Document 8O2vKw4paq019B5MnyMbVw3Ro

^ . . a between breast cancer, exposure to comnion chemicals The most striking study to dote, pub lished in April by Mary Wolff of Man hattan's Mount Sinai Medical Center, found that women whose blood con tained high concentrations of residues from the banned pesticide DDT -- n known estrogenic chemical -- were four times as likely to get breast cancer os woman with low concentrations in their blood, Breast cancer risk rose steadily as the level of DDT residue in creased, Wolff found. A cascade of research linking estro genic chemicals and breast cancer -- in cluding the insecticide beta-HCH and the electrical insulators known as PCBs -- has captured the attention of the na tion's cancer research establishment, which has traditionally spurned envi ronmental studies and focused instead on treatment techniques and genetics. When it published the Wolff study, the -Journal of the National Cancor In stitute editorialized that the research " may have extraordinary global impli cations for the prevention of breast cancer" and should serve "as a wnkcup call for urgent research." "The environmental hypothesis is extremely interesting and scientifically important, and we're going to pursue it," said Dr. Samuel Broder, director of the National Cancer Institute. "This is an area that is certainly high priority, and it's very important to me personal ly." Broder said he has a special reason to be interested: his wife has breast can cer, and her sister died of the disease; both grew up in a Bellmore neighbor hood where breast cancer Seemed un- usually common, he said. trogenic chemicals, especially pesticides "It's a high priority for us. and par that are used on fond crops, toxicologists ticularly for NCI," agreed his boss, Sec at the U.S. Environmental Protection retary of Health and Human Services Agency say too little is understood about Donna Shalala. "We're going to aggres estrogen-linked cancer to make regula sively pursue and put'resources into tory drisions. The evidence isn't even breast cancer, and we're going to focus strong enough, they say, to justify on prevention." screening pesticides to determine which Many, scientists remain skeptical. mimic natural estrogen. They emphasize that As a result, few pesti there is no one cause of cides have been tested to the disease, and suggest see whether they are es that genes or diet or some ns-yct-unidentified B ttE A S T trogenic. Even for the 15 pesticides that have been factors may be more im shown to. cause breast C i t E f tportant than estrogenic chemicals. If pesticides cancer in rats the EPA does not require test for were so significant, they argue, epidemiologists would have proven by A S p e c ia l R epo r t estrogenicity. And not one of those pesticides has been banned by the now that breast cancer risk is higher in areas where exposures to es T hird In a series on the disease EPA, even though the agency has banned doz ens ofpesticides for caus trogenic chemicals are a n d Its to ll o n LI ing other types of cancer high. in mice or rats. "T h e more I read Coming Tuesday: "We're still so early in about the breast cancer Examining the possible the process of figuring issue, the more confused links between past out what's happening in I get," said John McCar pesticide use, the human population, thy, chief scientist with Li's drinking water and understanding the the National Agricultur and breast cancer horm onal m echa al Chemicals Associ n ism s," said K arl ation, the pesticide in The Series So Fer Baetcke, an EPA toxicol d u s tr y 's t r a d e J une 27:Afb Llers at ogist who has wnrkcd association. "It's clear greater risk? Study e x te n s iv e ly on th e that the experts are all finds an average breast cancer issue. "I over the map as to what's cancer risk but really have no confi causing breast cancer." higher death rate. dence that we're going While some scientists J ult 25; Fran and Jerry to make trem endous are already calling for Lenzo's Story. strides in the next few tough restrictions on es years in how we deal with mammary tumors." Despite the EPA's uncertainty, mo mentum in the srientificcommunity is shifting as other theories fall by the wayside. Studies have largely discredit ed the oncc-popular idea that a high-fat diet increases breast cancer risk. And Tor all the fierce competition among ge neticists seeking to become the first to identify the breast cancer susceptibility gene, that gene is so unusual that it is believed responsible for only one in 20 breast cancer cases. Earlier this year, the National Can cer Institute announced it was moving ahead with more than a dozen research rejects on environmental factors and reast cancer, including a multimilliondollar effort that will look closely at women on Long Island and elsewhere in the Northeast. "All of a sudden, everybody is out there now trying to show there are a lot of chemicals in the environment that could cause breast cancer," said Louise Brinton, chief of the environmental studies section at the cancer institute and a breast cancer specialist. Those links are still unproven, she said, but ore "provocative and worth pursuing, because there is a plausible biological mechanism behind the association." Putting the Pieces Together Like a l,000*piece jigsaw puzzle thnt suddenly becomes recognizable when it's almost finished, the toxics-based theory of breast cancer has been con structed from an assortment of seem- Pleasesee PESTICIDES on Page 72 NEWSDAY, SUNDAY. SEPTEMBER Scientists used (a think that cells kn ow n a s estrogen receptors function like locks that can only be opened b y estradiol, a natural horm one. Higher, estradiol levels raise the risk o f b re ast c a n c e r b e c a u s e , w h e n it is 'o p e n e d ,* a receptor is believed to . s -- \ natural t r i g g e r 11 f o \ --tjo g o n proliferation ^ . ) (estradiol) breast. New studies focus on link'' First o f two parts By Dan F agin / staff w riter CCads ommon pesticides are now emerging as key suspects in explaining the dramatic three-decade rise in the incidence of breast cancer. Increasing evidence suggests that a growing number of chemicals that kill insects, stifle weeds and even lubricate condoms are also able to mimic the effects of estrogen, B u t now researchers have discovered that the *keys' carried b y D O T an d certain other synthetic ch e m ica ls c a n als o o p e n the rec ep tor 'fe c k s ,* .1*.