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Chapter One WHAT MAKES BREAST CANCER GROW THE MYTH OF THE EUREKA FACTOR Many of us in medicine have been brought up to believe in the "lone gunman" theory of breast cancer, which suggests that a single event or toxin or food "causes" cancer. You will read hundreds of news accounts over the years of foods linked to an increased risk of breast cancer. There have been lots of suspects, ranging from a high-fat diet and red meat to pesticides in foods, but they all have disappointed researchers. Why? What these researchers really want to find is a food that increases the risk by 500 percent. That would constitute a Eureka factor ... a factor that almost certainly causes breast cancer. But unfortunately, none of these ever eked out a risk much more than 20 or 30 percent -- very unimpressive numbers. That has caused many scientists and doctors to give up on finding or pursuing a breast cancer diet.     How then can food's role in cancer development be explained? The answer is that many factors have to be added together to develop and grow a breast tumor. These factors are not simply thrown together into a toxic soup. They fall neatly into place as part of a pathway that causes cancer cells to divide and grow. There is not one food that causes cancer but a well-defined series of foods that participate. Like a series of dominoes that need to fall, one onto another, a chain of events needs to occur before a cancer can grow. This chain reaction is set off by surprisingly few foods and can require only a few steps to blunt or block it. That's because these factors can create an astounding synergistic effect. Where one nutritional factor may have little influence, several together may exert a very damaging effect or a very powerful protective effect. "A favorable change in risk cannot be attributed to a single factor. A change in a woman's entire dietary pattern is probably responsible for reducing risk. That is, a diet high in fiber, fruits and vegetables and exercise, and low in fat and alcohol consumption," explains Steven Clinton, M.D., of Harvard's Dana Farber Cancer Center.     As an example, in rural South Africa, women have a breast cancer risk of four per 100,000, about 90 percent less than American women. They have a moderately low-fat diet, lots of fiber, and a modest number of calories. Each of those factors alone has little influence and has failed to produce any results in American women. But all three of these protective factors linked together yield remarkable, virtually unbeatable results.     This chapter lays out the chain of events that leads to breast cancer. As you will see there are only about half a dozen steps. That's good news, because as we've seen in rural South African women, every step is a potential target for prevention with the right foods -- and the great news is that foods DO target each step.     Cancer development is divided into two stages. The first is cancer initiation, when a genetic mistake turns a cell cancerous. The second is promotion, which causes this cancerous cell to divide, grow, and spread. Since foods exert their most powerful effect on blocking cancer promotion, let's consider that first. CANCER PROMOTION: THE ESTROGEN EFFECT Breast cancer is called a "hormonally driven" tumor. That means the development and growth of the tumor is spurred by the body's hormones. In breast cancer, it is the hormone estrogen that primarily drives its development and growth. On balance, estrogen is an enormously healthful hormone.     We know estrogen primarily for its effect on the secondary sex characteristics in women, from growth of the uterus and thickening of the vaginal lining to breast development. Estrogen also has a variety of roles that promote great health. Estrogen protects the heart by making more good cholesterol and less bad cholesterol as well as keeping blood vessels pliable so they don't stiffen with age. Estrogen protects against bone loss by helping to absorb calcium from the bloodstream. In the urinary tract, estrogen helps to maintain the outer membranes of the urethra and bladder to prevent infections. Estrogen stimulates water retention and oil lubrication in the epidermis, so that skin remains soft and youthful. Scientists are just beginning to learn that estrogen interacts with nerve growth factors to protect brain cells from degenerating. Estrogen has been shown, in animal studies, to increase the number of connections between brain cells responsible for thought, movement, instinctive response, and learning. It also helps the brain to imprint new memories.     