The Ribbon Newsletter

In my ten years with BCERF, I have written about chemicals and cancer risks in a variety of formats, from detailed critical evaluations of the literature for scientists, to fact sheets and work shops for consumers, professionals, and cancer advocates, to Research Commentaries published in The Ribbon. Occasionally, I find myself between the proverbial rock and a hard place because of the gaps (or rather crevasses) in scientific approaches that have not allowed us to go forward to fully determine what factors do or do not contribute to breast cancer risk. How can we better define how and to what extent environmental factors contribute to rising rates of breast cancer here in the United States, and in countries like the People's Republic of China and Japan, where rates have skyrocketed in the last 30 years? Unlike my usual pattern of critiquing one or several research studies, I ask your indulgence in using a different approach in this commentary. I would like to "unpack" several issues, specifically, how does socioeconomic status (SES) affect breast cancer survivorship and breast cancer rates? And, what do we know (and what do we need to know) about how SES (including "buying power" or lack thereof) affects choices related to risk, from what we eat, to how we behave, to where we live, to exposures to specific chemicals of concern?

The definition of Socioeconomic Status (SES) in "A Dictionary of Epidemiology" (Last, 2001) is:

Descriptive term for a person's position in society, which may be expressed on an ORDINAL SCALE using such criteria as income, education level attained, occupation, value of dwelling place, etc.

It is known that we have a paradox in breast cancer related to SES. Breast cancer mortality rates (dying of breast cancer) tend to be higher in those lowest on the income scale, yet breast cancer incidence (developing breast cancer) tends to be higher with a greater income. What are the factors that may explain these trends, which are seen worldwide, and how is SES a "proxy" factor for many other factors that affect breast cancer survivorship and risk?

SES and Surviving Breast Cancer

Switzerland has one of the highest life expectancies and average incomes in the world, with an extensive network of accessible medical treatment facilities. Yet, a study conducted by Bouchardy and colleagues (Bouchardy et al., 2006), found that social disparities affected the rates of dying from breast cancer in their study based in Geneva, Switzerland. Patients that had the lowest economic class had a 2.4-fold higher risk of dying from breast cancer compared to women of the highest economic class. Why is this so? The authors found that despite access to health care, women with a lower income tend to be screened less frequently, and when screened had a more advanced stage of breast cancer. After a diagnosis of breast cancer, women with a lower income tended to have less use of breast conserving surgery, hormone therapy, and chemotherapy. Yet, when all of these treatments were controlled for, the women with the lowest SES still had a 1.8-fold higher risk of dying of breast cancer compared to Swiss women of higher incomes. It is still not completely understood as to why, despite dramatic increases in life expectancy and improvements in living conditions, social disparities still contribute to a poorer outcome, and a higher death rate from breast cancer in women with low SES. Social inequality, the authors conclude, may be an independent factor affecting breast cancer survivorship.

Alternatively, could there be unidentified factors that contribute to a poorer outcome that are related to the environment of women with less economic buying power? Few studies have evaluated how economic status might affect the development of the disease because of, for example, differences in working conditions, exposure to pollution, dietary choices, or use of household chemicals and personal care products. The time may have come to stop speculating and to start thinking outside the usual box to determine how we can test hypotheses of how income affects the total environment and ultimate disease outcome. While there is increased awareness of how economic justice issues affect chemical exposures, we have only started to explore how economic factors affect breast cancer risk in socially disadvantaged populations.

Disparities have been noted in breast cancer death rates between white women compared to women of African American ethnicity in the United States: African American women have poorer survivorship even after controlling for SES (Newman et al., 2006). Why there are differences in survivorship remains a matter of speculation. Earlier studies suggested differences in screening frequency with subsequent diagnosis of a more advanced, frequently metastatic stage of the disease in African American women compared to white women (Heck and Wagener, 1997). However, other studies have shown when delivery of care is tightly controlled in a randomized trial (controlled for stage of disease, work-up, and delivery of care), the survivorship was still poorer in African American women compared to white American women (Albain et al. 2003 [ref. no. 25], as cited by Newman et al., 2006). While current hypotheses suggest possible genetic differences in the underlying morbidity risks in women of different ethnicities, as well as differences in when women bear their children, could there be other explanations? Could causal factors be different because of different diets (protective and non-protective elements) or exposures to different types and quantities of environmental chemicals encountered on the job, or in the local neighborhood, or different patterns of use of personal care products? We have no definitive answers, but these are questions and avenues that need in-depth exploration.

High Rates of Breast Cancer in the United States: Individual versus Community Effects

Within an urban community, researchers have found higher risk of advanced stage of breast cancer in women living in areas with lower levels of education and income regardless of ethnicity. Merkin and colleagues evaluated risk of advanced staged diagnosis of breast cancer in women living in New York City. After adjusting for age and year of diagnosis, low SES increased the chances of an advanced staged breast cancer diagnosis 50% in black women and 75% in white women (Merkin et al., 2002).