- suggesting that higher levels o f tho se chem icals In Ihe b o d y m ay m e a n higher breast cancer risk. r . ' . ....... : - DDT (or other '> natural .f A s y n th e tic estrogen-----h O \ estrogenic r a M . (estradiol) ) I c h e m ic a ls) JgM g& l O V (l y o 0 ^0 Q More celi proliferation Higher m ger Atht ethgersoaumpe otimf heo, nrmewosntuedsieassasroecailasoted ewstriothgehnsig? hWehrybarreena'st twceatnryciengr rtiosrke. directly linking some of these chemicals duce exposures?" said toxicologist to breast cancer Tor the first time. Devra Lee Davis. A senior adviser to the:, Yet despite growing excitem ent U.S. assistant secretary for health, Da-* among scientists about these research vis is a key architect of the theory that' discoveries, federal regulators so fur the synthetic chemicals she calls ''xeno-' hove moved slowly-- fat all -- to cata estrogens" are a preventable cause of logue these chemicals or to restrict breast cancer. their use. They say it may be years be Even the most ardent advocates don't fore they understand estrogen-linked contend that a woman who is exposed to cancers well enough to justify bans or an estrogenic chemical issomehow fated special testing. to dovelop the disease. But they doassert As a result, no pesticide has ever that mure exposure means mure risk, been banned for causing breast cancer, and that the proliferation of synthetic even though ut least IS have been chemicals over the past few decades shewn to cause breast tumors in rats -- helps explain why the odds that an* including the top-selling pesticide in American woman will gel breast cancer the nation, utrozine. Another lid indus by age 85 have skyrocketed, from one In trial chemicals huve also been found tn 20 in I960, tu one in eight today. cause breast tumors in nits or mice, In its effort to explore this volatile Newsduy found in a review uf Todera! issue, Nowaday obtained thousands of records and scientific literature, but pages of federal documents under the human exposure to those chemicals' Freedom of lnfonmitiun Act, inter generally is lower than to pesticides. viewed dozens of officials and experts, These are the principal findings uf a and reviewed the latest scientific re-' Ncwsday examination uf envinanmen search. tal factors and breast cancer, a baffling potential killer that will strike a record 180,000 American women this year, more than any other kind of cancer. The disease'3 origins arc largely a mystery. Known risks explain only 30 percent of all coses. Out there ia an im portant clue; all of the proven risks ex cept family history are traceable to high lifetime exposure to estrogen, the family of hormones that regulates female sex ual development. Women who have their first child lute in life for example, or who begin menstruating early, are more likely to get breast cancer. TTiesa are a m o n g th e m o s t w e ll-. know n c o m p o u nd s that are suspected to bind w ith estrogen receptor ceils. O f this g ro u p , D O T an d P C B s have been experim entally linked to breast ca n cer tn h u m a n s :. Now, surprisingly, scientists are dis covering that a-number of pesticides that have been routinely used in back yards'and farm fields also can trigger cell proliferation and biochemical changes tHaPare similar to changes in human cells caused by natural estro gen. And some of those estrogenic chemicals, which can accumulate in hu Chla nla n # A termite-killer that ' , ' Kopona U se d as bait In an t a n d : ' ; w a s u s e d n e a r fo u n d a tio n s o f 30 ~ i co ckro ach traps until it w a s b a n n e d m illlonhom esbeforaltw asbanned '.-lril9 78 . .. In 15 8 8 . . - j ...- ., H e tfu q e h lo r AnIrjsocticfdestill D D T T h e w o i i t f s lea din g ' (u s e d on trees a n d s o m a ve g e ta b le s . * : insecticide unto It w a 3 b a n n e d In * r- HonyJphflnol A c o m m o n the U nited S ta te s In 1 9 7 2 , it Is still : Ingredient o f plastics, in d u s tria l' Eressnt In s o m a soils a n d in th e *'' de te rgents, c o n d o m lubricants a n d . io o d 3trearns o f virtually all spermicidal cream s. Am ericans. , P C B s (polychlorinated D la d n A byproduct o f w aste .. biphenyls): Electrical insulators,' incineration, ft la also an In g r e d ie n t' ; th e y were b a n n e d in 1 9 7 8 b u t are , tn sevsral n e w -b a n n e d p e s tic id e s .. still fo u n d tn old transform ers a n d in . H ap tae h lo r A termite-killer, it. soil, water, animals and p e o p le ., w as banned In 1978.- man fatty tissue for decades, are now being linked to breast cancer in people and not just rats. If those studies are confirmed, it would mark the first time that a direct environmental cause has been estab lished Tor breast cancer, and the focus of the nation's multimillion-dollar bat tle against breast cancer could shift to prevention, instead of only diagnosis and treatment. "It seems* quite obvious, doesn't it? There's only one common thread tying together all ofthe known risk factors for breast cancer: the more estrogen exposure'in a woman's lifetime, the greater * . *r: '.t'> tier risk of breast cancer. So why aren't we looking hard at these environmental nkhiifd lliir fii Jr.1 chemicals that we now know tan'act like NEWSDAY, SUNDAY. SEPTEMBER 6, IBM I" Studies Probe the Pesticide I'K SnCinES from Page 5 ingly unconnected observations and ex periments tliat have boon assembled gradually nvur thu years. 