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#574 - The Truth About Breast Cancer -- Part 4, 26-Nov-1997

Late last month the NEW ENGLAND JOURNAL OF MEDICINE (NEJM) published a
study (by David J. Hunter) comparing the levels of DDE and PCBs in the
blood of two groups of women, one group with breast cancer, the other
without.[1] The Hunter study failed to find a positive relationship
between breast cancer and DDE or PCBs in the blood. DDE is a breakdown
product of the organochlorine pesticide DDT, which was banned in the
U.S. in the mid-1970s; PCBs are a group of 209 chlorinated industrial
chemicals, also banned in the U.S. The Hunter study is the largest of
its kind to date, comparing 236 pairs of women for DDE and 230 pairs
for PCBs.

The NEW ENGLAND JOURNAL OF MEDICINE put a far-reaching title on the new
study: "Plasma Organochlorine Levels and the Risk of Breast
Cancer." (Plasma is the part of the blood that contains fat-soluble
chemicals such as organochlorines.) The title seemed to suggest that a
study of two chemicals --DDE and PCBs --could tell us something
definitive about all of the 15,000 different organochlorine compounds
in relation to breast cancer.

In case we missed the message, the editors of the JOURNAL provided an
editorial that spelled it out. The editorial, by Stephen H. Safe, a
Texas researcher whose work is often funded by the Chemical
Manufacturers Association, had a slightly different though equally far-
reaching title: "Xenoestrogens and Breast Cancer." (Xenoestrogens are
industrial chemicals that interfere with normal sex hormones such as
estrogen.)

Dr. Safe's editorial in NEJM began, "Chemophobia, the unreasonable fear
of chemicals, is a common public reaction to scientific or media
reports suggesting that exposure to various environmental contaminants
may pose a threat to health." Surely this is an odd message from a
scientist. He is saying, if you fear chemicals because scientific
reports indicate that they might harm your health, you are suffering
from an irrational phobia. Perhaps Dr. Safe did not write the editorial
in his capacity as a scientist.

Dr. Safe concludes his chemophobia editorial saying it is time we all
stopped worrying about organochlorines and breast cancer. He writes,
"The results of Hunter along with those of other recent studies should
reassure the public that weakly estrogenic organochlorine compounds
such as PCBs, DDT and DDE are not a cause of breast cancer."[2]
Estrogenic organochlorine compounds such as DDT, DDE and PCBs are not a
cause of breast cancer. Case closed.

If we still didn't get the point, Gina Kolata of the NEW YORK TIMES
interviewed Dr. Safe, giving him an opportunity to amplify his message.
Dr. Safe told Ms. Kolata it is time to quit researching the
relationship between organochlorine chemicals and breast cancer: "For
advocates [of the idea that the two are connected], it's never ending.
But for other people, there may be times when we want to spend our
money on other things," Dr. Safe said.[3] No more research needed. Case
closed.

Three days later in the Sunday TIMES, Gina Kolata delivered the message
once again, summarizing the Hunter study this way: "One more
environmental scare bit the dust last week as scientists from the
Harvard School of Public Health reported that their large and
meticulous study found no evidence that exposure to the chemicals DDT
and PCB's [sic] are linked to breast cancer."[4] Another scare bit the
dust. Case closed.

Including the recent Hunter study, there are now 11 published studies
of organochlorine compounds (DDE, PCBs, methoxychlor, beta-
hexachlorocyclohexane, and chlordane --the last 3 being pesticides) in
relation to breast cancer. Four studies, including the largest two of
the 11, have shown no relationship between DDE, PCBs and breast cancer.
[1,5,6,7] Six smaller studies have indicated a positive relationship,
suggesting that some organochlorines may be implicated somehow in
breast cancer.[8,9,10,11,12,13] One additional study was equivocal,
subject to differing interpretations.[14]

The equivocal study was by led by Nancy Krieger, who examined DDE and
PCB levels in the blood of 150 women with breast cancer and 150 women
without breast cancer. The 300 women were chosen to represent
racial/ethnic groups: 100 whites, 100 African-Americans and 100 Asian-
Americans. Taken together, the 300 women showed no statistically-
significant relationship between DDE, PCBs and breast cancer. However,
when the racial/ethnic groups were studied individually, the whites and
the African-Americans with breast cancer showed elevated levels of DDE
in the blood, compared to whites and African-Americans without breast
cancer.[14] Asian and recently-immigrated Asian-American women tend to
have a much lower incidence of breast cancer than white Americans,
perhaps because of a protective effect from their diet.[15,16] Omitting
the Asian-Americans from the Krieger study essentially reverses the
study's conclusions.

Thus out of 11 studies, 4 are negative and 7 show elevated levels of
organochlorines of one kind or another in tissues of women with breast
cancer. One of those seven were not statistically signficant. Is it
time to close the book on this inquiry?

