Kontakt Weltweit Contact Worlwide Deutschland FUNKE Wärmeaustauscher Apparatebau GmbH Germany T: +49 51 82 / 582-0, F: +49 51 82 / 582-48 e-Mail: email@example.com, Internet: www.funke.de Australien Australia 1/105-107 Stanley Road, (Cnr Devon & Cornwall Rd), Ingleburn, Funke Gruppe Benelux Funke group firstname.lastname@example.org, www.funke-benelux.nl Brasilien
2-01.pdfSTATE OF THE EVIDENCE
What is the Connection Between Chemicals and
Breast cancer now strikes more women than any other type of cancer, the result of adramatic increase that has taken place in the industrialized world during the past halfcentury. Whereas one in 22 women were diagnosed with breast cancer in the 1940s, nowthe incidence is one in eight. Of all women who die of disease between ages 35 and 54,breast cancer is the cause in approximately one case out of four.
More American women have died of breast cancer in the last 20 years than the number ofAmericans killed in World Wars I and II, the Korean and Vietnam wars combined.
There are only two known causes of the disease -- exposure to ionizing radiation andinherited genetic defects. Although the problem of genetic defects has received muchrecent attention, it accounts for a minority of the epidemic. In the largest study everconducted among twins, published in the New England Journal of Medicine in July 2000,researchers found that twins with identical genes developed breast cancer about 27percent of the time. The rest of the time the disease occurs in women born with normalgenes and apparently is related to conditions and exposures encountered in daily life. Inshort, breast cancer is more often made than born.
Cancer certainly runs in families, but not just because children and siblings sharedefective genes. A study in 1988 found that adopted children whose adoptive parents diedof cancer had five times the chance of getting the same disease, revealing a connection tocommon experiences and lifestyles independent of inherited genes.
Poor eating and drinking habits are associated with a higher risk of breast cancer, as areuncontrollable factors such as early puberty or late menopause and social forces such ashigher income and age at first full-term pregnancy. However, even when all known riskfactors are added together more than 50 percent of breast cancer cases remainunexplained.
The effort to understand and explain the major reasons for today’s excessive level ofbreast cancer has produced an ongoing, unsettled debate with differing findings in theepidemiological and biological research conducted thus far. However, there is asignificant body of evidence to suggest that synthetic chemicals in the environment mustbe factored in as a primary risk for breast cancer.
Within the broad demographic picture, there is a distinguishable relationship between therates of breast cancer and the general use of man-made chemicals. The highest rates ofbreast cancer are found in the industrialized nations of North America and northern Europe, and the lowest are in Asia and Africa. Researchers who looked at the 339 U.S.
counties with hazardous waste sites and contaminated groundwater found consistentlyhigher rates of breast cancer than in counties without such contamination, as reported inthe Archives of Environmental Health in 1989. People who move to industrializedcountries from countries with low breast-cancer rates soon develop the higher rates of theindustrialized country. Young women who emigrate to the U.S. from Asia, where the rateis lower by four-to-seven times, undergo an 80 percent increase in their risk within thespan of a generation. A generation later, the rate for their daughters approaches that ofU.S.-born women.
An estimated 75,000 synthetic chemicals are in commercial use today, two-thirds ofwhich have never been tested for their effects on human health. It is a well documentedfact that chemicals persist in the environment, accumulate in body fat and are carried bywomen in their breast tissue. Studies have identified the presence of dozens of syntheticchemicals in women's breast milk. Indeed, the modern breast has been characterized as a“toxic waste site.” Synthetic Estrogens as “Promoters” of Breast Cancer
A cancer is not a spontaneous creation but is the result of definite chemical and physicalagents. Before a cell reaches a state of full-blown malignancy there is a prelude of threestages: initiation, promotion, and progression. Ionizing radiation is a completecarcinogen. It triggers and promotes cancer, and it also hastens the growth of themalignancy. The female sex hormone estrogen, on the other hand, does not directlyinitiate breast cancer, but rather facilitates or accelerates the disease, according to currentscientific thinking.