'I'he first clues came from DOT. In "Silent Spring" -- published in 1BU2, a I decade before the insecticide was banned -- Rachel Carson described how birds (including Long Island ospreys) of ten couldn't reproduce utter being ex posed lu DDT because of the paper-thin shells of Ihe eggs they laid, a function regulated by estrogen. And by thu midH)70s. evidence was emerging that DDT uttdPLns interfere with a mother's abil ity to produce milk for breast feeding, another estrogen-regulated function. Meanwhile, breast cancer research ers were nuLicing that estrogen seemed to figure prominently in most aspects of the disease. They didn't knuw why -- and still aren't sure today -- but higher i lifetime estrogen exposure seemed to mean higher breast cancer risk. In the lab, experiments were showing that breast tumors in laboratory rats subsided when the rats' ovuries (the source of natural estrogen) were re moved, hut returned when the rats were injected with estrogen. And surveys of women were showing that the ones who were exposed to un usually high levels ofestrogen were also more likely to got breast cancer. Having thu first child late, menstruating early, entering menupause late, and using ear' ly high-dose versions of oral contraccp`lives and estrogen-replacement ther apies all incruase lifetime exposure to nuturjl estrogen -- und all were being * revealed as risk factors far breast can ` It seems quite obvious, doesn't it? . . . So why aren't trigger the same chemical reactions in the body that are caused by natural es trogen. But, according to the prevailing scientific view, chemicals developed for other purposes couldn't possibly trigger the same estrogenic reactions. we looking hard at these A Surprising Discovery environmental chemicals that The prevailing view wus wrong. By the mid-1980s researchers hud devel we now know can act like oped ways to screen chemicals to see if they acted like natural estrogen,' and estrogens? Why aren't we began discovering that several synthet ic chemicals were estrogenic, including trying to reduce exposures?' PCBs and Ihe pesticides DDT, betuIICH, chlordune, Kepane and methox- --Devra Davis, U .S. Health Dept, toxicologist ychlor. At least one was identified by acci dent: nonylphenol, a common plastics additive that's also used in condom lu cer. Women whose ovaries were surgi selves: if estrogen is a key to breast can bricants, spermicides and industrial de cally removed, or who entered meno cer, but naturally produced estrogen tergents. It was discovered when a pause at an early ago, were found to be less likely to get breast cancer. But there wereothorcuriosities about breast cancer that could not be ex plained by the body's own estrogen. For one thing, all those known risk factors plus family history could be linked to only about 30 percent of all breast can cer eases. What's more, the disease's in cidence begun surging in the decades after World War II even though women during those years were having more children than before and were giving birth at an earlier age. And finally, epi demiologists noticed that breast cancer is fur rarer among women in Japan, but that thu children of Jupanese women cannot fully explain the disease's re blood sample was found to be unexpect lentless frequency, what can? edly estrogenic, arid the problem wus Synthetic chemicals were the obvious eventually traced back to plastic tubing suspect, because of what happened that had tainted the blood. when chemists created an extremely powerful estrogen called DES, or dieth ylstilbestrol. The drug was prescribed to millions of pregnant women to pre vent miscarriage during the 1950s and 1960s, until researchers realized that daughters of these women were having extraordinarily high.rates of vaginal and cervical cancer. DES has not been linked to significantly higher breast Of that group, all have been banned except nonylphenol and methoxychlor, 'which is still sprayed on fruit trees on Long Island and elsewhere. But even those chemicals that have been banned -- all for health reasons that have nothing to do with estrogcnicity -- are still ofton present in soil, water or in the tissues of people and animals. So far, fewer than 100 chemicals have been tested for estrogenieity. But some cancer risk in humans, but when scien researchers believe scores of common tists gave it tn ruts, the animals almost chemicals may eventually be identified inevitably developed breast tumors. as estrogenic because those that have who immigrate to the United States face DES was a triumph-turned-tragedy been discovered to date are so diverse. ihcsame risk asother American women. of chemical engineering, a compound " iL's really quite strange, but there So researchers began to ask them that had been designed specifically to are new [estrogenicl chemicals emerg- Scientist Who Made the DDT Link Groundbreaking study stunned researchers Mary WolITdoesn't took, act or talk like a revolu An associate professor of community medicine tionary. at Mount Sinai School of Medicine, Wolff, 50, The scientist chooses her words with the same works in a cramped, windowless office in upper |. cautious precision that she applies to her work, Manhattan, where she does the meticulous work of the measurement of human exposures to toxic analyzing blood and tissue samples for minute chemicals. traces of toxic chemicals. But her study linking breast cancer risk to the For the past two years, she has been looking for banned insecticide DDT had a revolutionary effect DDE, a product of the breakdown of DDT. The when it was published in April in the Journal of the insecticide has hcen banned since 1972, but it is so National Cancer Institute. The study is by far the persistent in the environment that DDE residues strongest evidence yet that toxic chemicals may be are present in virtually all Americans, where it an important cause of breast cancer, and it has set accumulates in fatty tissue, oITa scramble as researchers around the world seek She studied frozen blood samples from 58 New to replicate her flndingaor find other chemicals that York area women who appeared healthy but would also may increase breast cancer risk. be diagnosed with breast cancer within six months "The Wolff study is very interesting and pro after the blood samplo was taken, and compared vocative. It's generated, a lot of new work," said them with bluod front 171 women who were demoSheila Zuhm, an epidemiologist at thu National graphically similur to the 58 in every way except Cancer Institute. "Within a year or two years that they remained cancer free, there's going to bo a lot of new information.'' . Her conclusion: Women were four times as like "There's