Although we talk about estrogen as if it were a single hormone, there are actually several different forms of estrogens. As you read this book, the key definitions to keep in mind are those for strong and weak estrogens, good and bad estrogens, and chemical estrogens. Estradiol is referred to as a "strong estrogen" in this book. This is the principal estrogen and is the most powerful natural estrogen produced by the body. There are also "weak estrogens" that counterbalance "strong estrogens." "Weak estrogens" are also called "plant estrogens," since these come from soybeans and flaxseed. The Strang Cancer Prevention Center in New York City has also popularized the idea of "good" and "bad" estrogens. As you'll read, estrogens become "good" or "bad" as the body prepares them for excretion from the body after their useful life is finished. One excretion pathway makes "good" estrogens, the other makes "bad" estrogens. This is explained at greater length in the chapter "Step 3: Make Good Estrogens." For now it's important to remember that there are both strong and weak estrogens and good and bad estrogens. The strong and weak are the active estrogens that circulate in the bloodstream. Good and bad estrogens are waste products. Chemical estrogens are just that, chemicals found in the environment, especially pesticides, that act like real estrogens in the body. Finally, there are "anti" estrogens. These are drugs, such as tamoxifen and raloxifene, that Completely block the effects of estrogen in the breast.     All estrogens have one feature in common, they must lock on to a receptor to work. Receptors are "switches" that turn biological systems on, as an electrical switch would turn a light on. There are several critical differences. First is that the receptor is turned on only by a molecule that precisely fits the receptor, like a key into a lock. In this case, the key is estrogen. Recall the different-shaped blocks children play with, which have different-shaped matching holes to put them into: round, square, rectangular, for example. Think of an estrogen receptor as being a triangular hole. Only triangular-shaped estrogen of precisely the same size will fit. A square or round block would have no chance. That means that estrogen can fit into the receptor but other kinds of hormones cannot.     Estrogen works its widespread wonders because the brain, bone, skin, heart, uterus, and dozens of other body parts have these estrogen receptors. So with so many wonderful qualities, how could estrogen ever be considered harmful? There is one other body part, loaded with estrogen receptors that soak up estrogen from your bloodstream. It is the breast. When too many strong, bad, or chemical estrogens reach these receptors in the breast, the potential for cancerous growth rises. ANATOMY OF THE BREAST The mature female breast is made up of millions of tiny milk-producing sacs. Milk flows from these sacs into milk ducts that carry milk to the nipple. These milk-producing sacs and the milk ducts have an inner lining. Picture for a moment the ceramic tiles that might line the walls of a tunnel or an ancient aqueduct. Like these ceramic tiles, a special cell called an epithelial cell lines the inner surfaces of the milk sacs and milk ducts through which the milk passes. This, as we'll see, is the breast's Achilles' heel. WHAT ESTROGEN DOES Estrogen directly affects these epithelial cells that make up the milk sacs and ducts in the breast by attaching to their receptors. It is in these milk duct cells that cancer develops. Estrogen causes these cells to divide more often and more rapidly, creating thousands of new cells. It does this by turning on many genes responsible for growth and proliferation. Each time these cells divide there is the chance for a mistake to be made, leading to cancerous changes in the cell. Lots of estrogen causes these cells to divide, multiply, and grow even more quickly. It does this by speeding up the cell's "cycle clock." That is, each cell has a gene clock that dictates how quickly or slowly it grows and replicates itself. Lots of estrogen speeds up this clock. If these are cancerous cells what they need to divide and flourish is fuel, and that fuel is estrogen.     Let's follow the estrogen pathway from the time estrogen is produced, along its journey through the bloodstream to the estrogen receptors and its eventual effect on DNA. Remember that foods can powerfully block every one of these processes. We'll see how in the following chapter. EXCESS ESTROGEN The ovaries, adrenals, and fat cells are the key estrogen factories. If their production goes into high gear, large amounts of estrogens are secreted into your bloodstream and that increases your risk of breast cancer. Let's look at the evidence. Researchers at New York University measured estrogen levels in women long before they ever developed breast cancer. Years later the NYU Women's Health Study found that those post-menopausal women who developed breast cancer had a markedly higher amount of estrogen measured in their blood than those women who did not have cancer. A study of Chinese women showed that the higher their estrogen levels, the higher the risk of breast cancer. Also, American women with a family history of breast cancer have higher levels of estrogen. Now look at the protective effect on women who produce very little estrogen. Women who underwent total hysterectomies before age 40 had a striking 75 percent lower incidence of breast cancer. Since the ovaries were removed, their body produced very little estrogen. These are just a few examples. In all, there are nearly a hundred good studies that associate high estrogen levels with a high risk of breast cancer ... and low levels with low risk. How much your risk of