Although estrogen is necessary for childbearing and for healthy bones and hearts, it hasbeen established that women who have estrogen active in their bodies for a prolongedperiod -- that is women who menstruate before age 12, do not reach menopause until afterage 55, have children late in life or not at all, do not breast-feed, or who use hormonereplacements after menopause -- are in the category of higher risk for breast cancer. In acollaborative study by the National Institute of Environmental Health Sciences and theTremin Trust Research Program, women with a later menopause, as well as those with alater first pregnancy, had a higher risk of breast cancer risk. In the same study womenwith four or more pregnancies had a far lower risk. In addition, women whose menstrualcycles averaged less than 26 days between bleedings had a 60 percent increase in breastcancer risk compared to women with longer cycles. Women with a greater cumulativenumber of menstrual cycles (more than 350) had about twice the risk as those with fewercycles.
The idea that estrogen can act as a “promoter” of cancer is based on its basic role as achemical messenger. The hormone stimulates the release of proteins called growthfactors, which, in turn, instruct breast cells to divide and specialize. If the cells arehealthy, nothing seems to go awry, but if the cells are already damaged then estrogen may trigger a rapid division, leading possibly to other alterations and resulting ultimatelyin tumors.
The most fundamental evidence showing estrogen as a cancer promoter is seen in animalstudies where breast cancer-causing chemicals do not produce a significant proliferationof tumors unless estrogen is present. In addition, there is the unexpected finding of a1998 study from the London School of Hygiene and Tropical Medicine in which fraternaltwins reported more hormonal cancers than identical twins. Because fraternal twinsreceive above-normal levels of estrogen and other hormones while in the womb, it ispossible they are more susceptible to abnormal cell growth later in life.
In the early 1990s, researchers began to investigate whether chemicals with propertiesthat mimic naturally occurring estrogen, sometimes called xenoestrogens, may alsopromote breast cancer. The research has looked at whether synthetic estrogens add to awoman’s lifetime exposure of estrogen and thereby increase her risk. Researchers havetheorized that living in the midst of a number of widespread and persistent xenoestrogens-- such as Bisphenol-A (BPA), an additive found in the plastic lining of cans that hasbeen shown to leach into canned foods -- may help explain the increase in breast cancerin industrialized countries. Recent research is beginning to bear out this theory.
“Hormone mimickers” belong to a group of chemicals known as organochlorines (anychemical that includes an organic molecule such as carbon, combined with chlorine) andare contained in the makeup of many pesticides, fuels, plastics, detergents andpharmaceutical drugs. Once ingested, they can be stored in body fat for years.
Several studies have shown drastic changes in the development of the reproductivesystem when laboratory mice are exposed to “hormone mimickers” in utero. It appearsthat fetuses and embryos, whose growth and development is highly controlled by theendocrine system, are the most vulnerable to and may have the most lasting effects fromexposure to synthetic estrogens.
In 1993 scientists at Cornell University Medical School made news with their suggestionthat exposure to synthetic estrogen can cause cells to grow rapidly out of control andform tumors. Researchers at Tufts University Medical School subsequently verified thebasic Cornell findings by demonstrating that xenoestrogens can make human breastcancer cells grow in a laboratory setting.
The most convincing evidence that synthetic chemicals can act like hormones andproduce delayed detrimental effects is perhaps the experience with diethylstilbestrol(DES). A strong synthetic estrogen, DES was given to pregnant women in the 1950s and1960s to prevent miscarriages. It was also used in cattle feed to speed growth and time tomarket. Although there was evidence early on that DES was not effective againstmiscarriage, it was not banned until the 1970s after daughters of women who took thedrug were found to have higher reproductive problems and cancer rates than those whowere not exposed to DES in the womb. Laboratory studies on mice have also confirmedthat offspring of DES-administered animals develop reproductive disorders and cancer.
It is thought that a way to link synthetic chemicals to breast cancer is by comparing levels of certain chemicals in the blood of women stricken with the disease to levels in healthywomen. Yet epidemiologists are thwarted, as in the case of a recent Long Island study,when they begin their measurements after the disease has advanced enough to bedetectable because the cancer itself can consume body fat and purge chemicals from awoman’s system, leading to false readings. However, researchers with the BostonUniversity Superfund Basic Research Program, in cooperation with the CopenhagenCenter for Prospective Studies, were able to avoid this difficulty by using a rare bank ofblood samples taken prior to the development of the disease.
