The Reader 6/9/05
THE BIOLOGY AND POLITICS OF BREAST CANCER
by Ken Fischman, Ph.D.
Dedicated to the memories of:
A Parable for Our Time
People in a town along a river spotted a person drowning in the turbulent waters and attempted to rescue him. The next day they noticed more and more people struggling in the torrent, and redoubled their efforts to save them. They became experts in river rescue and invented more and more ways to try to retrieve and resuscitate the drowning victims. In fact, as time went on, they became world-famous for their ever-more innovative river rescue techniques, of which they were quite proud.
However, don’t you think it odd that in all this time, they never thought to look upstream to find out who was pushing these people in? (adapted from Living Downstream, by Sandra Steingraber,)
In this article, I invite the reader to walk with me upstream, along the banks of that river.
The Biology of Cancer
In order for the reader to better understand what cancer is and what its medical and political implications are, it is necessary first to cover a few basic biological concepts.
Cancer cells are cells that no longer obey the body’s controls. They revert to a primitive state, and have a tendency for perpetual growth and tumor formation. Genes are the basic units of heredity within cells. You can think of them as a set of blueprints for building and controlling your body. There are thousands of different kinds of genes in human beings.
DNA is the chemical stuff that the genes are made of. DNA is an extremely long molecule, made of thousands of subunits. The genes are attached to each other in groups of hundreds, like a string of pearls. There are 46 of these strings in each human cell and we call them Chromosomes.
A remarkable property of genes is their ability to make identical copies of themselves. They distribute these copies, one to each of the new cells produced through a process called Cell Division. Therefore, every cell in your body contains a duplicate set of genes.
If every cell in your body has an identical set of genes, then why do some cells look and act differently from each other? Muscle cells produce a protein, called myosin, that enables them to contract. Brain cells produce neurotransmitters, which enable them to send signals to other cells. The explanation is that all of the genes in a cell are not functioning all of the time. There is one set of genes functioning in a brain cell and a somewhat different set in a muscle cell.
Which groups are functioning is controlled in two different ways. The first way is controlled by other genes; the second, is by chemical signals from outside the genes, which may even come from distant parts of the body. Hormones are the chemical messengers involved in this kind of remote control.
An Oncogene (“cancer gene”) is one type of controller gene that plays important roles in Breast Cancer (BRCA). It is normally involved in directing growth and cell division. It is only when genes of this type are malfunctioning that they cause cancer. You can think of a faulty Oncogene as if it were a stuck accelerator on an automobile.
There are two types of cancer: (1) inherited and (2) acquired:
The inherited type occurs as a defect in the person’s genes and has been passed on to him/her through the egg or sperm from one, or both parents . The defective gene is therefore found in every cell of his body. This gene can be passed on to the next generation, again through the reproductive cells. Familial BRCA is of this type.
Acquired cancer, on the other hand, occurs due to changes that take place in the genes in at least one of the person’s cells during his lifetime. If it does not occur in one of his reproductive cells, it cannot be passed on to the next generation. Examples are: lung cancer, Leukemias, and most BRCAs.
A mutation is a change in a gene. The change is passed on to the cells resulting from division of the cell that carries the mutated gene. When these cells divide in their turn, the mutation is passed on again, and so on and so on, until there can be millions of such cells, each with the identical defect.
There are several ways in which these mutations can come about. One way is for a mistake to happen while the DNA is duplicating itself. Another way is for an environmental agent, like radiation or a chemical, to come in later, and damage the DNA in some way. A third way is for a mistake to occur later, during cell division. The chromosomes might break or not be distributed equally between the resulting cells. Any one of these kinds of mutations, and sometimes all three, can be involved in producing a cancer cell.