cancer rises also depends on the kind of estrogen that attaches to the estrogen receptors in the breast. Let's now look more closely at the different kinds of estrogens that can increase the risk of breast cancer. Strong Estrogens Consider that estrogen, represented as a triangular block, has to fit into a triangular receptor. Think of that block as a battery. The strongest estrogen, estradiol, may carry the power of a big car battery -- greatly increasing the risk of cancer. Why? When estradiol attaches to the estrogen receptor it creates a powerful signal inside the breast cell for cell growth. Other estrogens might carry the power of a small penlight battery. Weak estrogens might have the power of a very small camera battery. The more powerful the estrogen, the greater its cancer-promoting potential. Very weak estrogens may actually protect against cancer by blocking access to the receptor, so powerful estrogens cannot insert themselves. In essence, all of the triangular holes get filled up by the weaker estrogen, leaving no more space for the powerful estrogens. That means very little power is delivered to the cell and the signal that reaches the cell's DNA is weak, creating very little potential for cell growth. Chemical Estrogens Natural and plant estrogens aren't the only ones that can attach to breast receptors. So can certain synthetic chemicals. Pesticides in our food and water, called chemical estrogens, can mimic the biologic actions of estrogen. That's because they have the same "triangular" shape as natural estrogens made by the body. They are so similar in their molecular composition to natural estrogens that the estrogen receptor can't tell the difference between them. These chemical estrogens lock right into the estrogen receptors and stimulate cells in the milk ducts to divide and grow, just as real estrogens do. Although there are only minute quantities of these pesticides in our food and water, the breast can concentrate them to highly toxic levels. How? As we've seen, the breast is constructed from milk duct cells that are surrounded and supported by fat cells. These fat cells can concentrate chemicals to toxic levels. For instance the breast fat cell absorbs a form of the pesticide DDT from the bloodstream and stores it at concentrations 700 hundred times greater than is found in the blood. Bad Estrogens At the end of the day, estrogen is discarded by the body. To make estrogen easier to dispose of, the body changes estrogen into different forms. But which disposal form your body makes may determine whether or not you get breast cancer, according to researchers at the Strang Cancer Prevention Center in New York. The breakdown products are a "good" estrogen or a "bad" estrogen, much like the "good" and "bad" cholesterol in your blood. The good appears to protect against breast cancer, whereas the bad may play a very powerful role in triggering the development of cancer. Foods can increase the amount of "good" estrogen you make. Among Japanese women who had breast cancer, those with high counts of "good" estrogen had no spread to the lymph nodes. Among those who had low counts of "good" estrogen, there was spread to lymph nodes. Later in this book you will find an entire chapter on good and bad estrogens. Recycled Estrogens Estrogen circulates through the bloodstream for less than a day, then is disposed of by the body, which transports it from the bloodstream through the liver and into the bowel for excretion. Once estrogen is put into the bowel for disposal, you'd think that was the end. Unfortunately, estrogen can be absorbed from the bowel into the bloodstream, which can contribute to higher estrogen levels in the blood. This happens when there is too little fiber to bind estrogen and carry it from the bowel. Free Estrogen Most estrogen is transported from the ovaries and other production sites in the bloodstream on what is a called a carrier molecule. You might think of the estrogen as a triangular log tightly strapped onto a barge for transport down a river, rather than floating freely in the river by itself. Only estrogen that is "free" can attach to an estrogen receptor in the breast. The higher the amount of "free" estrogen in your blood the higher the risk of breast cancer. Estrogen cannot make its way into the breast to attach to a receptor so long as it is attached to its carrier. The technical name for the carrier is sex hormone binding globulin, or SHBG. As we'll see, binding more of the free estrogen by building more carriers is a significant way to lower your risk. Anti-estrogens These are drugs such as tamoxifen and raloxifene. They dramatically cut the estrogen effect, blocking access of all estrogens to the estrogen receptor so that there is no signal for growth inside the breast cell. PROLONGED EXPOSURE TO ESTROGENS High levels of estrogen are only one way to increase your risk. The other is to increase the total amount of time you are exposed to estrogens over the course of a lifetime. The more years you menstruate, the greater your risk of cancer. Both an early menarche and a late menopause create years of increased estrogen exposure. Girls with the earliest menarche, before age 