Environmental pollutants and breast cancer

Environmental Health Perspectives, June 15, 2003 by Julia Green Brody, Ruthann A. Rudel

Breast cancer is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age. Rising incidence, increased risk among migrants to higher risk regions, and poor prediction of individual risk have prompted a search for additional modifiable factors. Risk factors for breast cancer include reproductive characteristics associated with estrogen and other hormones, pharmaceutical hormones, and activities such as alcohol use and lack of exercise that affect hormone levels. As a result, investigation of hormonally active compounds in commercial products and pollution is a priority. Compounds that cause mammary tumors in animals are additional priorities. Animal models provide insight into possible mechanisms for effects of environmental pollutants on breast cancer and identify chemical exposures to target in epidemiologic studies. Although few epidemiologic studies have been conducted for chemical exposures, occupational studies show associations between breast cancer and exposure to certain organic solvents and polycyclic aromatic hydrocarbons (PAHs). Population-based studies have been limited to a few organochlorine compounds and PAHs and have been mostly negative. A variety of challenges in studies of breast cancer and the environment may have contributed to negative findings. Lack of exposure assessment tools and few hypothesis-generating toxicologic studies limit the scope of epidemiologic studies. Issues of timing with respect to latency and periods of breast vulnerability, and individual differences in susceptibility pose other challenges. Substantial work is needed in exposure assessment, toxicology, and susceptibility before we can expect a pay-off from large epidemiologic studies of breast cancer and environment. Key words: benzene, breast cancer, carcinogens, endocrine-disrupting compounds, estrogen, hormonally active agents, organic solvents, PAHs, pesticides. Environ Health Perspect 111:1007-1019 (2003). doi:10.1289/ehp.6310 available via http://dx.doi.org/[Online 19 May 2003]

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Breast cancer is the most common cancer in women (Parkin et al. 2001). Incidence is highest in North America, Northern Europe, and Australia, where age-adjusted rates are 75-92 per 100,000 women (standardized to year 2000 world population), and lowest in Asia and Africa, where incidence is less than 22 per 100,000 (Parkin et al. 2001). Mortality has increased steadily from the 1960s until the late 1980s, when rates declined in many countries, including the United States (Parkin et al. 2001). Mortality continued to climb, however, for African Americans, whose mortality rates have exceeded the U.S. average since the 1980s (SEER 2002). Worldwide, breast cancer incidence continues to rise in all age groups, with an increase in U.S. age-adjusted incidence of more than 40% from the early 1970s to the late 1990s (Clegg et al. 2002; SEER 2002). An estimated 203,500 new invasive breast cancer diagnoses are expected in the United States this year, 54,300 in situ cases, and 45,000 deaths (ACS 2002). About 40% of new invasive cases are diagnosed in women younger than 60 years of age (ACS 1996), and breast cancer is the leading cause of cancer death among women 35-54 years of age (National Center for Health Statistics 1997).

The threat to women in mid life coupled with observations of substantial temporal and geographic variation and poor prediction of individual risk has prompted a search for modifiable risk factors. Because breast cancer risk changes over time and varies across geographic locations, factors associated with these variations may provide clues that can lead to prevention. Thus far, many correlates of risk have been identified, including a constellation of hormone-related reproductive factors. These factors account for a substantial portion of the variation in incidence, while also providing evidence that additional factors, probably modest in magnitude, remain to be discovered.

Taken together, epidemiologic studies of hormonal factors in breast cancer and animal studies of the hormonal activity and carcinogenic potential of certain synthetic chemicals suggest environmental pollutants as possible sources of risk. Compounds identified in laboratory studies as mammary carcinogens or hormonally active are in common commercial products and are ubiquitous pollutants to which women in industrial societies are widely exposed, so identifying effects on breast cancer has the potential for substantial public health impact, even if the relative risk associated with exposure is low.

In this article we identify promising leads in the study of environmental pollutants and breast cancer and the challenges in pursuing them. As background, we provide an overview of incidence trends and well-established and suggested breast cancer risk factors that inform environmental research. We review animal studies of chemicals that may be breast carcinogens, promote growth of breast cells and hormonally sensitive tumors, or affect mammary gland development and susceptibility. We assess current knowledge from the few epidemiologic studies of environmental pollutants, discuss the barriers to further progress, and identify research needs.