Breast Cancer – A World-Wide Epidemic
Breast Cancer is a disease that strikes one woman in seven. The incidence of BRCA has risen steadily since World War II. It increased 60% between 1950 and 1988. This increase has nothing to do with increased longevity. For example, women born in the USA between 1947 – 1958 have three times the rate of breast cancer as their grandmothers had at same age. In 1991, 170,000 American women were diagnosed with BRCA. The latest available figures are for 2002, with 205,000 new cases. That is an 20 % increase in eleven years.
This type of cancer is effecting younger women more and more. BRCA kills more women between the ages of 35-50 than any other disease. Why has this veritable explosion in BRCA occurred?
The American Cancer Society (ACS) points to ‘lifestyle’ and heredity as the prime villains. Their brochures exhort women to: (1) exercise, (2) lower fat in their diets, (3) perform breast self-examinations, (4) examine their family history, and (5) receive regular mammograms in order to detect BRCA, etc. Yet, the great majority of BRCAs cannot be explained by either inheritance or so-called ‘lifestyle’ factors. Let’s examine a few circumstances:
The list of chemicals and other environmental agents, known or suspected to be cancer-causing is a very long one. Yet, in all this time, only about a dozen have been banned by U.S. government agencies. Here are just a few of the more egregious cases.
Twenty seven years ago evidence was presented that women working in the plastics industry and exposed to Vinyl Chloride (VC), faced an increased risk of BRCA. (J. Occup. Med., 1977). VC was acknowledged by the Environmental Protection Agency (EPA) to be a human carcinogen (cancer-causing agent). It was not banned however, and enormous quantities of it are still being produced and distributed around the world.
Polychlorinated Biphenyls, better known as PCBs, are strongly suspected of causing BRCA. General Electric dumped PCBs into the Hudson River in New York state until the 1970s. There are an estimated one million pounds lying on the bottom of a 40 mile stretch of the river .
Well known risk factors for BRCA are: (1) early 1st menstruation, (2) late menopause, and (3) late or no childbirths. What these factors have in common is that they all increase a woman’s lifetime exposure to estrogens.
Estrogens are hormones, secreted by a woman’s ovaries each month. It effects only cells with Estrogen Receptors on their surface. The hormone attaches to the receptor. Then the Estrogen-Receptor complex penetrates into the nucleus and activates one particular set of genes while turning off another set. The net effect is to increase cell proliferation in: (a) the vagina, (b) the uterus, and (c) the breast. Estrogen therefore stimulates ovulation, menstruation, and breast development.
A full term pregnancy early in a woman’s life protects against BRCA. Why? The current theory is that breasts do not completely develop until the last few months of the first pregnancy. Once they are developed, cell division in them slows, and because DNA in non-dividing cells is less sensitive to damage from radiation and chemicals, these women are less vulnerable to BRCA.
Early onset of puberty is also a strong risk factor for BRCA. Consider the following facts: The average age of female puberty in the 1940s was 13 – 14 years. At present it is 10 – 11 among whites, and even earlier among black girls. Some possible explanations are:
Since WWII, over 70,000 Synthetic Organic Chemicals (SOCs) have been produced, some in enormous quantities, and distributed all over the world. They have infiltrated our air, water, food, and our very bodies.
(1) many pesticides, herbicides and other SOCs are endocrine-imitators, (i.e they have estrogenic effects). SOCs may hasten the onset of puberty. There is strong evidence that Atrazine, the most widely used herbicide in the world, has this type of effect. Despite this, the EPA has recently refused to ban it.
(2) Americans eat a greater proportion of meat in their diets than any other people. Chickens and cattle are often treated with hormones in order to make them grow faster.
Women who have fatty diets have greater risk for BRCA. The NCI, and many other authorities, have concluded from this that fat causes cancer, and they have told women to change their lifestyles by doing more exercise and eating less fatty foods. Some scientists however believe that it is not the fat, but what is in the fat that causes BRCA. Many SOCs are fat-soluble, and therefore tend to concentrate in fatty tissue such as the breast and bone marrow. The more obese you are, the more carcinogens you accumulate. (Carcinogen concentration in fatty tissues may also explain why the incidence of Multiple Myeloma, a hitherto rare cancer of the bone marrow, has increased ten-fold in the past few decades) .