certainly a lot more excitement in this ly to get breast cancer if they had very high levels area now that the Wolff study is out,''agreed Lou of DDE in their blood than if they had very low ise Brinton, chief of the environmental studies sec levels. tion ut the cancer institute. "We're, all trying to The study's biggest drawback is that it was rela figure out what to do next." tively small, and that's why Wolff is now expand Activist groups like Greenpeace are already us ing her study by analyzing a larger number of ing Weld's research to argue far a broad phase-out blood samples for DDE. of all chlorine-based organic chemicals -- a huge Once that's finished, she said, she hopes to take family of synthetic compounds that includes many part in a much larger environmental study that the pesticides that are chemically similar to DDT and cancer institute is preparing to launch of breast thus might be linked to breast cancer. cancer risk in the Northeast, including Long Island. But Wolff refuses to draw such sweeping conclu "As I've always said, this may or may hot hold up sions based on her work. "Until the data are con in future studies," Wolffsaid, "But if nothing else,' firmed time after time it's not goingto be considered it will force breast cancer epidemiologists to look at other potential causes. Up to now, there just hasn't been much of Uiat going on." . -- Dan Fagin  ' .*$ BRIASTCANR ON U ing'in th e literature almost every month now," said John McLachlan, sci entific director of the National Insti tute of Environmental Health Sciences and a hormone specialist. "Based on what we know now, it wouldn't bo sur prising ifthere area lot of them." Even though they had begun identi fying the suspects, however, scientists still didn't hove solid evidence that syn thetic estrogens actually cause breast cancer in humans. The only linkages had been tenta tive. Two years ago, a Finnish research team found thnt a pooled blood sample from 44 women with breast cancer had 50 percent more beta-HCH, an estro genic insecticide, than blood, from a control group of cancer-free women. And last year, a Connecticut study found that malignant breast tissue from 20 women contained more than twice as >much PCBs and DDT residue as a control group. Both studies had a serious flaw: Nei ther was designed to factor out the known risk factors for breast cancer. The women could have gotten cancer not because of exposures to PCBs or DDT, but because the disease ran in their family or because they started menstruating early or had children late. Or, by another thcoiy, the breast tumors could somehow have led to higher blood levels of the toxic chemi cals, instead of vice versa. So when one of the collaborators on the Connecticut study, Wolff of Mount Sinai Medical Center, set out to do an other study, she carefully selected her subjects from among almost 15,000 New York-area women who had gotten mammograms at Now York University' between 1985 and 1991. Those women had filled out detailed questionnaires and given blood samples, which were then frozen for preservation. Wolff decided to analyze the frozen blood samples of 58 women who had no sign of breast cancer at the time their blood was drawn, but were diagnosed one to six months afterward. She matched up those 58 women with 171 others who remained cancer-free but were virtually identical to the 58 in age, childbearing history and virtually every other characteristic known to influence breast cancer risk. What WoIfTfound startled her. PCB concentrations were 15 per cent higher in the bloddf'Of women who would later develop cancer, and DDT residues were 35 percent higher. But what was most surprising is Lhat breast cancer risk rose steadily a3 the level of DDT residue increased. In fact, the 10 percent of women with the highest amount of DDT residue in their blood were four times as like ly to get breast cancer as the 10 per cent with the lowest. That would make DDT one of the most powerful risks for breast cancer ever identified. Stronger than a history of benign hreost disease, or a close rela tive with breast cancer. Stronger than late menopause, early menstruation, or late childbirth. Stronger than being white, or wealthy, or Jewish or living in the suburbs. "The numbers are terrifying, really. I still can't believe the risk is that Please see PESTICIDES, Next Page .1. ,U, .UU-JlilAWJJ'UWfF JJ1CW4W An Estrgen Explainer What It IS. A group o f horm ones that cause the growth an d developm ent of fem ale sexual characteristics in hu m a ns and other anim als. T h e b o d y m akes three principal form s o f estrogen: estrone, estradiol a n d estriol, Estriot Is the m b s h p o tja n f a n d plentiful."' !? T h e increased a m o u n t o f e s tro g e n In ' the bloodstream causes developm ent o f breasts, maturation of the reproductive tract and the appearance , of secohdary sexual characteristics. Estrogen regulates the menstrual cycle and stimulates the lining o f the uterus to thicken. A t puberty a young w om an's ovaries begin to secrete estrogen In response to stim ulation from the folide-stlmulating horm one (FS H J produced b y he pituitary gland. > ! Ovaries Uterus Estrogen Levels A post-puberty and pre-m enopausal w om an with a norm al m enstrual cycle secretes ab ou t 70 to 500 m icragrams of estradiol a d a y depending on the phase ol her m enstrual cycle. aA s w o m a n g ro w s o ld e r her ovaries secrete (ess e s tro g e n . After m enopause estrogen production declines, bones becom e m ore fragile an d risk o f heart attack rises. > j, r i'.u.'t n >,1 I ,in. .iiri} 11 V'.:> I r I ,t i' ' ' i n ' f'vt / r r,*i'vf i V ' , Nowaday / iNelii-irl IInrrt J r A Q&A: What Can You Do To Cut Your Risk By Dan Fagin associated with increased STAFF WRITE(1 breast cancer risk. However, The most important thing current formulations contain women can do to reduce their risk far less estrogen, and links to of dying from breast cancer is breast cancer are inconclusive to detect the disease early -- at best. The best policy is to through breast self- discuss both the risks and examination, good medical care benefits with your doctor. and, for women over ngc 40, yearly regular