Stephen Safe and Gina Kolata obviously want us to think so. Dr. Safe
and Ms. Kolata both try to make us believe that recent work has
revealed that breast cancer can be completely explained by "known risk
factors." Listen to Dr. Safe: "Robbins and coworkers recently showed
that the high incidence of breast cancer in women from the San
Francisco Bay area can be accounted for by known risk factors,
including parity [how many children they've had], age at first full-
term pregnancy, months of breast-feeding, age at menopause, age at
menarche [when a woman's period commences], and alcohol
consumption."[2] Ms. Kolata takes the argument even further: "Dr.
Hunter said that perhaps it was time to question the assumption that
much breast cancer is caused by unknown environmental agents. A recent
study, for example, found that the high rate of breast cancer in the
San Francisco Bay area can be completely attributed to known risk
factors like a woman's age when she start to menstruate, has a first
child, and when she begins menopause."

Dr. Safe and Ms. Kolata both make it sound as if this new study of
women in San Francisco has revealed that all breast cancer can be
explained by "known risk factors." If true, this is important news.

In fact the Robbins study of women in the San Francisco Bay area did
not even try to explain the origins of all breast cancer.[17] Robbins
observed that white women near San Francisco Bay have a 14% higher
incidence of breast cancer than the national average (and African-
American women in the Bay area are 10% above the national average), and
he set out to see if he could explain the 14% and 10% increases. He and
his coworkers found that women in San Francisco tend to have fewer
children, have them later in life, breast feed them less, and so forth,
thus explaining the 14% and 10% increases by "known risk factors." The
50% to 70% of breast cancer that can't be explained anywhere else in
the U.S. also can't be explained in San Francisco --despite the false
impression that Dr. Safe and Ms. Kolata managed to create.

What about Stephen Safe's conclusion (amplified by Ms. Kolata), that,
based on four negative studies of DDE and PCBs, we should stop trying
to find the links between environmental estrogenic chemicals and breast
cancer?

Stephen Safe knows that DDE is not estrogenic. DDT is estrogenic, but
DDE is not. DDE is a potent anti-androgen (it blocks the action of male
hormones).[18] DDE DOES interfere with sex hormones, but it doesn't
mimic estrogen and there's no good reason to think it would make a
major contribution to breast cancer. Likewise, many PCBs are not
estrogenic --on the contrary, they are ANTI-estrogenic. Dr. Safe's own
research has shown this again and again.[19] Thus there is no good
reason to think that DDE and a randomly-selected group of mixed PCBs
will cause breast cancer. Listen once more to Dr. Safe's editorial
(titled "Xenoestrogens and Breast Cancer"). He writes, "The results of
Hunter along with those of other recent studies should reassure the
public that weakly estrogenic organochlorine compounds such as PCBs,
DDT and DDE are not a cause of breast cancer." But DDE is not
estrogenic, and neither are many PCBs. This is a false argument and Dr.
Safe --and the editors of the NEW ENGLAND JOURNAL OF MEDICINE --know
it.

There are good, strong reasons to think that many estrogen-mimicking
chemicals, some of them organochlorines, might be associated with
breast cancer, and these should be carefully examined. But DDE and
mixed PCBs are not in that category. They have been studied because
they are convenient to study, not because they are particularly
estrogenic. When Stephen Safe tells Gina Kolata we might want to end
research on organochlorines and breast cancer based on studies of DDE
and mixed PCBs, Dr. Safe is sounding like a camp follower of the
Chemical Manufacturers Association, not like a scientist.

--Peter Montague (National Writers Union, UAW Local 1981/AFL-CIO)

=====

[1] David J. Hunter and others, "Plasma Organochlorine Levels and the
Risk of Breast Cancer," NEW ENGLAND JOURNAL OF MEDICINE Vol. 337, No.
18 (October 30, 1997), pgs. 1253-1258. Studied 236 pairs of women for
DDT levels and 230 pairs of women for PCB levels.

[2] Stephen H. Safe, "Xenoestrogens and Breast Cancer," NEW ENGLAND
JOURNAL OF MEDICINE Vol. 337, No. 18 (October 30, 1997), pgs. 1303-
1304.

[3] Gina Kolata, "Study Discounts DDT Role in Breast Cancer," NEW YORK
TIMES October 30, 1997, pg. 26.

[4] Gina Kolata, "DDT and Breast Cancer," NEW YORK TIMES November 2,
1997, pg. 2.

[5] M. Unger and others, "Organochlorine compounds in human breast fat
from deceased with and without breast cancer in a biopsy material from
newly diagnosed patients undergoing breast surgery," ENVIRONMENTAL
RESEARCH Vol. 34 (1984), pgs. 24-28. Studied 32 cases and 56 controls.

[6] Pieter van't Veer and others, "DDT (dicophane) and postmenopausal
breast cancer in Europe: case-control study," BRITISH JOURNAL OF
MEDICINE Vol. 315 (July 12, 1997), pgs. 81-85. Studied 265 cases and
341 controls.