SOCs not only lodge in fatty tissues, they become biomagnified (concentrated) there.) In addition, SOCs are not easily metabolized and excreted. Therefore, they may linger in tissues for years. Some researchers have called fat the body’s hazardous waste site.
Inherited Breast cancers
You have probably heard of Breast Cancer Families, in which several generations of women develop BRCA. Two BRCA genes have been identified: BRCA-1 & BRCA-2. Women who possess BRCA-1 also have a higher risk for Ovarian cancer, but this does not appear to be so for those who have BRCA-2. Women who inherit either mutant gene are at much greater risk earlier in their lives for subsequent steps in the carcinogenesis process (described further on in this article). This is demonstrated by the high percentage of women possessing the gene, who get BRCA in their 20s (40%), compared with the much lower percentage of women who have the gene, who get BRCA in their 80s(1%).
A good way to distinguish between inherited and environmentally-induced diseases is to compare populations in different parts of the world. It has been observed for example, that BRCA rates in the U.S. are thirty times higher than in parts of Africa. We can also evaluate groups of people before and after they migrate from an area of high disease incidence to one of low incidence, or vice versa. BRCA rates rise in Jewish women who migrate from North Africa to Israel; rates decrease when English women migrate to Australia. Their genes of course remain the same. Only their environment has changed.
As previously mentioned, inherited Breast Cancers were the predominant form of BRCA before the 1940s. Their incidence has not increased in the ensuing years. They are now a tiny minority of all BRCA cases, probably no more than 5 – 10%, and effecting only about 1/3 of 1% of all women. The other 90 – 95% of BRCAs are classified by US government agencies as ‘sporadic’, meaning that the cause is unknown.
Saying that most BRCAs are ‘sporadic’ reminds me of a story about a novice boxer. His manager sends him into the ring against a much more experienced opponent. He is getting badly beaten. At the end of one round he comes back to his corner with his nose bleeding, one eye almost closed, and bruises all over. His manager tries to buck him up. “You’re doing great kid” he says “You have him on the run. He hasn’t laid a glove on you.” The kid turns around and looks at the manager. “Yeh?”, he says, “Well you better keep an eye on the referee because someone out there is sure beatin the crap out of me!”
Mechanism of Carcinogenesis
Normal cells do not become cancer cells in one swoop. For example, Benzo(a)pyrene is the principal cancer-causing agent in tobacco smoke. It and Croton oil are much more effective in inducing cancer when applied sequentially, rather than together. This is evidence that there is more than one step in cancer production.
Mutations are usually chance events that could occur in any one of the cell’s thousands of genes. Routine errors could be made during DNA replication, or a gene could be damaged by a carcinogenic agent. The first step toward cancer is a mutation. This is obvious because tumors continue to grow even after the carcinogen is removed. Therefore, an event has occurred that is being passed from generation to generation of its cells.
Another clue that cancer is a multi-step process is the long lag time, or latent period after first exposure to a carcinogen before a recognizable cancer develops. It may take many years. This lag time occurs because two or more rare chance events have to take place in order for a cell to become cancerous. The probability that two rare events will both happen is the product of the chance for each of them to happen by itself.
A simple illustration of this is flipping a penny. If you flip it once, the chance that it will come up heads is 1/2. If you flip it twice, the chance that it will come up heads both times is 1/2 X 1/2, or 1/4. Imagine then that if the chances that each of these two mutations occurring in the same cell is a couple of thousand to one, the probability of both happening is a very long shot indeed. Time however, is an additional factor. The longer the cell lives, the more likely it is that the second mutation will eventually occur.
