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Vol. 03 Issue 1, Winter 1998

Research Commentary: Human Studies on DDT/DDE and Breast Cancer Risk
The Ribbon 

Terminology Key

ng/g = nanograms of the chemical per gram sampled tissue (blood, blood fat, fat, etc.)

  • a nanogram is one billionth of a gram
  • ng/g is the same as parts per billion (ppb)
  • one ng/g is equivalent to one ounce in about 7,490,000 gallons
ug/g = micrograms of the chemical per gram sampled tissue
  • a microgram is one millionth of a gram
  • mg/g is the same as parts per million (ppm)

OR = Odds Ratio (see Table 1)
RR = Relative Risk (see Table 1)

  

During the last six months, four new case-control studies have been published on body levels of DDT or DDE and breast cancer risk. These studies were conducted in Mexico City (López-Carrillo et al., 1997), Europe (van't Veer et al., 1997), New England (Hunter et al., 1997), and western New York State (Moysich et al., 1998). The major conclusions of all four studies were that high levels of DDE in the bodies of women did not appear to increase the risk of breast cancer, and in some of these studies, an inverse relationship was shown. This update provides brief descriptions of these studies, an overview of their strengths and limitations, and introduces some research questions that still need to be addressed.

DDT serum levels and breast cancer risk: A case control study from Mexico. The study by Lopez, et al. examined breast cancer risk in 141 pre- and post-menopausal women with breast cancer (cases) and 141 hospitalized women without breast cancer or other cancers (controls). The average level of DDE, a major break down product of DDT, in the blood (serum) of women with breast cancer was 562.5 ng/g compared to 505.5 ng/g in the hospitalized women without breast cancer. These differences were not statistically different. Even when the women with the highest levels of DDE were compared with those with the lowest levels of DDE, there was no increased risk of breast cancer (OR=0.97). Strengths of this study include that it was conducted in a country that still uses the insecticide DDT for malaria control, and that the women in the study resided in Mexico City for at least twenty years. Further, the researchers controlled for confounding factors that can affect breast cancer risk, including body size, duration of lactation, parity (number of births), menopausal status, and family history of breast cancer. Limitations included the use of hospital-based controls; if DDE levels were influenced by injuries or disease states, this could have affected the results of the study.

DDT and post-menopausal breast cancer in Europe: A case-control study. Van't Veer, et al. did not find a significant difference in the average level of DDE in a fat sample from the buttock area in 265 European postmenopausal women with breast cancer (1.35 mg/g) compared to hospitalized women without breast cancer (1.51 mg/g). In the Netherlands and Northern Ireland, the average levels of DDE were virtually identical in women with and without breast cancer, while in Germany, Switzerland and Spain, levels of DDE were higher in women without breast cancer compared to women with breast cancer. The fat samples from women with breast cancer were obtained seven days after hospital admission, but the published study results contained no information on whether the samples were obtained before or after surgery or chemotherapy. The study did control for many confounding factors, including parity, use of hormone replacement therapy, estrogen receptor status in women with breast cancer, time since menopause, history of breast cancer, history of benign breast disease, and current alcohol use. The study did not control for lactation history, which is important, since breast milk is a route of excretion for DDE.

Plasma organochlorine levels and the risk of breast cancer. The women in the prospective, nested case-control study by Hunter, et al. were drawn from the large cohort of women enrolled in the Nurses Health Study. The blood samples were obtained two to three years before the women developed breast cancer and they were matched with women from the same cohort that did not develop breast cancer. The average levels of DDE in the blood (plasma) of 236 women with breast cancer was 6.01 ppb compared to a slightly higher average level of 6.97 ppb in the 236 women without breast cancer. Further statistical analyses indicated that the women with the highest levels of DDE had a non-significantly lower risk of breast cancer (RR=0.72) as compared to the women with the lowest levels of DDE. High serum levels of PCBs (polychlorinated biphenyls) also were not associated with increased breast cancer risk. Strengths of this study included that it was prospective and controlled for many confounding factors, including history of breast cancer, history of benign disease, age at menarche, parity, age at birth of first child, duration of lactation and body size. The only positive statistical association of DDE with breast cancer risk factors identified in the control population in this study was that the women with the largest body mass tended to have higher levels of DDE in their blood.

Environmental organochlorine exposure and post-menopausal breast cancer risk. The study conducted on post-menopausal women from western New York State compared blood levels of DDE in 154 women with breast cancer with 192 women from the same community who did not have breast cancer. Levels of other organochlorines, including PCBs, Mirex and hexachlorobenzene (HCB) were also examined. One of the major strengths of this study was that it looked at the effect of lactation history on organochlorine levels and breast cancer risk. In the women that had lactated, the average levels of DDE in the blood (serum) were very similar in 85 women that had breast cancer (10.36 ng/g) compared with the 106 women without breast cancer (10.44 ng/g). In parous women that had never lactated, levels of DDE were higher in 46 women with breast cancer (13.16 ng/g) compared to the 61 non-lactating women without breast cancer (10.82 ng/g). But further statistical analysis indicated that risk was not significantly elevated in those women with the highest levels of DDE compared with those with the lowest levels of DDE who had never lactated (OR =1.83). This does point to the need to consider lactation history in studies evaluating the role of chemicals that persist and concentrate in breast fat, since breast feeding is a major route of excretion of these chemicals. What about other organochlorines? Researchers did find some evidence of increased risk of breast cancer in women with elevated blood levels of Mirex or PCBs, but only in parous women who had never lactated.

What are some of the major questions that have not yet been answered? One major question concerns differences in exposures to different forms and breakdown products of DDT. Not all forms of DDT and DDE are estrogenic, therefore, not all exposures would be expected to result in increased breast cancer risk. Some components of sprayed DDT were estrogenic, especially the form called o,p'-DDT. But, the most prevalent form of DDT currently in the environment, and present in food residues such as contaminated fish, is the non-estrogenic break down product called p,p'-DDE. Unfortunately, blood levels of DDE, as measured in these epidemiological studies, do not reveal what form of DDT a person may have been exposed to in the past. Therefore, a population could have high levels of DDE in their blood, but their exposure may have been to the non-estrogenic form of DDE. Studies of populations known to have been exposed to the sprayed estrogenic form of DDT are lacking. One population that has not been followed are native and American families that resided near the Panama Canal, an area sprayed daily with DDT for many years to control for malaria. Other research questions that need to be explored more fully include the role of early, in utero exposures to DDT and breast cancer risk, and if other factors, like diet and exercise, may play a role in modifying effects of estrogenic organochlorines.

Prepared by Suzanne M. Snedeker, BCERF Research Project Leader


References

Hunter, D. J., et al. (1997). Plasma organochlorine levels and the risk of breast cancer. New England Journal of Medicine 337, 1253-1258.

López-Carrillo, L., et al. (1997). Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico. Cancer Research 57, 3728-3732.

Moysich, K. B., et al. (1998). Environmental organochlorine exposure and postmenopausal breast cancer risk. Cancer Epidemiol. Biomarkers Prev. in press. Thanks to Dr. Moysich for providing the manuscript for review.

van't Veer, P., et al. (1997). DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study. British Medical Journal 315, 81-85.

For more information:
See Snedeker, S.M. (1996) DDT, DDE and Breast Cancer Risk, Fact Sheet #2, Cornell University, BCERF.

The BCERF web site has additional information on DDT/DDE and other chemicals and environmental risk factors.

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Last Update 07.05.05