Here's the editorial from NEJM:
Xenoestrogens and Breast Cancer
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. The specter of cancer, birth defects, and
irreversible effects on infants and children invariably scares people and leads to
demands for action. During the past five to six years, there has been widespread
scientific debate and media coverage concerning a new potential threat to human health
-- environmental exposure to chemicals with endocrinologic activity. Attention has
focused primarily on the weakly estrogenic organochlorine pollutants, including
commercially produced chemicals such as polychlorinated biphenyls (PCBs), the
pesticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT), and its stable
breakdown product 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE). Both PCBs
and DDE are persistent environmental contaminants that have been identified
throughout the global ecosystem, including in fish, wildlife, and human tissue, blood,
and milk. Some have suggested that organochlorine xenoestrogens and related
compounds contribute to the increased incidence of breast cancer in women, a
worldwide decrease in sperm counts and male reproductive capacity, and
neurodevelopmental deficits in children. (1,2,3)
Specific compounds have been linked to various health problems, including cancer, as
a result of occupational exposure to high levels of these chemicals; however, scientific
evidence of adverse effects of low-level environmental exposure to chemicals is difficult
to obtain and validate. In order to link environmental exposure to a toxic or
carcinogenic effect there must be correlations between the level of exposure and the
magnitude or incidence of the response, consistent results from several studies, biologic
plausibility based on results of studies in laboratory animals, and if possible, evidence
based on high levels of exposure in humans.
In 1993, Wolff and coworkers (4) analyzed DDE and PCB levels in serum samples
from 58 women in whom breast cancer was diagnosed within six months after
enrollment in the New York University Women's Health Study. In this nested
case-control study, the mean (+/-SD) DDE and PCB levels were 11.0+/-9.1 and
8.0+/-4.1 ng per milliliter, respectively, in patients with breast cancer and 7.7+/-6.8
and 6.7+/-2.9 ng per milliliter in controls. Further analysis showed a fourfold increase
in the risk of breast cancer as DDE levels increased from 2.0 ng per milliliter (10th
percentile) to 19.1 ng per milliliter (90th percentile). The authors concluded that "these
findings suggest that environmental contamination with organochlorine residues may be
an important etiologic factor in breast cancer" and that "the implications are
far-reaching for public health intervention worldwide."
Previous studies included relatively small numbers of patients with breast cancer, and
the correlations with organochlorine levels were variable. The correlations reported
between DDE levels and breast cancer attracted national media coverage and
contributed to the belief that exposure to industrially derived xenoestrogens was a risk
factor for breast cancer in women. (5) This hypothesis is one reason that Congress
recommended that the National Cancer Institute initiate studies of clusters of breast
cancer on Long Island and in the Northeast.
Although the degree of exposure to estrogens over a lifetime is known to be a risk
factor for breast cancer, the biologic plausibility of the xenoestrogen hypothesis can be
criticized on several counts. (6,7,8) Most of the organochlorine pollutants, including
PCBs and DDT or DDE, are only weakly estrogenic, and these compounds can both
exacerbate and protect against mammary cancer in laboratory animals. High levels of
exposure to DDT have not previously been associated with an increased risk of breast
cancer, and there is no increase in the risk of breast cancer among women who are
exposed to relatively high levels of PCBs at work. (8) Moreover, the incidence of
breast cancer has increased in industrialized countries over the past 20 years, but the
environmental levels of most organochlorine contaminants have decreased as a
consequence of strict regulations regarding their use and disposal. In addition, the
average diet contains very low concentrations of antiestrogenic organochlorine
compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), and higher levels of
naturally occurring estrogenic and antiestrogenic compounds, which are abundant in
fruits, nuts, and vegetables.
In this issue of the Journal, Hunter and coworkers (9) report on blood levels of DDE
and PCBs in women with breast cancer and matched controls from the Nurses' Health
Study, which includes 121,700 women from 11 states. The mean (+/-SD) level of
DDE was 6.01+/-4.56 ng per milliliter in 236 women with breast cancer and
6.97+/-5.99 ng per milliliter in their matched controls, and the mean level of PCBs was
5.08+/-2.51 ng per milliliter in 230 women with breast cancer and 5.16+/-2.26 ng per
milliliter in controls. After extensive analysis, the authors concluded that their "data do
not support the hypothesis that exposure to DDT and PCBs increases the risk of
breast cancer."
Krieger and coworkers (10) used a nested case-control design to study serum DDE
and PCB levels in 150 patients with breast cancer (50 white, 50 black, and 50 Asian
women) from the San Francisco Bay area, another high-risk area for breast cancer,
and matched controls. Serum levels of DDE and PCBs were not significantly different
in the two groups, and the investigators concluded that their data "did not support the
hypothesis that exposure to DDE and PCBs increases the risk of breast cancer."
A recent European study (11) compared DDE levels in adipose tissue in 265
postmenopausal women with breast cancer and 341 controls from centers in Germany,
the Netherlands, Northern Ireland, and Spain. The mean DDE levels were 1.35
micrograms per gram of tissue in patients with breast cancer and 1.5 micrograms per
gram in the controls. Again, the conclusion was that the study "does not support the
hypothesis that DDE increases risk of breast cancer in postmenopausal women in
Europe."
Serum or adipose-tissue levels of DDE are relatively low in North American and
European women because DDT has been banned for over 20 years. This has not been
the case in all countries. In Mexico DDT is still used as an insecticide, and
environmental levels of DDE are higher than in the United States. A recent study (12)
reported that mean serum levels of DDE in 141 patients with breast cancer from three
referral hospitals in Mexico City and 141 age-matched controls were
562.48+/-676.18 and 505.46+/-567.22 parts per billion, respectively. These values
are not significantly different, and the investigators concluded that the findings "do not
lend support to the hypothesis that DDT is causally related to breast cancer at body
burden levels found in our study population."
Robbins and coworkers (13) 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, age at first full-term pregnancy, months of breast-feeding, age
at menopause, age at menarche, and alcohol consumption. It is possible that the
confirmed clusters of breast cancer on Long Island and in other regions of the
Northeast (14) may also be explained by known risk factors. The results of Hunter et
al. (9) along with those of other recent studies (10,11,12) should reassure the public
that weakly estrogenic organochlorine compounds such as PCBs, DDT, and DDE are
not a cause of breast cancer. The public has a right to be responsibly informed about
both confirmed and hypothesized threats to health, particularly from environmental
exposure. However, it is incumbent on scientists, the media, legislators, and regulators
to distinguish between scientific evidence and hypothesis, and not to allow a "paparazzi
science" approach to these problems.
Stephen H. Safe, D.Phil.
Texas A&M University
College Station, TX 77843-4466 |
