Organochlorines in the environment and breast cancerBMJ 1994; 308 doi: https://doi.org/10.1136/bmj.308.6943.1520 (Published 11 June 1994) Cite this as: BMJ 1994;308:1520
- T Key,
- G Reeves
Women have been worried recently by press accounts of six comparatively small epidemiological studies suggesting that certain organochlorines in the environment might increase the risk of breast cancer.*RF 1-6* The studies were concerned with 1, 1-dichloro-2, 2-bis(p-chlorophenyl) ethylene (DDE), the main metabolite of the insecticide DDT and also with the polychlorinated biphenyls (PCBs), a group of compounds used in industry - for example, as electrical insulators. How strong are the grounds for concern?
The results are summarised in the figure. The individual estimates plotted are ratios of the mean concentrations of DDE or of polychlorinated biphenyls in fat or serum in women with breast cancer divided by the mean concentrations in control women without breast cancer. Summary ratios were derived from the weighted averages of the log ratios. For DDE the summary ratio was 1.11 (99% confidence interval 0.97 to 1.26). In other words, the women with breast cancer had slightly higher concentrations of DDE than controls but the difference was not statistically significant. For the polychlorinated biphenyls the summary ratio was 1.01 (0.92 to 1.10) - indistinguishable from no difference at all.
When they were first published two of the studies - by Falck and colleagues3 and by Wolff and colleagues4 - created considerable anxiety with respect to DDE, but they were based on only 20 and 58 women with breast cancer respectively. The recent study of Krieger and colleagues6 had as many cases as all the previous studies put together and used serum collected an average of 14 years before diagnosis, whereas the other studies used fat or serum collected shortly before or after diagnosis. Krieger and colleagues found no association of DDE with breast cancer.
Widespread use of DDT began in the United States in 1946 and increased until 1959. It then declined steadily until it effectively stopped in 1972.7 DDT accumulates in the body, but the reduction in its use caused concentrations in adipose tissue in the general population to fall from about 8 ppm in 1970 to about 2 ppm by 1983.7 Polychlorinated biphenyls were first produced commercially in 1929 and since then have been used in many industrial products. They were detected as environmental contaminants in 1966, and in the United States production ceased in 1977. In 1972, 61% of the American population was estimated to have concentrations of polychlorinated biphenyl in adipose tissue above 1 ppm, but this had dropped to 6% by 1983.7 In most developed countries patterns of use of both types of organochlorines have resembled those in the United States, but DDT is still widely used in some countries to control mosquitoes.
Temporal trends in breast cancer rates are difficult to relate to changes in exposure to suspected risk factors because the rates are affected by complex variations in the known risk factors for breast cancer such as age at menarche, age at first birth, parity, and age at menopause. In several developed countries, however, breast cancer mortality rates were high before any widespread exposure to DDT or polychlorinated biphenyls, and the rates have not risen strikingly since these chemicals were introduced.
The International Agency for Research on Cancer has classified DDT as “possibly carcinogenic” to humans, largely because it can cause liver cancer in experiments on animals.8 Another reason for suggesting that DDT from the environment might cause breast cancer is that DDT is oestrogenic. This is a very theoretical risk; even in large doses DDT is only weakly oestrogenic in animals, and it has not been shown to have oestrogenic effects in women. Oestrogen replacement therapy, which has clear oestrogenic effects, may increase the risk of breast cancer by about 30% after 15 years of use,9 so any small oestrogenic effect of DDT in the environment would probably be impossible to detect by epidemiological studies.
Polychlorinated biphenyls have been classified by the International Agency for Research on Cancer as “probably carcinogenic” to humans, with a possible association with cancers of the liver and biliary passages.10 Polychlorinated biphenyls are sometimes referred to as oestrogenic, but in fact some show antioestrogenic activity, and no oestrogenic effects of polychlorinated biphenyls have been established in women.11,12 There is, therefore, no strong reason to expect polychlorinated biphenyls to cause breast cancer rather than any other cancer.
Putting all this evidence together, we conclude that it is unlikely that DDT in the environment increases the risk of breast cancer. However, all published epidemiological evidence comes from the six studies cited - based on only 301 women with breast cancer and 412 women without. The question is so important that it seems justified to examine it further in at least the same number of women again, using specimens collected before the women develop breast cancer. For polychlorinated biphenyls there is no evidence for an association with breast cancer risk, and there seems to be no need to pursue this question further.