Influence of Localized DDT Exposure on Breast Cancer

Vicki L. Davis, Ph.D.
Center for Women’s Health, Cedars-Sinai Medical Center

The increase in prevalence of breast cancer over the past 50 years has been speculated to be related to the production and use of many chemicals and pesticides, such as DDT, that have now been shown to have hormonal activities. That is, DDT and other chemicals can mimic or interfere with natural hormonal responses in humans and animals. Therefore, the exposure to these unnatural hormones may disrupt normal responses resulting in accelerated breast cancer development. Some studies in women have suggested that higher levels of the pesticide DDT stored in breast fat increased breast cancer risk, while other studies show no increase in risk, indicating that more evidence is needed to evaluate the role of DDT in breast cancer. DDT has been banned in the US for about 20 years; however, this pesticide is persistent and remains in the environment and stored in the fat of humans and animals. In addition, DDT remains in use in third world countries; therefore, it continues to invade our environment despite the ban in this country. Every person will carry some level of DDT within their body for their lifetime.

In the body and the environment, DDT is broken down into related compounds that have been shown to either act like estrogens or anti-androgen (inhibit the actions of the male sex hormones, androgens). The ability of the DDT compounds to mimic the female sex hormones as well an inhibit the action of the male sex hormones has had devastating consequences on sexual development of wildlife exposed to DDT by environmental contamination. It is reasonable to speculate that the hormonal actions of DDT may be linked to breast cancer, since growth of the cancer-prone cells in the breast is stimulated by estrogens and inhibited by androgens. Because DDT is not eliminated from our bodies after exposure, remains stored in the fat surrounding the breast tissue where cancer originates, and can act like hormonal agents, DDT has tremendous potential to influence breast cancer. Therefore, we will investigate how localized exposure of these chemicals influence hormonally regulated responses such as growth and tumor development in the mammary glands of mice.

We will use a line of mice that develops mammary cancer that frequently progresses to metastatic cancer in the lungs. The cancer in the mice is induced by the most common gene found to be increased in human breast cancer (the oncogene, neu, or HER2). We will locally treat the mammary gland with DDT and assess the effects of DDT on tumor outcomes, such as incidence, age of onset, and progression of the disease to invade the lungs. From these data we will be able to demonstrate that the individual DDT compounds can act like an estrogen or an anti-androgen to influence breast tissue to develop cancer.

By determining whether DDT can directly influence growth and tumor development in the breast by mimicking the natural hormones, we can help assess risk in women and devise means to counteract the actions of this chemical prior to tumor onset.

Progress Report, Year 1 (2001)

DDT can mimic or interfere with natural hormonal responses in humans and animals; therefore, exposure to these man-made hormone imitators may disrupt normal responses resulting in earlier breast cancer development. In the body and the environment, DDT is broken down into related compounds that have been shown to either act like an estrogen or anti-androgen (inhibits the actions of the male sex hormones, androgens). Because DDT is not eliminated from our bodies after exposure, but remains stored in the fat surrounding the breast tissue, and it acts like other hormones, DDT has tremendous potential to influence breast cancer. In this study, our goals are to determine if localized exposure to DDT influences breast cancer development and if its effects are related to the hormonal activities of this environmental contaminant. We are examining how the individual DDT chemicals influence the development of tumors in the mammary glands of mice induced by the most common gene found to be increased in human breast cancer (the oncogene, neu, or HER2).

All the female mice for the tumor study have begun treatments. The treatments include two DDT compounds, one with estrogen-like activity and the other with anti-androgen activity. These are being compared to groups treated with a known estrogen (one naturally produced in women) and anti-androgen (one used to treat prostate cancer). Treatments are designed to only affect the mammary gland and not the entire body to determine if DDT in breast fat influences cancer formation. The onset of tumor development, growth of the tumors, and number of females that develop mammary cancer from each treatment group are currently being assessed. The first groups of females treated have just begun to develop tumors. It is too early to predict how these chemicals influence mammary cancer development, but results will be continually evaluated as these mice age.

From the data generated in these mice, we will be able to demonstrate whether the individual DDT compounds can act like an estrogen or an anti-androgen to influence breast tissue to develop cancer. By determining that DDT can directly influence growth and tumor development in the breast by mimicking the natural hormones, we can help assess risk in women and devise means to counteract the actions of this chemical prior to tumor onset.

Progress Report, Year 2 (2002)

DDT can mimic or interfere with natural hormonal responses in humans and animals; therefore, exposure to these man-made hormone imitators may disrupt normal responses resulting in earlier breast cancer development. In the body and the environment, DDT is broken down into related compounds that have been shown to either act like an estrogen or anti-androgen (inhibits the actions of the male sex hormones). Because DDT is not eliminated from our bodies after exposure, but remains stored in the fat surrounding the breast tissue, and it acts like other hormones, DDT has tremendous potential to influence breast cancer. In this study, our goals are to determine if the DDT chemicals stored in the breast can influence breast cancer development and if its effects are related to the hormonal activities of this environmental contaminant. The concern about exposure to DDT and breast cancer risk has generally been assigned to the weak estrogen-like activities of some DDT compounds. However, the most abundant DDT chemical has not been considered despite its strong anti-androgen activity. We were concerned that this prevalent and potent DDT compound should be tested for its potential to influence the development of breast tumors. In this study, two individual DDT chemicals with the different hormone activities (estrogenic and anti-androgenic) are examined for their influence on cancer development using a mouse model that develops mammary cancer caused by the most common cancer causing gene in human breast cancer (the oncogene, neu, erbB2, or HER2).

All the female mice have now been treated. The study is still ongoing, but most of the female mice have reached maximum age allowing us to see how these treatments are acting in the mammary glands. The treatments include two DDT compounds, one with estrogen-like activity (o,p DDE) and the other with anti-androgen activity (p,p DDE). These are being compared to groups treated with a known estrogen (one naturally produced in women) and anti-androgen (one used to treat prostate cancer). Treatments are designed to only affect the mammary gland and not the entire body to determine if DDT found in breast fat influences cancer formation. The age when tumors are first detected, the number of females that develop mammary cancer, and the number of females with tumors that have spread to the lungs from each treatment group are currently being assessed. Most of the females treated have already developed tumors, although some are still aging. We found that the anti-androgenic DDT chemical was the most active at causing the mammary tumors to begin at younger ages. The estrogenic DDT chemical also accelerated tumor development, but to a lesser extent than the anti-androgenic compound. The results with one potential ratio of p,p DDE to o,p DDE that may occur in nature suggests that the ratio these two compounds of may be important to how DDT influences cancer risk. Therefore, our studies with the two compounds indicate that the DDT stored locally in the breast has the potential to accelerate the development of tumors. These results may help us understand how DDT acts in the breast, why studies in women report conflicting risks on breast cancer. The effects of DDT on tumor invasion are still being investigated, but these results should help us determine if DDT can influence tumor aggressiveness and patient survival.