During the 1970s approximately 7,500 Danish women aged 30-75 years had bloodsamples taken, a portion of which was frozen and stored, and the Boston Universityresearchers sent these samples to the U.S. Centers for Disease Control and Prevention(CDC) for analysis. Organochlorine compounds were detected in a majority of thesamples from 240 women who subsequently had been diagnosed with breast cancer. Thebanned pesticide dieldrin, a compound that has shown estrogenic activity during in vitroassays, was found in 78 percent of the samples. Women who had the highest levels ofdieldrin years before cancer developed had at least a doubled risk of breast cancercompared to women with the lowest levels. This supports the hypothesis that early-lifeexposure to higher levels of hormone-disrupting pesticides can alter the body's ownproduction of hormones, or in some other way increase the risk of breast cancer.
One predictor of higher risk for breast cancer is the amount of body fat in women whohave passed menopause. Studies of women after menopause have correlated a higherproportion of body fat to higher amounts of free circulating estrogen and an increasedrisk of the disease. This correlation has led some researchers to speculate that a high-fatdiet, common to women of the industrialized world, in and of itself could be responsiblefor their high rates of breast cancer. Other researchers, however, make the point that adiet high in fat is often also a diet highly contaminated with the pesticides and synthetichormones used in industrialized food production. Moreover, body fat attracts and storessome of the worrisome organochlorines contained in pesticides.
On Cape Cod, where nine of 15 towns have breast cancer rates at 20 percent aboveaverage for the state of Massachusetts, researchers at the Silent Sprint Institute arepartway through a study that preliminarily has raised suspicions about industriallyproduced estrogens in the water. The vast sandy beaches of the Cape give the area afragile ecosystem that allows contaminants to seep quickly through porous soil intounderground aquifers. Pesticides used on forests, cranberry bogs, golf courses, and lawnsmake their way into water supplies. In the first stage of the Cape Cod study, reported in1997, chemical estrogens were found in septage, in groundwater contaminated by wasteand in some private wells.
In the Massachsetts town of Newton, Silent Spring Institute researchers also have pointedto "hormone mimicking" compounds in pesticides as a possible way of explaining whybreast cancer is often associated with women of affluence. The researchers surveyed1,350 residents living in areas where breast cancer incidence was either high or low.
They found that women in the high-incidence areas generally had larger disposableincomes and reported regular use of professional lawn services, termite treatments or Several research teams have looked specifically for a connection between breast cancerand the notorious pesticide DDT (dichlro-diphenyl-trichloroethane) or its major break-down product DDE, some of which is stored in body fat, including breast fat. For morethan 30 years, prior to the Environmental Protection Agency’s ban on domestic use ofDDT in 1972, the pesticide was sprayed for control of insects on farm fields and inswampy areas, and it was common for children to run through the chemical mist to cooldown on hot days. The early version of DDT, containing an estrogen-like form calledo,p'-DDT, also reached many homes as a residue on food, a situation that continues tothis day because DDT deteriorates very slowly in the soil and much farmland is stillcontaminated.
While some DDT/DDE studies have shown no correlation to breast cancer when lookingat the blood from women already diagnosed with the disease, a few noteworthy studieshave found above-average levels of the chemicals in women with breast cancer. In acohort of 14,290 women from New York diagnosed with breast cancer within six monthsafter blood samples had been taken, those with the highest concentrations of total DDE(and polychlorinated biphenyls) had a fourfold increase in the risk of breast cancer, asreported by the Journal of the National Cancer Institute in 1993. In addition, one of thepreliminary findings of investigators at the Mount Sinai School of Medicine in NewYork, who are comparing the levels of chemical residues in blood serum samples takenfrom breast cancer patients with those from control subjects with no history of thedisease, is that breast cancer patients have elevated levels of DDT.
In a study of laboratory animals who were fed a combination of DDT and a knowncancer-causing substance, breast tumors appeared sooner than when the animals weregiven the carcinogen alone, suggesting that DDT is another “promoter” of breast tumors.
In other studies the estrogen-like form of DDT enhanced the growth of estrogen-dependent breast tumors. Researchers are also trying to confirm a new finding that DDTmay increase the production and circulation of certain types of estrogens in the blood.
There is additional evidence that simazine, a herbicide that routinely runs off intowaterways after being applied to farmlands in Florida, California and the Midwest, maycontribute to breast cancer in a related fashion. One study has reported an increase ofbreast tumors in female rats that were fed simazine. Researchers are now trying todetermine if simazine changes the levels of hormones in experimental animals in a waythat may affect breast tumor formation. Although simazine-treated animals did not haveelevated levels of estrogen, they did have elevated levels of another hormone calledprolactin, which is known to play a role in the development of breast tumors in animals.
