Epidemiology of Breast Cancer and Serum Organochlorine and Serum Organochlorine Compounds and Breast Cancer on Long Island
American Health Foundation, New York, NY
Dr. Steven D. Stellman, of the American Health Foundation, New York, NY, and colleagues conducted a hospital-based case-control study to investigate risk for breast cancer in relation to levels of organochlorine compounds, such as DDT and polychlorinated biphenyls (PCB). For the study, women were recruited who were being treated at North Shore University Hospital, Manhasset; Long Island Jewish Medical Center, New Hyde Park; and Bassett HealthCare, Inc., which serves Schoharie County, an area included in the Congressional mandate for breast cancer research on Long Island. About half of the women who participated in the North Shore University Hospital/Long Island Jewish Medical Center component of the study were residents of Long Island.
Long Island Component
Findings from the North Shore University Hospital and Long Island Jewish Medical Center study component were reported in November 2000. Following is the text of a fact sheet from the American Health Foundation that describes the findings:
American Health Foundation
Long Island Study Finds
Little Evidence that
Findings from a hospital-based case-control study of women from Long Island suggest that increased risk for breast cancer does not appear to be associated with past exposure to organochlorine compounds, according to Steven D. Stellman, Ph.D., M.P.H., of the American Health Foundation (AHF), Valhalla, NY, and colleagues. The lack of association held for both women whose tumors were estrogen receptor positive, as well as for women whose tumors were estrogen receptor negative.
The research findings are consistent with the results of other recent investigations of organochlorine compounds and risk for breast cancer that have been reported in other regions. "No single study is definitive; rather, it is the gathering of evidence from different studies and populations that is necessary to reach a conclusion about whether these compounds are associated with increased risk for breast cancer," said Dr. Stellman. "Other research is under way on Long Island that is examining environmental exposures to organochlorine compounds in relation to risk for breast cancer, and we look forward to the findings from these analyses next year."
The findings are reported in the November issue of Cancer Epidemiology, Biomarkers & Prevention.* Collaborating on the study are: Mirjana V. Djordjevic, Ph.D., Joshua E. Muscat, Ph.D., and Lin Gong, Ph.D., of AHF; Julie A. Britton, Ph.D., Mount Sinai School of Medicine; Marc L. Citron, M.D., and Erna Busch, M.D., ProHEaltH Care Associates, Lake Success, NY; and Margaret Kemeny, M.D., State University of New York (SUNY) at Stony Brook, Stony Brook, NY Dr. Stellman is also on the Epidemiology faculty at the Mailman School of Public Health, Columbia University, NY
The study included 232 women who had surgery for breast cancer (cases) and 323 women who had surgery for non-cancerous breast disease or for conditions unrelated to the breast (controls). Of the cases, 199 had invasive breast cancer and 33 had carcinoma in situ. The women in the control group had had surgeries involving their gall bladder, removal of lipomas, abdominal hernias, osteoarthritis, and other conditions unrelated to the breast. The women were treated between 1994 and 1996. Both groups were similar in education, race, body mass index (a composite measure of weight and height), age at first live birth of a child, and county of residence.
The women had received their care at Long Island Jewish Medical Center, New Hyde Park, NY, and North Shore University Hospital, Manhasset, NY, which are the two largest hospitals serving the Long Island population. Fifty-seven percent of cases (128 women) and controls (186 women) lived in Nassau or Suffolk County. The other study participants lived in New York City, primarily in Queens County. There were no major differences in levels of the organochlorine compounds and PCBs when the data were compared between women living in Nassau and Suffolk counties with residents of Queens County. Also, no significant differences in exposures were seen between residents of Nassau and Suffolk counties.
The study participants provided adipose (fatty) tissue obtained at surgery, blood samples, and answered a questionnaire about their medical and reproductive history, diet, smoking, and other lifestyle factors. Adipose tissue was used for this analysis because the fat-soluble organochlorine compounds accumulate and are stored in body fat for many years. They are excreted very slowly from the body, making it possible to look for evidence today of exposures that have occurred over a long period. The adipose tissue from the breast cancer patients was obtained prior to chemical or radiation treatment for the disease.
