Breast Cancer and the Environment A Life Course Approach (2012) / Chapter Skim
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2 Background, Definitions, Concepts
2 Background, Definitions, Concepts
Pages 37-72
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Described here are the basics of the anatomy of the breast and breast development, types of breast cancer, and levels and trends in the incidence of the disease, focusing primarily on experience in the United States. The mechanisms that appear to result in female breast cancers and the pathways 37
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Approximately 92 percent of male breast cancers are estrogen receptor positive, compared with approximately 78 percent of breast cancers in women (Anderson et al., 2010)
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For example, breast tumors may be classified by tumor size, extent of spread beyond the tumor site (localized, regional, distant) , the anatomical characteristics of the tumor cells (e.g., ductal or lobular histology)
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. Triple Negative Breast Cancer Tumors lacking not only ER and PR expression but also HER2 are called triple negative breast cancers (TNBCs)
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and are African American. These cancers in African American women tend to be more advanced and of higher grade at the time of diagnosis than tumors in other racial groups (Carey et al., 2006; Stead et al., 2009; Trivers et al., 2009)
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. Breast Cancers in Women Without a Strong Family History Most women diagnosed with breast cancer do not have a strong family history of the disease and do not carry mutations in highly penetrant cancer-susceptibility genes.
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that have not been tested with the technologies available to date. Even so, statistical modeling suggests that low-penetrance gene variants may do at least as well in predicting risk as using traditional risk factors such as age at first birth, family history of breast cancer, and history of breast biopsy(ies)
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. Annual reports present data and analysis on cancer incidence, mortality, survival, and trends since 1975.
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Among older women, rates of invasive cancer rose during the 1980s and showed a slower increase during the 1990s. During the 1980s, use of menopausal hormone therapy had increased (Hersh et al., 2004; Glass et al., 2007)
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As reflected in Figure 2-2, a recent analysis found that for 2003–2007 incidence rates of invasive cancer did not significantly change, although use of HT continued to decline (DeSantis et al., 2011)
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For 2004–2008, the overall incidence of breast cancer was 136 cases per 100,000 among non-Hispanic white women, 120 per 100,000 among African American women, 94 per 100,000 among Asian and Pacific Islander women, and 78 per 100,000 among Hispanic women (who can be of any race)
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data from the National Cancer Institute show that the 5-year survival rate for women diagnosed with breast cancer during the period 2001–2007 was 77 percent among African American women and 91 percent among white women (NCI, 2011)
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Other factors contributing to poorer survival rates for African American women may include less access to early detection and treatment services as well as differences in tumor characteristics. Among Hispanic women, the incidence of breast cancer is consistently lower than for non-Hispanic white women or African American women, with greater differences at older ages (NCI, 2006; Hines et al., 2010; Liu et al., 2011)
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. An analysis of SEER data for California found that African American women had a 1.98 percent lifetime risk of developing triple negative breast cancer, whereas Hispanic women had a 1.04 percent lifetime risk and white women had a 1.25 percent risk (Kurian et al., 2010)
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. The risk for ER–/PR– and triple negative breast cancers is greater for African American women than for non-Hispanic white women, and reproductive factors have a more limited influence on risk for these forms of breast cancer.
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For example, the physical environment encompasses medical interventions, dietary exposures to nutrients, energy and toxicants, ionizing radiation, and chemicals from industrial and agricultural processes and from consumer products. These in turn are influenced by the social environment, because cultural and economic factors influence diet at various stages of life, reproductive choices, energy balance, adult weight gain, body fatness, voluntary and involuntary physical activity, medical care, exposure to tobacco smoke and alcohol, and Society Physical Environment Psychological Individual/Behaviors Cells/Tissue Metabolism Gene FIGURE 2-4 Multiple levels on which environmental exposures may act to influence breast cancer.
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A full appreciation of environmental influences on breast cancer calls for an analysis at multiple levels (Anderson and May, 1995) , from genetic and cellular mechanisms to the influence of societal factors.
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, the focus of this report was on the more proximate environmental exposures that may increase the risk of breast cancer. As understanding of the epidemiology, toxicology, and mechanisms of breast cancer continues to improve, efforts to develop effective interventions to mitigate risk may be aided by approaches that include modification of the social determinants of exposure to various risk factors.
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Such tools will also allow a deeper understanding of the cell signaling events that are disrupted in the process of breast carcinogenesis, providing a rational basis from which to identify potential environmental influences on breast cancer risk. For example, they can aid in studying the potential role of melatonin and circadian disruption as a modulator of breast cancer risk (Blask et al., 2011)
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will have consequences for particular tissues and that this provides a basis for anticipation of site concordance between rodents and humans in certain cases. Rodent models are also widely used by research scientists to investigate mammary carcinogenesis and the effects of timing and combinations of exposure to environmental factors.
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Assessing the Process of Carcinogenesis and Susceptibility to Environmental Exposures In addition to the use of experimental animals for standardized carcinogen bioassays, several animal models of chemically induced breast cancer have been used to evaluate (1) the cellular and molecular development and progression of breast cancer, and (2)
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Similar to human breast cancers, these chemically induced mammary carcinomas have altered expression of proteins that regulate cell growth and differentiation (e.g., HER2) , and most rat mammary tumors express estrogen and progesterone receptors.
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Collection of information on exposures that vary over time is difficult and often not carried out with sufficient detail. Cohort studies avoid the problem of recall bias, but they can be subject to other forms of bias.
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Extended follow-up of a study population can be expensive and administratively challenging. A listing of approximately 50 cohorts in the United States and other countries that have investigated breast cancer risks has been compiled by the Silent Spring Institute (2011)
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In cohort and case–control studies, exposure status can sometimes be objectively determined (e.g., by measuring weight) , but it often depends on reports by study participants of past or present experience (e.g., exposure to tobacco smoke in childhood or use of specific products in the home)
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Also, differences among individuals in their genetics or exposure to other risk factors can result in differing responses to equal doses of a substance. SOME MEASURES OF DISEASE RISK Estimates of disease risk associated with a factor of interest -- such as a personal characteristic (e.g., age)
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; and a ratio that is statistically significantly greater than 1.0 means that the exposure is associated with the disease, indicating that it is potentially a risk factor for the disease. Relative risk estimates and odds ratios represent an estimate of the strength of the association of a risk factor with breast cancer, but by themselves they do not provide insight into the underlying incidence of the disease and the absolute impact of a given factor.
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J Natl Cancer Inst Monogr 2010(41)
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2010. Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.
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2002. Rapidly rising breast cancer incidence rates among Asian-American women.
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2010. Comparative analysis of breast cancer risk factors among Hispanic and non-Hispanic white women.
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2010. Male breast cancer: Risk factors, diagnosis, and management (review)
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2007. Cancer incidence, mortality, and associated risk factors among Asian Americans of Chinese, Filipino, Vietnamese, Korean, and Japanese ethnicities.
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2010. Risk factors for ductal, lobular, and mixed ductal-lobular breast cancer in a screening population.
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2011. Silent Spring Institute guide to cohort studies for environmental breast cancer research.
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2011. Associations of breast cancer risk factors with tumor subtypes: A pooled analysis from the Breast Cancer Association Consortium studies.
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