Heptachlor epoxide, an ingredient in insecticides widely used throughout the 1980s, isknown to build up and stay in breast fat. Although heptachlor itself does not act likeestrogen, it does affect the way the body processes estrogen in the liver. It also has beenshown to disrupt cell-to-cell communication in human breast cells in the laboratory.
While growing in the body, cells need to communicate with each other to regulate theirgrowth. By disrupting this growth regulation mechanism, heptachlor could promotebreast cancer. (There is somewhat better evidence that heptachlor can promote liver tumors. Male mice that were given heptachlor simultaneous with water laced withdiethylnitrosamine (DEN), a known carcinogen, were twice as likely to develop livertumors than those given only DEN.) Heptachlor continues to contaminate soil aroundbuildings where it was poured for termite control as well as to contaminate food grownon soil where it was used for crop protection.
Chemicals that either mimic estrogen or that are otherwise hormonally active -- that is,they interfere with normal hormone metabolism -- can be found in many household itemsin pantries or refrigerators, on bedroom vanities, under the sink or on utility-roomshelves. Even when the chemicals are in solid form, there is no guarantee they can besafely stored. For example, the estrogenic chemical bisphenol-A, which alters sexualdevelopment in male lab animals, may be released from food containers made ofpolycarbonate plastics. Polycarbonate is also used to make plastic baby bottles and isfrequently found as a lining in metal food cans.
Phthalates, used to render plastics soft and flexible, are another common householdchemical. They are found in soft plastic “chew toys” marketed for infants and also insome varieties of nail polish, perfumes, skin moisturerizers, flavorings and solvents.
Phthalates are generally toxic to the reproductive system, and many of these chemicalsmimic estrogen. In late 2000 scientists with the Centers for Disease Control reported thatlevels of some phthalates in women of childbearing age, including dibutyl phthalate(DBP), exceed the government’s safety standards. In addition, other solvents such astoluene, an ingredient in many paints, thinners, and glues, are suspected of disruptinghormones.
Chemicals from a variety of sources, including household items, enter the human bodyand contaminate breast milk, the nourishment provided to 60 percent of newborns in theU. S. A comprehensive testing of breast milk is yet to be conducted, but DDT and otherpesticides have been discovered in preliminary searches for contaminants. In Europe,where the research is ahead of the U.S., a common flame retardant has been found atincreasing levels in tests of mother’s milk.
Women are therefore faced with a quandary with regard to breast-feeding. Althoughbreast milk is a source of important nutrients, breast-feeding also transmits undesirableamounts of foreign chemicals and contaminants to the infant. Ironically, this"downloading" of the mother's body burden of foreign chemicals may be one of thereasons why breast-feeding helps lower the mother's risk of breast cancer.
“Good” Mimickers versus “Bad” Mimickers
The prevailing evidence against synthetic estrogens must also be understood in thecontext of other evidence about the qualities of plant estrogens (phytoestrogens), anotherform of estrogen mimickers. Such foods as whole grains, dried beans, peas, fruits,broccoli, cauliflower and especially soy products are rich in these mimickers. Bacterianaturally present in the human intestine apparently change elements in these foods into hormone-like compounds with estrogenic activity that is generally considered beneficial.
Ongoing research indicates that phytoestrogens may offset synthetic xenoestrogens. Inboth human and laboratory studies, plant-based estrogens appear to help reduce awoman's risk of breast cancer. Women in Asian countries who traditionally consumemore soy products than most women in the U.S. have a higher concentration ofphytoestrogens in their blood and urine and a lower risk of breast cancer. Adding soyproducts to the diets of women also has led to lower levels of harmful estrogens in theirbodies compared to women on regular diets. In laboratory research, high concentrationsof genistein, a type of phytoestrogen, can inhibit the growth of isolated breast cancercells.
When laboratory conditions vary, phytoestrogens can produce opposite results. Forinstance, at low concentrations, genistein can be made to stimulate the growth of cancercells in vitro.
