, under our very eyes, Japan, Singapore, Thailand, and Hong Kong are all seeing enormous increases in breast cancer."

RISK FACTORS FOR BREAST CANCER

What causes breast cancer? In most cases, experts don't know. Some estimate that known risk factors may account for only about half of all cases.

This table shows who falls into groups with higher risks...and how high those risks are relative to groups with the lowest risks. Comparing these "relative risks" can be tricky. For example, while a 90-percent increase in risk may sound high, it's less than two times the risk (that would be a 100-percent increase).

[TABULAR DATA OMITTED]

THE RISK OF GETTING BREAST CANCER
By age 25   one in 19,608
By age 30   one in 2,525
By age 35   one in 622
By age 40   one in 217
By age 45   one in 93
By age 50   one in 50
By age 55   one in 33
By age 60   one in 24
By age 65   one in 17
By age 70   one in 14
By age 75   one in 11
By age 80   one in 10
By age 85   one in 9
Ever        one in 8
Source: National Cancer Institute

WHAT TO DO

* Eat a plant-based diet that's rich in fruits, vegetables, whole grains, and beans.

* Cut back on the saturated and trans fats that increase your risk of heart disease. When you use oil, stick with olive.

* If you drink, keep it to no more than three alcoholic beverages a week (and not all at once).

* Exercise for at least two - and preferably four - hours a week.

* Follow the American Cancer Society's advice to get a mammogram every year after age 50 and every year or two between the ages of 40 and 49. Do a breast self-exam once a month.

* If you waist (at the smallest point between your ribs and your belly button) divided by your hips (at the largest point around your fanny) is above 0.8, cut calories and exercise more.

* Breastfood each child for several months, if possible.

* If you're a healthy postmenopausal woman and want to participate in the Women's Health Initiative, call (800) 54-WOMEN.

* If you want to get more involved in the science and politics of breast cancer, call the Breast Cancer Coalition at [phone].

[1] J. Nat'l Cancer Inst. 85: 1819, 1993. [2] J Nat'l Cancer Inst. 77: 33, 1986. [3] Journal of the American Medical Association 268: 2037, 1992. [4] Int'l. Journal of Cancer 58:774, 1994. [5] British Journal of Cancer 71:1353, 1995. [6] New England Journal of Medicine 307:1542, 1982. [7] Cancer 74 (Suppl):1090, 1994. [8] Cancer Causes and Control 5:73, 1994. [9] J Nat'l Cancer Inst. 87:923, 1995. [10] J Nat'l Cancer Inst. 85:722, 692, 1993. [11] Nat'l Cancer Inst. 86:1403, 1994. [12] J. Nat'l Cancer Inst. 85:648, 1993. [13] J Nat'l Cancer Inst. 86:589, 1994. [14] New England Journal of Medicine 330:81,1994.