14, have a 30 percent increased risk of cancer. Women who have a later menopause, say age 55, have a 50 percent higher risk of breast cancer than those whose menopause occurs before age 45. The most fascinating evidence comes from Catholic nuns studied in Europe over 300 years ago. These nuns had a markedly higher level of breast cancer than married women with children. They obviously weren't being studied at the time for estrogen levels, or in any systematic, scientific way. But in hindsight we recognize the cause of their cancer was the uninterrupted estrogen flow. BOOSTING THE EFFECT OF ESTROGEN After estrogen has completed its journey from the ovaries through the bloodstream to the receptor, the game is far from over. The only way estrogen works is by attaching to a receptor. Once estrogen attaches to the receptor, the signal can be magnified enormously to create a strikingly higher risk of breast cancer. This is called a "booster" effect. That means, whatever power estrogen carries to the receptor, that power can be magnified so that the final effect on cell growth is tremendous. As we'll see, the kinds of fats you eat determine the amount of booster effect. CANCER INITIATION: PULLING THE TRIGGER So far we've seen the role of estrogen as a fuel that causes cells to divide and grow. But something must still "pull the trigger" to initiate changes in the cell that turn it cancerous. When scientists say they are looking for the "cause" of breast cancer they are really looking for whatever substance or toxin damages the cell's DNA. DNA is thought of as an extraordinary blueprint that carries all of the instructions for the complete building, care, and maintenance of every part of the human body. But DNA goes beyond mere blueprints; it is also chief architect and general contractor, manufacturing the elements that build every element of every cell in the body.     The entire complement of DNA contains the equivalent of 500,000 typewritten pages. Imagine having those half million pages on a computer disk and having the disk constantly zapped by chaotic electrical surges, 24 hours a day, 7 days a week, year in and year out for 80 years -- without ever suffering a single misspelling or loss of data -- while being used by tens of thousands of computer operators. Error-free operation is just not possible and that's the trouble with DNA. It's under a blistering daylong attack. These blueprints get zapped up to 1,000 times every day by the toxins that are in our environment and in the foods that we eat. To protect itself, DNA has an enormous repair crew to repair the damage. This repair crew has to spot that one error out of a billion and fix it. Should, however, the repair crew get taken out of action by potent carcinogens -- or should the damage be so devastating that it can't be repaired -- the damaged DNA reprograms a normal cell and turns it into a cancer cell.     Doctors have classically been led to believe that there is just a single "zap" that pulls the trigger and creates an error that leads to cancer. With breast cancer, nothing could be further from the truth. The new emerging concept is that there are lots of mutations and genetic defects. For the most benign of cancers, there are at least half a dozen errors. For the most severe and aggressive, there are up to 50 errors. Each one may come from a different cancer-causing substance. When scientists look at DNA, they see a distinct pattern of damage that is characteristic of environmental damage. The gene most frequently damaged is called P53. But the distinct patterns of damage vary widely from one population of women to another. So it's likely that women in Austria suffer a very different kind of damage than women in Los Angeles or Australia. Thus it is very difficult to come up with one approach to preventing cancer initiation. But there is one new emerging concept -- an overall measure of the daily siege that DNA undergoes. It goes by the name "oxidative load."     "Oxidative load" sounds fairly innocuous, but here's what it means. Elements in the body called free radicals are responsible for the cellular damage that occurs with aging, in heart disease, cancer, and most degenerative diseases ... regardless of what the original toxin may have been. These free radicals cut and hack away at DNA at a furious pace. The more free radicals clustered around doing their damage to your DNA, the higher the "oxidative load." Inside your body they are created from fat metabolism. External sources range from solar and ionizing radiation to cigarette smoke, air pollutants, heavy metals, ozone, organic solvents, pesticides, and food additives. More to the point, researchers can actually see a higher oxidative stress in the breasts of women with breast cancer than in those who are cancer-free.     So, in summary, while we can't single out specific foods or toxins that initiate breast cancer, we can measure oxidative load. The lower that load, the lower your risk of cancer, and certain foods dramatically reduce oxidative load. The following chapter looks first at how to cut the estrogen effect and then at how to lower oxidative load. Copyright © 1998 Robert Arnot, M.D.. All rights reserved.