However, it is believe that the human body has the ability to gain value from plant-basedestrogens and withstand any negative effect due to the fine-tuning of the body overseveral millennia. It is also known that the digestive system can break down and releasephytoestrogens in as little as a day. Meanwhile, on an evolutionary scale, chemical-basedestrogens are brand-new to the human system, and the body has yet to develop naturaldefenses against them. Consequently, many xenoestrogens lodge inside the body andremain chemically active for decades.
Other Synthetic Chemicals as “Risk Factors” for Breast Cancer
The earlier a woman’s breast begins to grow and the longer it undergoes naturalhormonal activity, the longer it remains vulnerable not only to estrogen-like “promoters”of cancer but also to chemicals that can directly cause cancer.
While the scientific community has undertaken almost no significant research aimed atclarifying whether there are specific links between breast cancer and cancer-causingchemicals, the evidence from other cancer studies strongly implies that links do exist.
Tests performed on laboratory animals -- a standard for public health research --implicate more than 90 chemical compounds in breast cancer formation. Other researchhas demonstrated that chemicals can act synergistically with each other as well as withionizing radiation, creating an effect greater than the sum of the individual effects.
Chemicals can likewise merge into hazardous combinations. Some research, for instance,has suggested that simazine can react with other chemicals to form the chemicalnitrosamine, which is known to increase cancer risk.
Yale University researchers recently reported that women who ate a diet heavy with well-cooked red meat during the three years before diagnosis had three to four times morebreast cancer than those who consumed much less meat. The Yale research raisesquestions about possible dangers from chemical contaminants in the meat, either fat-seeking organochlorines or leached-out ingredients from the plastic used in packaging.
In the late 1980’s, laboratory researchers at Tufts University discovered a mysteriousproliferation of breast cancer cells in cultures that underwent no external stimuli. Theyconcluded that a compound in the plastic culture dishes, made of polyvinyl chloride(PVC), was leaching into the samples. PVC is used extensively in the manufacture offood packaging, as well as in medical products, appliances, cars, toys, credit cards, andrainwear. Extremely toxic, PVC has been linked to liver and breast cancer amongworkers who handle it in the manufacturing process.
The prevalence of PVC in the industrialized world, particularly in items purchased byhigher-income consumers, may constitute a possible explanation for why women in theupper economic strata demonstrate higher rates of breast cancer.
A more specific connection between financial status, breast cancer rates and the chemicalperchlorethylene (PERC), the principal ingredient in solvents used in dry-cleaning, wasmade in the Silent Spring Institute’s Newton, Massachusetts survey. Wearing clothescommercially dry-cleaned was the habit of 45 percent of the Newton women who lived inareas with a high incidence of breast cancer, whereas only 32 percent of those in low-incidence areas regularly took advantage of commercial cleaners. PERC has been linkedby other research to bladder cancer, leukemia, and esophageal cancer.
The highly toxic synthetic chemical compounds known as polychlorinated biphenyls(PCBs) have likewise been identified as carcinogenic in a number of studies. In the NewYork cohort study PCBs, in combination with DDE, were found to be a risk factor forbreast cancer. Although PCBs were banned by the EPA in 1976, as many as two-thirds ofall the insulation fluids, plastics, adhesives, paper, inks, paints, dyes and other productscontaining PCBs remain in commercial use. The other one-third persists in soil, waterand in living tissue.
When PVC or PCBs are burned, one of the chemical elements released is dioxin, a groupof toxic by-products of incineration and other industrial processes that use chlorine. Ofall toxic chemicals, dioxin may be the most prevalent. It is absorbed in the body fat ofevery human being, including every newborn. Within six months of being breast-fed, ababy in the U.S. receives the maximum recommended lifetime dose of dioxin. Primarysources of dioxin are chicken, pork, fish, eggs, beef, milk and other dairy products. Anendocrine-disrupting chemical, dioxin was officially declared a known carcinogen by theEPA in the summer of 2000 after more than a decade of controversy. Although dioxinhas not been conclusively linked to breast cancer, a recent study in England implicateddioxin in the development of mammary tumors in laboratory mice.
Action and More Research Needed
The precautionary principle of science says that when public health is at stake, the burdenof proof for taking action should be a reasonable reading of the evidence rather thanabsolute certainty. By that standard, there is ample proof to take steps toward reducing or,in certain cases, eliminating certain toxic chemical that are omnipresent in the lives of somany women in the modern industrialized world.
