The origins of breast cancer are complex. Many different pathways incorporating individual, societal, and cultural variables lead to this disease. Risk factors for pre- and post-menopausal breast cancers differ. The biology of breast cancers varies, often dramatically. But our understanding of this complexity is rapidly growing thanks to laboratory and epidemiologic research. We’ve learned that critical events affecting breast cancer risk begin early — during fetal development and continuing through puberty, adolescence, and adulthood. Throughout life, the timing, duration, and combinations of environmental exposures, along with age at first menstruation, timing and number of pregnancies, and activity levels, body size, among other variables, influence breast cancer risk—but not in the same ways for all kinds of breast cancer. In many respects this collection of interacting biologic, behavioral, environmental, and societal variables resembles a complex ecosystem, woven together over time, creating system conditions that sustain health or give rise to disease.
The good news is that this growing understanding supports new opportunities for breast cancer prevention, although the complexity makes clear that, to be successful, we will need to act with less than perfect information. Demonstrating a causal relationship between critical events during fetal development or puberty and breast cancer in adulthood is far easier in laboratory animals than humans. For example, increased breast cancer risk in women after they were exposed to diethylstilbestrol (DES) in utero has only recently become more solidly established — decades after its use during pregnancy was thankfully terminated for other reasons. This illustrates a core public policy dilemma. If we decide to wait for proof of a causal relationship in humans before addressing a risk factor for a complex disease like breast cancer, we will miss opportunities to prevent additional suffering. At the same time, we also need to consider the consequences of mitigating exposures that turn out not to be causally linked to the disease. It comes down to these questions: What is the weight of evidence? Who bears the burden of proof? When do we know enough to act? What kind of mistakes are we willing to make? What are the consequences and to whom? What are the alternatives? Who should decide?
Radiation raises the risk of breast cancer, particularly when exposures occur at a younger age. Alcohol use, smoking, and some pharmaceuticals also add to the risk. But the role of most environmental chemicals and contaminants is uncertain and poorly studied, particularly as they interact with other established risk factors mentioned above.
Several chemicals have been causally linked to breast cancer in women, including ethylene oxide, benzene, and 1, 3-butadiene. Plausible, although somewhat less extensive evidence, adds polychlorinated biphenyls, some polycyclic aromatic hydrocarbons, and additional solvents to the list. But the effects of most environmental chemicals have never been studied in women who are exposed occupationally, from consumer products, or general environmental contamination. Instead, much of the limited amount that we do know comes from laboratory animal studies.
Animal studies are generally accepted as being predictive of responses in humans although there is some disagreement about the relevance of high-dose studies for people exposed at lower levels. In 2007 scientists from Silent Spring Institute, a research organization studying the environment and breast cancer, published in the journal Cancer the results of a literature search identifying 216 chemicals associated with increases in mammary gland tumors in at least one well-conducted animal study. Of these, 73 have been present in consumer products or as contaminants of food, 35 are air pollutants, 29 are produced at more than 1 million pounds per year in the United States, and 25 have involved occupational exposures to more than 5,000 women. Yet, despite the near certainty of widespread exposures to many of these chemicals, the findings have triggered virtually no regulatory or other policy response. Chemical or product manufacturers have not been required to examine the safety of their chemicals more closely, none of these chemicals has been removed from the marketplace because of breast cancer risk, and the overwhelming majority of chemicals identified as animal mammary carcinogens have never been included in an epidemiologic study of breast cancer. This urgently needs to change.
Laboratory and epidemiologic research, of course, must continue. Additional chemicals should be screened. Basic safety data are lacking for thousands of chemicals in commerce. Cancer assays should be modified to incorporate developmental exposures. The mammary gland should routinely be examined for structural alterations after developmental exposures. Epidemiologic studies need to be designed to account for early life exposures, although assessing past environmental exposures poses serious challenges.
But, this is not enough. Steps to reduce exposures to chemicals for which there is evidence of a link to breast cancer are urgently needed. Plausible evidence from animal or human studies should be sufficient to shift the burden of proof onto chemical or product manufacturers to demonstrate convincingly lack of harm from exposure. And if plausible evidence cannot be refuted in a reasonable period of time, suspect chemicals should be removed from commerce and replaced with safer alternatives. It is important to remember that even if the increased risk associated with a chemical exposure is relatively modest, the public health impact of reducing exposures would be profound when the exposed population is large.
For too long the complexity of breast cancer has kept us from taking steps to reduce or eliminate exposures to environmental chemicals plausibly woven into the causal web of this disease. Scientific uncertainty will always accompany our understanding of the origins of breast cancer and other complex diseases. This should not be an excuse to fail to act on the basis of what we know.