A very interesting study was conducted by Robert and colleagues from the University of Wisconsin and the Fred Hutchinson Center in Seattle, Washington (Robert et al., 2004). They asked the questions: are women at higher risk for breast cancer if they as individuals have a higher SES, or if they live in a community that has a higher SES overall, or if they live in an urban community? This case control study included 14,667 women residing in Wisconsin. These researchers looked at individual risk factors, including age, mammography use, family history, parity, age at first birth, alcohol intake, body mass index, hormone replacement use, oral contraceptive use, and menopausal status. After all of these individual risk factors were controlled for, they found that women living in communities with the highest SES had about a 20% higher risk of having breast cancer compared to women living in communities with the lowest SES. Risk of having breast cancer was also higher (about 17% higher) for women living in urban compared to rural communities. These authors stated that future research studies needed to determine why living in communities with higher SES or in urban communities results in a higher risk of breast cancer.

In California, there are wide geographical variations in breast cancer rates. A study on how SES (based on occupation, income, and education) and urbanization affected regional rates of invasive breast cancer was conducted by Reynolds and colleagues (Reynolds et al., 2005). The study was based on cases identified in the California Breast Cancer Registry between 1988-1997. In this study, researchers found that regional variations in ductal breast cancer rates were largely attributed to variations in SES and urbanization. However, for lobular breast cancer, in the San Francisco Bay area breast cancer risk was still moderately elevated even after controlling for age, race, urban/rural location, and SES. This is one of the few studies that considered the type of breast cancer and relationship to SES and urbanization.

How does income relate to chemical exposures? A review of environmental health studies suggests that lower SES is associated with higher exposures to certain environmental chemicals, including a higher likelihood of living closer to hazardous waste sites (such as hazardous waste facilities in Detroit, and the uranium mines near native American reservations in the western United States); indoor air pollutants (use of tobacco products; fuel exhaust; unvented gas heaters); and poorer water quality (Evans and Kantrowitz, 2002). However, these are generalizations, and do not fully take into consideration a basic toxicology principle; effects are determined by the hazard of that particular chemical, and the extent and timing of exposure. What we lack for breast cancer epidemiology is an index of how exposures to specific chemicals of concern differ (or not) according to income, including the extent of exposure to known mammary carcinogens and endocrine disrupting chemicals. Does income level affect, for example: what is chosen for cleaning products; the carpets and furniture in homes treated with endocrine disrupting chemicals; the use of building materials that may out-gas chemicals of concern; storage of paper (including books) that may off-gas known carcinogens such as formaldehyde; the presence of closed ventilation systems in higher income dwellings compared to open windows in lower income households; or prescription rates and use of over the counter as well as prescribed medications?

Researchers are starting to evaluate how use of personal care products and medications affects environmental exposures (Hauser et al., 2004; Liebig et al., 2006; Ruckart et al., 2004; Rudel et al., 2003; Schettler, 2006; Spaeth, 2000). Many of our regulations on air pollutants have emphasized limiting releases into air and water, but have not yet addressed the problem of identifying and controlling exposures encountered in homes. Polycyclic hydrocarbons and certain volatile organic chemicals (VOCs) have been identified as chemicals of health concern detected in indoor air (Spaeth, 2000; Guo et al., 2004). Researchers are starting to call attention to the need for interdisciplinary collaborations that study pollutants in relationship to specific socioeconomic indicators and health outcomes (Bell et al., 2005).

Some researchers have suggested a more rigorous reexamination of indoor air regulations and prevention measures (Spaeth, 2000). Some of the VOCs identified in indoor air include: 1,1-dichoroethene, chloroform, methylene chloride, trichlorethene, benzene, tetrachloroethane and styrene. The Silent Spring Institute has published the results of pilot studies on levels of environmental chemicals in the air and dust samples in households on Cape Cod (Rudel and Brody, 2001; Rudel et al., 2003). There are few human studies, and none of adequate size or quality, that have investigated exposures and breast cancer risk with residential exposures to these chemicals. There is suggestive evidence from occupational studies conducted in China and Sweden that exposure to benzene in occupational settings is associated with a higher breast cancer risk (Hansen, 1999; Petralia et al., 1998; Pollán and Gustavsson, 1999; Snedeker, 2006). Most studies on chemicals and cancer incidence have been conducted in occupational settings (Boffetta, 2004; Snedeker, 2006). It now may be time to turn our attention to the impact of residential exposures to chemicals as affected by income levels as well as cultural and community influences.

Ways to investigate social status and environmental hazards

There have been models published on ways to investigate how social status affects exposure to environmental hazards. Cutter and colleagues developed a "Social Vulnerability" index to environmental hazards in the United States (Cutter et al., 2003). This model has three components; conditions that make people or places more vulnerable to an "extreme" natural event (e.g. a disaster, chemical leak, etc.); assumption that vulnerability is a social condition; and that societal status may influence the ability to resist or bounce back from exposures to environmental hazards. In this model, the potential for an exposure to be hazardous (capacity to cause harm) is not only affected by the properties of the chemical, but also by geography (affects how physically close you are to the hazard), and social fabric (includes experience, perception of risk, and the actual built environment). So, there are both biological and social elements of vulnerability in this model. However, such models have not yet been used to specifically study how breast cancer risk is affected by the interaction between social status and exposure to environmental risk factors.