In the interim it is important to undertake more research to try to resolve questions that bear directly on these hazards. Of priority is the testing and screening of industrialchemicals and pesticides for their toxicity and hormone mimicking effects; measuringand tracking the body levels of these chemicals in the American public; and investigatinghow girls and women are exposed to these chemicals. Overall, more data needs to becollected and analyzed to examine why the established risk factors increase a woman'svulnerability for breast cancer and whether newly identified risk factors found insynthetic chemicals are also contributing to the epidemic.
This document copyrighted by The Breast Cancer Fund, 2001.
General Research on Breast Cancer Risk
Laden, F., and Hunter, D. J. (1998). Environmental risk factors and female breast cancer.
Annual Review of Public Health 19, 101-123.
Lichtenstein, P., Niels, V., and Pia, K. (July 13, 2000) Cohorts of Twins from Sweden,Denmark and Finland. The New England Journal of Medicine. Vol. 343, No. 2 Millikan, R., DeVoto, E., Newman, B., and Savitz, D. (1995). Studying environmentalinfluences and breast cancer risk: Suggestions for an integrated population-basedapproach. Breast Cancer Research and Treatment 35, 79-89. Swerdlow, A.J., Stavola,B.L., McPherson, K., and Bouletreau P. (1998) Study of cancer in twins. Lancet. Vol.
Whelan, E.A., Sandler, D.P., Root, J.L., Smith, K.R. and Weinberg, C.R. (1994)Menstrual Cycle Patterns and Risk of Breast Cancer. American Journal of Epidemiology,1994; 140: 1081-90.
Whyatt, R. M., Perera, F. P., Jedrychowski, W., Santella, R. M., Garte, S. and Bell, D.A.
(February 2000) Association between Polycyclic Aromatic Hydrocarbon-DNA AdductLevels in Maternal and Newborn White Blood Cells and Glutathione S-Transferase P1 and CYP1A1 Polymorphisms Cancer Epidemiology, Biomarkers &Prevention. Vol. 9, 207-212.
“Overall Evaluations of Carcinogenicity to Humans.” International Agency for Researchon Cancer of the World Health Organization. As evaluated in IARC MonographsVolumes 1-77 Evidence of Estrogenicity
Adami, H., Lipworth, L., Titus-Ernstoff, L., Hsieh, C., Hanberg, A., Ahlborg, U., Baron,J., and Trichopoulos, D. (1995). Organochlorine compounds and estrogen-related cancersin women. Cancer Causes and Control 6, 551-566.
Ahlborg, U. G., Lipworth, L., Titus-Ernstoff, L., Hsieh, C.-C., Hanberg, A., Baron, J.,Trichopoulos, D., and Adami, H.-O. (1995). Organochlorine compounds in relation tobreast cancer, endometrial cancer, and endometriosis: An assessment of the biologicaland epidemiological evidence. Critical Reviews in Toxicology 25, 463-531.
Andersen, H. R., Andersson, A.M., Arnold, S. F., Autrup, H., Barfoed, M., Beresford, N.
A., Bjerregaard, P., Christiansen, L. B., Gissel, B., Hummel, R., Jørgensen, E. B.,Korsgaard, B., Le Guevel, R., Leffers, H., McLachlan, J., Møller, A., Nielsen, J. B., Olea,N., Oles-Karasko, A., Pakdel, F., Pederson, K. L., Perez, P., Skakkeboek, N. E.,Sonnenschein, C., Soto, A. M., Sumpter, J. P., Thorpe, S. M., and Grandjean, P. (1999).
Comparison of short-term estrogenicity for identification of hormone-disruptingchemicals. Environmental Health Perspectives 107, 89-115.
Brody, J.G., Rudel R.A., Melly S.J., and Maxwell, N.I. (1998) Endocrine disruptors andbreast cancer. Forum for Applied Research and Public Policy 13 (3): 24-31 Brody, J.G., Rudel R.A., Maxwell, N.I. and Swedis, S.R. (1996) Mapping out a searchfor environmental causes of breast cancer. Public Health Reports3 (6): 495-507.
Hoyer, A. P., Grandjean, P., Jørgensen, T., Brock, J. W., and Hartvig, H. B. (inconjunction with National Center for Environmental Health) (1998). Organochlorideexposure and risk of breast cancer. Lancet. Volume 352, 1816-1820 Hoyer, A.P., Jorgensen, T. and Grandjean, P. (1998) Breast cancer and dieldrin. Lancet,Volume 356 Issue 9244 Page 1852.