mammograms. But when it comes to (J: Will eating right reduce my risk? avoiding bi-enst cancer in the first A: Probably. There are many place, there arc frustrntingly good reasons to stick to a low-fat, few things women can do that arc proven to cut their risk, because most of the disease's known risk factors are beyond control. Still, experts say there nro prudent steps women can take thnt might reduce their risk, and are worth doing anyway because of other health benefits. Here's a sampling of the experts' advice: high-fiber diet rich in vegetables -- and avoiding breast cancer might be one of those reasons. A high-fat diet has not been proven to be a risk factnr Tor breast cancer, but obesity is a proven risk. It's possible thnt overweight people are at greater risk because some carcinogenic chemicals are attracted to Tatty tissue and accumulate there. Qucstinn: If I avoid pesticides, But that has not been proven. will I reduce my risk of gelling There's also some evidence breast cancer? that women shouldn't scrimp on Answen There's no easy vegetables like broccoli, answer to thnt question. There are spinach, carrot3 and sweet hundreds of common pesticide potatoes that are rich in beta- formulations on the market, each carotene, which the body converts with unique characteristics and to Vitamin A. Thnt's important benefits. And there's no proof that because Vitamin A is known to any or them cause breast cancer have a regulating effect on cell in humans. On the other hand, formation, and therefore perhaps many are associated with on cancer. health problems in animals and people. So a general polio'of avoiding unnecessary pesticide exposures is advocated by many experts. And when you do use them be sure to strictly follow precautions on the label. Pesticide exposures should not be considered a reason to avoid eating fruit and vegetables, however. The health benefits of a balanced diet far outweigh any risk that might be associated with pesticide residues. Of course, The cruciferous family of vegetables -- including cabbage, cauliflower, broccoli and brusscls sprouts -- may be especially beneficial because they contain tndole-3-carbinol. The body metabolizes naLural estrogen in two ways, but only one of thorn is associated with higher breast cancer risk. Indole3-carbrnol has been shown to stimulate the safer mule of metabolism. it's always a good idea to wash vegetables and fruit before eating them. Q: What about drinking alcohol? A: Even moderate drinking is (1: What about pesticides and known to increase the risk of * other synthetic chemicals that are breast cancer, and heavy estrogenic -- that mimic the drinkers/ncc an even higher risk, effects of natural estrogen? No one is sure why, hut it may A: That depends on whom you be because alcohol recently has ask. The evidence is still been shown to raise estrogen inconclusive, but some levels in premenopausal women. scientists believe exposure to On the other hand, there is estrogenic chemicals may be an important risk factor for breast cancer. Few chemicals have been screened for estrogenicily, but many may eventually be shown to be estrogenic because they cause breast cancer or other hormone-related problems in animals. some evidence that having one or two drinks a day -- but no more -- lowers the risk of cardiovascular disease, which kills more women than breast cancer. While there are many preventive actions women can take that might reduce their Q: Should I stop taking birth- risk of breast cancer, experts control pills, or stop participating emphasize the most important in estrogen replacement thing is to diagnose the disease as therapy? early as possible. The American A: Not necessarily. In the early days of the pill and of estrogen Cancer Society recommends women 40 to 49 get replacement therapy! both mammograms every one or two relied on high doses Of estrogen, i ^ear^; and yearly m am m ogram s, and both eventually were . . . *' f . LM- i (: , f ! H. |sscntjal fpq jvnpcn.gver 50. () t MEWSOAY,1SUNDAY. SEPTEMBER 5. 74 REAST CANCER ON LI Pesticide Peril: Studies Probe PESTICIDES from Preceding Page high," WolfTsaid, WoIfTs study was relatively small, but its findings were enough to set oft a flurry of research as scientists seek to replicate her results, or find similarassocialions between other synthetic es trogens and breast cancer. The pace quickened in May when another study found that heavy alcohol use, one of the few strong risks that had not been linked to estrogen, did indeed lead to. higher estrogen levels in women. And other research has found that women actually face a lower risk of getting breast cancer when they are exposed to the toxic chemical dioxin, which lowers estrogen levels instead of raising them. ``There's a line of research now that is really coming together from very broad fields," said Davis, the toxicol ogist, who Is collaborating on an on going study that she said will identify new estrogenic chemicals. "Up to now, we've tended to focus our efforts in the wrong place. . . . We have tended to assume that because estrogen is a hor monal thing, a women's thing, there's nothing we can do about it except say, 'Oh dear, oh my.' In fact, what we now know is that a number of environmen tal chemicals can act like estrogens." The EPA at a Standstill , The cose against estrogenic pcsth tides isn't conclusive, but some scien tists believe it's far enough along tojus tify special action by the agency responsible Tor protecting Americans from unsafe pesticides: the EPA. There are two controversies associtrd with the EPA's performance on pes ticides and breast cancer. First, the agency doesn't screen pesti cides for estrogen!city, or impose restric tions on pesticides that have been iden tified as estrogenic by someone else.. Second, after debating the issue for almost a decade, EPA officials haven't decided what to do about pesticides that have been proven to cause breast cancer in rata. In both cases, the agency's position is rooted in what the EPA says is a lack of solid scientific information about how estrogenic chemicals actually cause cancer. T h e more I read about the breast cancer issue, the more confused