[7] Lizbeth Lopez-Carrillo and others, "Dichlorodiphenyltrichloroethane
Serum Levels and Breast Cancer Risk: A Case Control Study from Mexico,"
CANCER RESEARCH Vol. 57 (September 1, 1997), pgs. 3728-3732. Studied
141 cases & 141 controls; 562 ppb for cases, 505 for controls, but not
statistically significant.

[8] Frank Falck, Jr. and others, "Pesticides and Polychlorinated
Biphenyl Residues in Human Breast Lipids and Their Relation to Breast
Cancer," ARCHIVES OF ENVIRONMENTAL HEALTH Vol. 47 No. 2 (March/April,
1992), pgs. 143-146. Studied 20 cases and 20 controls. A dose-response
relationship was observed.

[9] Mary S. Wolff and others, "Blood Levels of Organochlorine Residues
and the Risk of Breast Cancer," JOURNAL OF THE NATIONAL CANCER
INSTITUTE Vol. 85, No. 8 (April 21, 1993), pgs. 648-652. Studied 58
cases and 341 controls. A dose-response relationship was observed.

[10] Mirjana V. Djordjevic and others, "Assessment of chlorinated
pesticides and polychlorinated biphenyls in adipose breast tissue using
a supercritical fluid extraction method," CARCINOGENESIS Vol. 15, No.
11 (1994), pgs. 2581-2585. Found elevated levels of DDE, PCBs,
chlordane, oxychlordane and transnonachlor in breast tissue of 5 women
with breast cancer vs. 5 women without rhe disease.

[11] H. Mussalo-Rauhamas and others, "Occurrence of Beta-
Hexachlorocyclohexane in Breast Cancer Patients," CANCER Vol. 66, No.
10 (November 15, 1990), pgs. 2124-2128. Studied 44 cases and 33
controls. Found that Finnish women with elevated levels of beta-
hexachlorocyclohexane, a breakdown product of the pesticide Lindane, in
their breast tissue had a 10-fold increased risk of breast cancer. See
also, Rosemary Steinmetz and others, "Novel Estrogenic Action of the
Pesticide Residue Beta-Hexachlorocyclohexane in Human Breast Cancer
Cells," CANCER RESEARCH Vol. 56 (December 1, 1996), pgs. 5403-5409.

[12] Eric Dewailly, "High Organochlorine Body Burden in Women With
Estrogen Receptor-Positive Breast Cancer," JOURNAL OF THE NATIONAL
CANCER INSITUTE Vol. 86, No. 3 (February 2, 1994), pgs. 232-234.
Studied 20 cases and 17 controls. Found a nine-fold increased risk of
breast cancer among women with estrogen-responsive breast tumors

[13] M. Wassermann and others, "Organochlorine Compounds in Neoplastic
and Adjacent Apparently Normal Breast Tissue," BULLETIN OF
ENVIRONMENTAL CONTAMINATION & TOXICOLOGY Vol. 15, No. 4 (1976), pgs.
478-484. Organochlorine compounds (DDT and PCBs) were higher in 9
breast cancer patients than in 5 controls, and in cancer patients the
cancerous tissue contains significantly more organochlorines than
adjacent normal tissues.

[14] Nancy Krieger and others, "Breast Cancer and Serum
Organochlorines: A Prospective Study Among White, Black and Asian
Women," JOURNAL OF THE NATIONAL CANCER INSTITUTE Vol. 86, No. 8 (April
20, 1994), pgs. 589-599. In the same issue, see the editorial, pgs.
572- 573 and "DDT and Breast Cancer: The Verdict Isn't In," pgs. 576-
577.

[15] A.H. Wu and others, "Tofu and risk of breast cancer in Asian-
Americans," CANCER EPIDEMIOLOGY, BIOMARKERS AND PREVENTION Vol. 5, No.
11 (November 1996), pgs. 901-906.

[16] Herman Adlercreutz, "Phytoestrogens: Epidemiology and a Possible
Role in Cancer Protection," ENVIRONMENTAL HEALTH PERSPECTIVES Vol. 103,
Supplement 7 (October 1995), pgs. 103-112.

[17] Anthony S. Robbins and others, "Regional Differences in Known Risk
Factors and theHigher Incidence of Breast Cancer in San Francisco,"
JOURNAL OF THE NATIONAL CANCER INSTITUTE Vol. 89, No. 13 (July 2,
1997), pgs. 960-965.

[18] William R. Kelce and others, "Persistent DDT metabolite p,p'-DDE
is a potent androgen receptor antagonist," NATURE Vol. 375 (June 15,
1995), pgs. 581-585.

[19] For example, see M. Moore, S. Safe, and others, "Antiestrogenic
Activity of Hydroxylated Polychlorinated Biphenyl Congeners Identified
in Human Serum," TOXICOLOGY AND APPLIED PHARMACOLOGY Vol. 142 (1997),
pgs. 160-168.

Descriptor terms: new england journal of medicine; breast cancer; dde;
ddt; pcbs; david j. hunter; studies; estrogen; organochlorines; stephen
h. safe; chemical manufacturers association; gina kolata; methoxychlor;
beta-hexachlorocyclohexane; chlordane; nancy krieger;