The stages for inducing a cancer cell are called: (1) Initiation, (2) Promotion, and (3) Progression
1. Initiation is usually a small subtle lesion in DNA. There are no visible changes, but it can be recognized by the body and reacted to. The immune system may recognize changes in the cell surface and then destroy the aberrant cell. Any weakening in these defense mechanisms could lead to retention of initiated and therefore potentially cancerous cells, making it more likely that some of them will survive to reach the next stage of carcinogenesis.
2. Promotion unfolds over long time period and does not involve mutations, but encourages changes in which certain genes are activated. Promotion can be stimulated by substances like Estrogens. Here is the good news. When the influence of these substances is removed, cells usually revert back to the previous stage.
3. Progression – Mutations pile up at the molecular (i.e. DNA) level and chromosomes become increasingly damaged and unstable. Some of these changed cells become cancer cells. The production of many different chromosome abnormalities in the same tumor has the effect of making it a heterogeneous group of cells with different properties. It makes diagnosis & treatment more difficult.
Many carcinogens have multiple roles. They can take part in more than one of these steps, and do so at: (1) different times, and (2) different concentrations. Dioxins, which are common byproducts of incineration, suppress immunity, as well as induce mutations. This is why there is no such thing as a “safe” dose of a carcinogen. Similar exposures may pose very different threats to different people or at different times. e.g., those whose cells are already initiated, may react to trace amounts and move to the next stages.
We are constantly exposed to more than one type of carcinogen at the same time and to many exposures of the same carcinogens over periods of time. There may be cumulative effects from multiple exposures. DDT and another carcinogen, called AAPA, accelerate tumor formation when applied simultaneously, although neither alone is capable of doing so. This effect is called synergism.
A Real War on Cancer
For many years, BRCA research went under-funded and the whole issue of BRCA was virtually ignored by both government and private research institutions.
Finally, in the early nineties, women began to take note of the success of the Gay Community in turning these institutions’ attention to AIDs research. Women quickly showed that they had learned a lesson in the politics of disease. The Breast Cancer Fund, founded by women, emphasizes that women must stop thinking of BRCA as only a personal tragedy, and demand more emphasis on true prevention, removal of carcinogens from our environment.
October is Breast Cancer Awareness Month. Women are showered at that time with literature emphasizing prevention and early detection. The message is: get a mammogram, go on a low fat diet, exercise, and cut back on alcohol consumption.
There is not one word about primary prevention though – removing chemical carcinogens from our environment. Is this merely an oversight?
The chief sponsor of Breast Cancer Awareness Month is AstraZenica, a giant multinational corporation, which manufactures the BRCA chemo- prevention drug, Tamoxifen. It also produces herbicides and fungicides. In addition, AstraZenica now owns the Salick chain of cancer treatment centers.
This seems like a cozy arrangement for AstraZenica. It produces suspected BRCA carcinogens. It is also involved in the treatment of cancer, and it is now selling a BRCA-prevention drug. It also gets all kinds of good publicity from Breast Cancer Prevention Month, and uses that to deflect our attention away from the environmental causes of cancer.
Sandra Steingraber, author of “Living Downstream”, a book documenting the environmental causes of cancer, states that “By emphasizing personal habits rather than carcinogens, they frame the cause of the disease as a problem of behavior rather than as a problem of exposure to disease-causing agents…. It presumes that the ongoing contamination of our air, food, & water is an immutable fact of the human condition to which we must accommodate ourselves.”
How Can We Really Win The “War On Cancer”?
The most important action we can take is to make the ‘Precautionary Principle’ the law of the land. The Principle states, in part, that "When an activity raises threats of harm to human health, or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. In this context,
the proponent of an activity, rather than the public, should bear the burden of
proof." The European Union has already invoked the Precautionary Principle, first against Genetically Engineered food, and now against suspected carcinogenic agents.
Last, but not least, join an activist organization that will represent your interests. The next time that you are asked to donate to a ‘cure for cancer’, you might consider the Breast Cancer Fund when you ponder where your money will be most effective.