I get. It's clear that the experts are all over the map as to what' s causing breast cancer.' --John McCarthy, chief scientist, National Agricultural Chemicals Association The notion that estrogen could be a pathway to cancer is an entirely newone for the EPA, which is much more famil iar with the conventional idea that chemicals cause cancer by directly at tacking genes. And there are other com plications, too, including uncertainty over whether breast tumor in rats arc comparable to human breast cancer. "We just don't understand what the hormonal mechanism is, so the agency is really in a quandary as to what the heck do we do about this," said one EPA toxi cologist, who asked not to be identified. The EPA's stance dismays some re searchers and activists, many of whom advocate a phase-nut o all chlorinated organic chemicals, a huge family of compounds that includes most of the known synthetic estrogens. "What we've seen so far from the EPA is very discouraging," said Theo Col burn. a World Wildlife Fund biologist. "We have got to get into a preventive mode and begin looking for these [hor- monall effects ahead of time, instead of waiting until it's too late and these pro ducts are already in the environment," Other scientists say the regulatory focus should be on pesticides that are used on food crops, particularly those that are attracted to fatty tissue and can build up in body fat over decades. "If you've got a chemical that bioac cumulates and is estrogenic, then I think you have to think very hard about whether you want to put it on the market and for what reason," said Ana Soto, a cell biologist at Tufts University who developed one of the first estrogenicity screening tests. "No one is talking about getting rid of all these chemicals and going back to the Middle Ages, but rather to be able to detect problems be fore we release these chemicals into the environment." Davis agrees. "Something that is es trogenic, attracted to fat and stored in the body, ought to be treated very strict ly and probably ought not to he used unless it is Torn critical national purpose and there is no substitute," she said. At the very least, some researchers say, the EPA should require that all pesticides be systematically screened to see if they are estrogenic. "From the standpoint of public health, I think it's very important to know" which arc estrogenic, said McLachlan, the scientific director of the National Institute of Environmen tal Health Sciences. Screening pesticides to see if they are estrogenic is not particularly expensive or complicated, according to Soto and others who have developed the tech niques. The cost to manufacturers would be far less, they say, than that of the health and safety tests the EPA al ready requires. But agency officials argue that the scientific evidence is not yet strong enough to justify screening and special restrictions. "It would be nice to know" which pesticides are estrogenic, said Penelope Fenner-Crisp, chiefof the health effects division in the EPA's pesticides office. "But you've got to remember that we don't have free license to tell people to go out and generate data just because something's titillating our intellect." In addition, the EPA and the pesticide industry say special rules aren't needed because the EPA already requires test ing on rats and mice. If a pesticide is estrogenic, they say, the effects presum ably would be detectable through such symptoms as unusual organ weights, re productive disorders, and breast, testi cular or uterine tumors. "Even though we don't do estrogenic screening, we would pick up whether or not there's estrogenic activity through the basic pathology that we do on these animals," said McCarthy, of the indus try trade group. Under EPA rules, pesticide manufacturersare required to test their products on 50 mice and 50 rat3 over a two-year period, and to compare the results to a similarly sized control group. If any thing unusual is found in the animals, the manufacturer is supposed to report it to the EPA, which then calculates the ' * risk that the pesticide poses to people and the noturol environment. Balanc ing that calculation against the econom ic benefits ofa pesticide, the agency then decides whether to ban it, restrict it to certain doses or crops, orcertify it con be used without restriction. ~ That's the way the process is sup posed to work anyway. But when the health issue posed by a pesticide is breast cancer, EPA records shnw, the agency has been unable to make a decision. And under federal law, when the EPA doesn't decide, pes ticides can stny in the marketplace. Records obtained by Newsday under the Freedom of Information Act show that the EPA has designated only 10 chemicals as breast carcinogens in rats, and not one hns been banned or re stricted on that basis. Four have been banned or withdrawn for other reasons and the agency is still trying to figure out what to do about the other six. In fact, while the EPA has identified only 10 pesticides as breast carcinogens in rats, the actual number may be high er. The National Toxicology Program, Another Target: Electromagnetics By Dan Fagin STAFF WRITER There's another mainstay of the industrial age, besides estrogenic chemicals, that is getting in creasing attention in breast cancer research: elec tromagnetic fields. Reported associations with childhood leukemia and brain tumors have gotten more attention, but electromagnetic Helds have been inconclusively linked to breast cancer in at least four epidemi ological studies. And unlike links to leukemia and brain cancer, there is a biologically plausible explanation for an association with breast cancer. The explanation is estrogen, the common thread that ties together all of breast cancer's known risk factors except family history. Scientists know that melatonin, a hormone manufactured during nighttime darkness by the pineal gland in the brain, plays a key role in inhib iting production of estrogen. They also know that sustained exposure to electric fields, or to light during night houre, interrupts melatonin produc tion. JVheri ftielaWnin levels are depressed, estro-* gen levels rise, On the other hand, those