The study focused on 7 organochlorine pesticides and 14 congeners (types) of PCBs. The organochlorine pesticides or their products measured were: DDT and two related chemicals, DDD and DDE (the main breakdown product of DDT in the environment and in the body); oxychlordane and trans-nonachlor, which are products of chlordane, a once-common termite treatment; and two pesticides, -hexachlorocyclohexane (-HCH), and hexachlorobenzene (HCB). PCBs are a group of chemical compounds found in coolants and lubricants in transformers, capacitors, other electrical equipment, and some consumer products. DDT was banned from commercial use in the United States in the 1970s, and PCBs are no longer permitted in new equipment; however, these highly persistent compounds are still widely found throughout the environment and in animals and people. Detectable levels of the organochlorine pesticides and PCBs were found in all women studied.
The researchers found that cases and controls had comparable levels of total organochlorine pesticides and total PCBs in their adipose tissue, after adjusting for age and body mass. There was no association between breast cancer risk and levels of total pesticides or total PCBs.
The researchers found an apparent association with increased risk for breast cancer only with the PCB congener 183, which accounts for about 9% of total PCBs. Little is known about this compound's toxicity, except that it weakly induces enzymes which may activate some carcinogens. However, no association was found between risk for breast cancer and the most abundant PCB congener, 153, which is a much stronger inducer and which has also been found to have estrogenic properties. The meaning of the finding for congener 183 is unclear, and the observation needs to be confirmed in other studies now in progress. The research team did not confirm a previously reported association with PCB congener 188.
The researchers continue to follow this study population and have conducted medical follow-ups of the cases to determine whether survival or recurrence of breast cancer may be related to body burden of organochlorines. A questionnaire was mailed to cases in order to obtain data on lifestyle changes and other patient characteristics that may have changed since the women were diagnosed with breast cancer. The women also provided new blood samples to permit study of changes in levels of organochlorine compounds over time.
The research is part of the Long Island Breast Cancer Study Project (LIBCSP), which is a group of studies that are being conducted to investigate environmental contaminants that may be responsible for the elevated rates of breast cancer in Nassau and Suffolk counties (Long Island), Schoharie County, NY, and Tolland County, CT. The LIBCSP is coordinated and funded by the National Cancer Institute (NCI) and National Institute of Environmental Health Sciences (NIEHS).
Beginning in the mid-1970s, findings from human studies began to emerge that suggested that organochlorine compounds or related compounds and PCBs may be associated with increased risk for breast cancer, the researchers explained. More recent studies, however, have not found an association, or only a small suggestion of a possible association, between exposure to the compounds and increased risk for breast cancer. A limitation of studies conducted today though, including the current study, the researchers said, is that a single measurement of body burden of these compounds made at the time of diagnosis may not reflect the cumulative lifetime exposure of individuals or age at exposure, particularly women who may once have had elevated levels of organochlorine compounds which were subsequently eliminated from their bodies. More sophisticated research designs are required which gather comprehensive environmental exposure histories.
The International Agency for Research on Cancer (IARC), which reviews and synthesizes evidence on carcinogenicity of toxic substances and exposures, rates DDT and PCBs as "possible" or "probable" carcinogens, based upon evidence from animal and human studies. Furthermore, some of the organochlorine compounds have been hypothesized to be endocrine disruptors - external agents that interfere with the role of natural hormones in the body, which suggests breast cancer as a potential disease outcome.
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* The study is titled " Breast Cancer Risk in Relation to Adipose Concentrations of Organochlorine Pesticides and Polychlorinated Biphenyls in Long Island, New York." Cancer Epidemiology, Biomarkers & Prevention is published by the American Association for Cancer Research.
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Schoharie County Component
In the Schoharie County component of the study, 36 women who were diagnosed with invasive or in situ breast cancer between 1995 and 1997, and 56 women who had benign breast disease or other non-breast cancer conditions participated. Blood serum and adipose (fatty) tissue were obtained. This population is too small to permit valid analysis.
Measurement of Body Burden of Organochlorine Compounds
In 1998, Dr. Stellman and colleagues published results of a systematic study of correlations between adipose tissue and serum levels of organochlorine compounds. The analysis validated that either tissue or blood can be used to assess a woman's body burden of organochlorine compounds, a point that has sometimes been challenged. Further, the researchers say, they demonstrated that the "profile" of individual organochlorine compounds found in human tissue was similar to that found in animals, such as fish and birds trapped in wildlife, suggesting similar environmental sources of exposure.