Maxwell, N.I., Polk, R., Melly, S.J., and Brody, J.G. (1999) Newton Breast CancerStudy. Silent Spring Institute.
Robison, A. K., Sirbasku, D. A., and Stancel, G. M. (1985). DDT supports the growth ofan estrogen-responsive tumor. Toxicology Letters 27, 109-113.
Rudel, R.A., Geno, P, Melly S.J., Sun, G., and Brody, J.G. (1998) Identification ofalkylphenols and other estrogenic phenolic compounds in wastewater, septage, andgroundwater on Cape Cod, Massachusetts. Environmental Science & Technology 32 (7):861-869.
Safe, S. H., and Zacharewski, T. (1997). Organochlorine exposure and risk for breastcancer. Etiology of Breast and Gynecological Cancers, 133-145.
Snedeker, S. M., and DiAugustine, R. P. (1996). Hormonal and environmental factorsaffecting cell proliferation and neoplasia in the mammary gland. In Cellular andMolecular Mechanisms of Hormonal Carcinogenesis, J. Huff, J. Boyd and J. C. Barrett,eds. (New York: Wiley-Liss), pp. 211-253.
Soto, A., and Sonnenschein, C. (Tufts University) (1995) E-Screen assay as a tool toidentify esrogens: an update on estrogenic environmental pollutants. EnvironmentalHealth Perspectives, Vol 103 (Suppl. 7): pgs 113-122.
Wolff, M., Zeleniuch-Jaquotte, A., Dubin, N., and Toniolo, P. (2000). Risk of breastcancer and organochlorine exposure. Cancer Epidemiology, Biomarkers and Prevention9, 271-277.
Effects on Cell Proliferation, Cell Cycle and Cell Communication
Bradlow, H. L., Davis, D. L., G., L., Sepkovic, D., and Tiwari, R. (1995). Effects ofpesticides on the ratio of 16a/2-Hydroxyestrone: A biologic marker of breast cancer risk.
Environmental Health Perspectives 103, 147-150.
Brown, N. M., and Lamartiniere, C. A. (1995). Xenoestrogens alter mammary glanddifferentiation and cell proliferation in the rat. Environmental Health Perspectives 103,708-713.
Synthetic Chemicals and Carcinogenic Properties
Adams, N. H., Levi, P., and Hodgson, E. (1990). In vitro studies of the metabolism ofatrazine, simazine, and terbutryn in several vertebrate species. Journal of Agriculturaland Food Chemistry 38, 1411-1417.
Ahlborg, U. G., Lipworth, L., Titus-Ernstoff, L., Hsieh, C.-C., Hanberg, A., Baron, J.,Trichopoulos, D., and Adami, H.-O. (1995). Organochlorine compounds in relation tobreast cancer, endometrial cancer, and endometriosis: An assessment of the biologicaland epidemiological evidence. Critical Reviews in Toxicology 25, 463-531.
Aronson, K., Biller, A., Woolcott, C., Sterns, E., McCready, D., Lickley, L., Fish, E.,Hiraki, G., Holloway, C., Ross, T., Hanna, W., SenGupta, S., and Weber, J. (2000).
Breast adipose tissue concentrations of polychlorinated biphenyls and otherorganochlorines and breast cancer risk. Cancer Epidemiology, Biomarkers andPrevention 9, 55-63.
Awasthi, M. D., and Ahuja, A. K. (1995). Organochlorine insecticide residues in bovinemilk and commercial baby milk powder. Journal of Food Science and Technology 32,420-422.
Bibbo, M., Gill, W.B., Azizi, F., Blough, R., Fang, V.S., Rosenfield, R.L., Schumacher,G.F.B., Sleeper, D.K., Sonek, M.G., Wied, G.L. (1977) Follow-up study of male andfemale offspring of DES-exposed mothers. Obstetrics and Gynecological Journal. 49:1-8, 1977.
Blount, B.C., Silva, M.J., Caudill, S.P., Needham, L.L., Pirkle, J.L., Sampson, E.J.,Lucier, G.W., Jackson, R.J., and Brock, J.W. (October 2000) Levels of seven urinaryphthalate metabolites in a human reference population. Environmental HealthPerspectives. 108(10): 979-982.