studies were all rela "Nobody can imagine how this would work for tively small, and did not try to factor out other leukemia and brain cancer, but with breast cancer risks such a3 age or alcohol use. And several other we have the estrogen pathway, and it makes a lot studies that hare looked for links between use of of sense," said Scott Davis, an epidemiologist at electric blankets or electric bed heaters and brenst University of Washington at Seattle. Studies have consistently shown that when rats are fed a carcinogenic chemical and then exposed to constant light or to electric fields, they develop breast tumors faster and more frequently than rats that are fed the chemical but not exposed to the fields. And laboratory research has shown that when melatonin is added to human breast cells in a Petri dish, cell proliferation slows dramatically. What's still lacking is solid evidence ofan associ ation between electromagnetic fields and human breast cancer. At least four studies have found some evi cancer have found no association. By far the biggest and best-designed study on the subject was launched this summer in Seattle. With a -$3 million grant from the National Cancer Institute, Scott Davis is surveying 800 tool wom en with breast cancer, and 800 healthy women who closely resemble them in age, childbearing history and other known risk factors for breast cancer. Light and electric fields will be measured inside each of the womens' bedrooms, and-so will appli ances and power lines near their homes. Some of the women will cany meters to measure their ex dence of higher-than-expected rates of male posures throughout the day. breast cancer among electric power workers, By next summer, Davis said, he hopes to have telephone linemen and electricians. Male breast completed the measurements and begun looking cancer is extremely rare, so it's easier to notice for associations between electric field exposures . devitaituiuoinias fnruoim easier to stjudy. the normal rate, and TMiiui n :e v luldi tts'It is thus and breast cancer i ; ^ f ion?hiE (Ini 11 oJ I n ? I ` riak. "We're going to see if the >1(111, II " i J i h " 1tfpi! -f! 1 i:*t 'lir'ie . Jli:*'!'Y d isl* I e d l T l l i i t . 1 o ; r rrt'ii NEWSQAY. SUNDAY. SEPTEMBER 9. 1993 I 75 lin' example, has identified at least five'additional Mure than 70 million pounds of the weed-killer pesticides that cause breast cancer in rats, after will be used this year, mtislly on corn, grains, fruit, testing a lew dozen of the more than 700 pesticides and occasionally lawns. Atropine is now regularly on the market. That program is conducted by fed turning up in rivers and streams in the Midwest, eral researchers at the National Cancer Institute and scientists studying a corn-growing region of and the National Institute or Environmental northern Italy have reported that women exposed Health Sciences. to utrazine arc twice as likely to get ovarian cancer. The reason the EPA may be overlooking some Why is it taking so long for the ugcncy to figure pesticides is that the agency, unlike' the National out what to do about atrazmo and the other pesti Toxicology Program, relies on a particular type of., cides linked to breast cancer? rat called the Sprague Dawley that has d naturally1 A lot of reasons, EPA officials say. high rate of breast cancer. As some agency toxicol- The most fundamental explanation is that while ngists privately acknowledge, that means many the EPA occasionally moves swiftly when the evi- chcmicals that may cause breast cancer may have dcnce is overwhelming, Ihu agency typically takes been missed by the EPA because it's difficult'to tell years to make any regulatory decision, ifa chemical is raisingtho rat's nuturally highrate "Obviously, the program has taken a terrible of breast cancer even higher. ' ' beating on the speed of the review process," said the And there's another piece of evidence that the EPA's Fenner-Crisp. "Unfortunately, we have EPA may bo overlooking some breast carcinogcris' some examples of it taking a decade or more." Most of the information on the cancer risks of pes? Out agency officials say there are other issues tickles comes from manufacturers or from th e ' that arc unique to breast cancer: reliance on a rat EPA evaluation of their tests. But for industrial that has high background levels of breast cancer, chemicals that arc not pesticides, most of the test- " and uncertainty over whether estrogenic effects in mg is done by other federal and academic research- rats are comparable to people. When u pesticide . induces tumors in some other organ `The environmental of the rat -- the liv er or stomuch, say hypothesis is extremely -- that discovery typically is a major interesting and scientifically factor when the agency decides how important, and we' re going to to regulate the pes ticide. The EPA pursue it. This is an area that generally assumes that if a pesticide is certainly high priority.1 causes cancer in rats, it also poses a -- Dr. Samuel Broder, director, risk to people, be cause most car th National Cancer Institute cinogenic p e sti cides arc thought to cause cancer by damaging genes -- era. And those studies have found that breast tu a route to cancer that is relatively well understood, mors are a pervasive result of chemical exposures. and thought to be similar in people and rats. At least 68 non-pesticide chemicals -- many of But the EPA ho3 been at a loss over what to do them structurally similar to pesticides -- have about the breast tumor results in rats because those been identified by federal or private researchers os cancers are thought to be caused by an estrogencausing breast cancer in lab animals, according to delated process that's poorly understood, and might lists compiled by and for Newsday. That's more not be compurublo to humans. chemicals than have been linked to any other kind of cancer except liver, lung and stomach. In the few cases when the EPA has concluded that a pesticide causes breast cancer in rats, the agency has not acted on the information. Of the 15 pesticides that have been identified so. Tar as causing breast cancer in rats, several have been banned or withdrawn -- but always for other reasons. This group includes four of theEPA-tden- Another complication is that if estrogen is the path from pesticide exposure to breast cancer, some scientists believe there may be a minimum thresh old ofexposure to the chemical that must be exceed ed before there is significant cancer risk. CibaGeigy is currently trying to prove to the EPA that a hormonal threshold exista for atrazine, although so far the agency has not accepted that view. "You can't just do a simple extrapolation and lifiod pesticides: captafol, propazine, terhutryn say that since you found tumors in the rat, you're und Savey. And it also includes all five of the pesti going to find them in humans," said Darrell Sum cides identified by the National Toxicology Pro ner, a toxicologist with Ciba-Geigy. Except for the gram: 1,2-dichloropropane, l,2-dibromo-3-chloro- propane (DBCP), 1,2-dichloroethane, sulfallate und l,2-dibromoethane(EDB). -y But six other pesticides that the EPA has offi cially designated as breast carcinogens in rats re main on the market: atrazine, cyanazine, express, Sprague Dawley rat, he said, breast tumors have not been found in any other animals exposed to atrazine. And there's laboratory evidence that atrazine may actually suppress estrogen produc tion instead of stimulating it, he said. The issues are so complex that a year ago, the oryzalm, simazine and terrazole. And only atra EPA convened a special panel of outside scientists zine and simazine face any restrictions at all. Both can be applied on farms only by certified pesticide applicators, although homeowners ore still free to use them without restriction. Because it's so widely used, atrazine is perhaps to look at the question of whether the breast tu mors in the Sprague Dawley rat are really compa rable to human breast cancer. However, that panel has met only three times in the past year, and its members say a final report the most striking example of the EPA's indecisive* may not be issued for several more years. And even ncss on breast cancer. when the report is finally issued, the panel is un It's been nine years since the agency learned that likely to take a firm position on the question, atrazine causes breast tumors in rats, the pesti 1`We're really stuck, because we'rejus t beginning cide's only known carcinogenic effect, EPA records show. Those tests were conducted by a firm hired by atrazine's manufacturer, Ciba-Geigy Carp., and EPA memos indicate the agency considered those tests particularly persuasive because they showed that the higher the dose ofatrazine, the more likely a rat was to get breast cancer. By 1988, the EPA had formally declared atrazine a mammary carcinogen to learn about the mechanisms that lead to cancer," said Hugh Spitzer, associate director of the Insti tute of Life Sciences International, the nonprofit group the EPA hired to direct the panel's work. But despite all the uncertainties, Spitzer argues that scientists ought to assume that the rat is a good surrogate for people unless proven otherwise. "Until you can lay out tho very definitive differ in rats, and a possible human carcinogen. ences, you shouldn't walk away from those tumors, But today, the EPA still hasn't decided what to . . . I fuel very strongly about that.'' l X " S E i 5 f i E < ''`T te 3,; pK eldM,b ,e3 St r idling juiijidu in the United States. and Long Island's drinking water. Newiday/Jlm Peppier A Iemale Sprague Dawley ral Now, Some Smell a Rat A white rat that tends to get breast cancer is at the conter of the debate aver what to do about pesticides linked to the disease. The rat is called the Sprague Dawley, and its pedigree is so classy that the nation's research lab- ' oratories buy them by the thousands -- spending about $5 to $7 per rat. The Sprague Dawley is prized by cancer re searchers because it has been meticulously bred to be extremely sensitive to carcinogenic chemicals, which means scientists don't have to test huge numbers of rats before they know whether a chemical causes cancer. Just as important, the rats tend not to get tu mors unless they are exposed to a carcinogen. If ' they're left alone, they stay healthy. Those two qualities have helped make the Spra gue Dawley the most commonly used rat in labora tory research, and a mainstay of the U.S. Environ mental Protection Agency's pesticide testing program. But there's a problem with the rat; breast can cer. Even if they aren't exposed to a cancer-causing chemical, about half the female rats will develop breast cancer before they die. That hasn't been much of an issue in the past; researchers' generally have paid little attention to breast cancer in animals, focusing instead on liver, 3tomach and other kinds of tumors. For most of those other cancers, the Sprague Dawley has usual ly been considered a good surrogate for humans. But as evidence begins to surface linking pesti cide exposures to breast cancer, EPA officials are realizing that hundreds of pesticide evaluations that are based on tests in Sprague Dawley rats might not tell the whole story. On the one hand, the Sprague Dawley may not be a good predictor of human breast cancer risk because the rat is so prone to breast tumors, and that's one reason the EPA hasn't been able to de cide whether to slap restrictions on pesticides that cause tumors in the rat. "There just is not sufficient evidence to know how good a model the Sprague Dawley is for u n derstanding human breast cancer," said David Neumann of the Institute of Life Sciences Interna tional, a nonprofit scientific group that is studying the issue for th EPA. But on the other hand, the EPA may have over looked many carcinogenic chemicals because it's so difficult to tell whether a chemical exposure is rais ing the number of breast tumors beyond an al ready high background level. "Generally, the breast tumors have been disre garded as an effect because the background level is so high you can't tell what's going on," said one agency scientist, who asked not to be identified. Switching to a differentkind ofrat has never been considered, he said, because hundreds of pesticides >wptfR then have o be fltesfcd. 1a , fi*, SUNDAY. SEPTEMBER 51951