Brand, K., Jang, C., Park, J.H., Serrano, P., Weker, R., Lee, K., and Yanagisawa, Y.
(1999) Residual Perchlorethylene in Dry-cleaned Acetate: The Effect of Pressing andExtent of Inter Dry-cleaner Variability. Journal of Air and Waste ManagementAssociation, Air and Waste Management Association, Pittsburgh, USA, 49, pp 213 – 218 Brown, N.M., et al (1998) Prenatal TCDD and predispoisition to mammary cancerin rats. Carcinogenesis Vol. 19, No. 9, 1623-1629.
Dich, J., Zahm, S. H., Hanberg, A., and Adami, H.-O. (1997). Pestcides (heptachlor) andcancer. Cancer Causes and Control 8, 420-443.
Epstein, S. S. (1976). Carcinogenicity of heptachlor and chlordane. Science of the TotalEnvironment 6, 103-154.
Greenberg, E.R., Barnes, A.B., Resseguie, L., Barrett, J.A., Burnside, S., Lanza, L.L.,Neff, R.K., Stevens, M., Young, R.H., and Colton, T: (1984) Breast cancer in mothersgiven diethylstilbestrol in pregnancy. New England Journal of Medicine. 311:1393-1398.
Griffith, J., Duncan, R.C., Riggan, W.B., and Pellom, A.C. (1989) Cancer mortality inU.S. counties with hazardous waste sites and ground water pollution. Archives ofEnvironmental Health. (:) 44:69-74.
Lahvis, G. P., Wells, R. S., Kuehl, D. W., Stewart, J. L., Rhinehart, H. L., and Via, C. S.
(1995). Decreased lymphocyte responses in free-ranging Bottlenos dolphins (Tursiopstruncatus) are associated with increased concentrations of PCBs and DDT in peripheralblood. Environmental Health Perspectives 103, 67-72.
Longnecker, M. P., Rogan, W., and Lucier, G. (1997). The human health effects of DDT(dichlorodiphenyl-trichloroethane) and PCBs (polychlorinated biphenyls) and anoverview of organochlorines in public health. Annual Review of Public Health 18, Rogan, W. J. (1996). Pollutants in breast milk. Archives of Pediatric and AdolescentMedicine 150, 981-990.
Stevens, J. T., Breckenridge, C. B., Wetzel, L. T., Gillis, J. H., Luempert III, L. G., andEldridge, J. C. (1994). Hypothesis for mammary tumorigenesis in Sprague-Dawley ratsexposed to certain triazine herbicides. Journal of Toxicology and Environmental Health43, 139-153.
Wolff, M.S., Toniolo, P. G., Lee, E.W., Rivera, L.M., and Dubin, N. (1993) Blood levelsof organochlorine residues and risk of breast cancer. Journal of National CancerInstitute. 85: 648-52.
Zheng, T., Holford, T., Mayne, S., Tessari, J., Ward, B., Carter, D., PH, O., Boyle, P.,Dubrow, R., Archibeque-Engle, S., Dawood, O., and Zahm, S. (2000). Risk of femalebreast cancer associated with serum polychlorinated biphenyls and 1,1-dicrholoro-2,2'-bis(p-chlorophenyl)ethylene. Cancer, Epidemiology, Biomarkers and Prevention 9, 167-174.
Zheng, T., Holford, T., Mayne, S., Ward, B., Carter, D., Owens, P., Dubrow, R., Zahm,S., Boyle, P., Archibeque, S., and Tessari, J. (1999). DDE and DDT in breast adiposetissue and risk of female breast cancer. American Journal of Epidemiology 150, 453-458.
Properties of Phytoestrogens
Kuiper, G. G. J. M., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag,P. T., van der Burg, B., and Gustafsson, J. A. (1998). Interaction of estrogenic chemicalsand phytoestrogens with estrogen receptor beta. Endocrinology 139, 4252-4263.
Jean-Christophe Bier Erasme Hospital, Department of Neurology Residency in various departments of Internal Medicine, Erasme Hospital, Brussels followed by six months of residency in the department of Neurology, Ambroise Paré Hospital, Mons, Belgium, 1995-1996 Neurological residency in the department of Neurology, Erasme Hospital, Université Libre de Neurologist in the department of Neurolo