Dramatic Rising Rates of Breast Cancer in Urban China

In many ways, urban areas of the People's Republic of China are "living laboratories" allowing scientists to study how rapid urbanization and westernization affects many chronic diseases, from heart disease to many types of cancer. Breast cancer rates (incidence) have risen dramatically in urban areas of China during the last 30 years. Hong Kong has the highest breast cancer incidence rate in Asia. Studies examining trends in breast cancer rates from 1973-1999 showed rates increasing at the rate of 3.6% per year in Hong Kong, China (Leung et al., 2002) (age standardized rate). China has 20% of the world's population of women, so changes in breast cancer rates may have a major effect on global rates of breast cancer. The authors of this paper suggested that the move toward higher rates may be due to following a more western lifestyle. Breast cancer rates in Hong Kong women were 2 to 3 fold higher in women born in the 1960s compared to women born at the turn of the last century (1900). Breast cancer rates started to rise dramatically in women who were born after 1935. Because Hong Kong did not have an organized mammographic screening program until the mid-1990s, it is unlikely that the rise in breast cancer rates can be attributed solely to more widely available screening services, and rates have not been dramatically higher since the time when screening has been more common. The authors hypothesize that there may be a "set of exposures that exerts its primary effect early in life" (Leung et al., 2002, pg. 987).

Other factors that may have affected breast cancer risk include lower parity, not having children at all, rising rates of obesity, and a more sedentary lifestyle. While the age of menarche in China has decreased from an average of 12.60 years in 1981 to 12.07 in 2001, the extent to which this explains the rising rates reported in this paper is not clear. Breastfeeding rates have also changed in China, with it being common practice in 1900, while very low levels were recorded in the 1980s, and rates starting to rise again by the late 1990s.

Most of the cancer registries in China are located in large urban areas, and little information is available to assess national trends, including if similar rises in breast cancer rates are occurring in rural areas as western lifestyles are adopted. More recent estimates of breast cancer risk indicate that between 2000 and 2005 existing cancer registries in China showed a 27.5% increase in the risk of female breast cancer (Yang et al., 2005). But again, these rates are largely reflective of large urban areas. Studies have started to address the causes of the rising rates of breast cancer in urban areas of China. A recent study (Leung et al., 2005) suggested that about 45% of the risk of developing breast cancer in China can be attributed to increased longevity during the last 25 years, and 55% to a "secular rise" in breast cancer rates ("secular" defined as changes due to westernization and accompanying socioeconomic changes). While again, lowered fertility, younger age at menarche, older age at childbirth, obesity and inactivity have been suggested as risk factors that may contribute to rising rates of breast cancer in a westernized urban China, there were no studies located that had investigated exactly how westernization has affected specific dietary patterns, and whether there have been changes in personal habits, and use of products that may include chemical carcinogens or endocrine disrupting chemicals.

Changes in breast cancer rates with lifestyle changes are not only happening in Asia; a recent review of migration studies published in the Journal of the National Cancer Institute suggested that Polish immigrants to the United States have increased rates of breast cancer that may be due to dietary changes, specifically a decrease in cabbage consumption (Nelson, 2006). Cabbage is a cruciferous vegetable that contains glucosinolates that can form anti-carcinogens (isothiocyanates) in the body. Consumption of glucosinolate containing foods, and its affect on cancer risk, and gene-environmental interactions, is being studied in Shanghai, China (Fowke et al., 2003).

Unpacking the SES puzzle: Challenges and Future Directions

How can a plethora of factors rooted in social status and economics be adequately studied for how they individually, and collectively, affect breast cancer risk and survivorship? We may need to move toward the use of computer models that could take into account the large number of complex factors that may affect breast cancer risk, to determine how both a western lifestyle and elements of SES impact on breast cancer risk in different ethnic populations in different parts of the world. The modeling to look at the social and biological interface may need to use the developing field of bioinformatics. It is clear that our practice of looking at single factors or types of factors needs to evolve. Study objectives are frequently determined by the expertise of the investigators, resulting in studies that may primarily look at either dietary or chemical factors while controlling for established breast cancer risk factors. Resources frequently limit the scope of epidemiological studies. Funding to support characterizing the extent of chemical exposures in non-occupational settings is relatively recent, and this is still an emerging area of research.

Future efforts may need to focus on developing new paradigms and new methods to evaluate how society, cultural values and economics all impinge on choices and conditions that affect cancer risk, as well as how social justice and lower economic status affect risk because of adverse locations and lack of resources, including lack of access to health care. The time may have come for economists, epidemiologists, and cancer biologists to think outside the usual box to more fully understand how socioeconomic status may affect the risk of breast cancer and other chronic diseases.

Bell, M. L., O'Neill, M. S., Cifuentes, L. A., Brage, A. L. F., Green, C., Nweke, A., Rogat, J., and Sibold, K. (2005). Challenges and recommendations for the study of socioeconomic factors and air pollution health effects. Environmental Science and Policy 8, 525-533.

Boffetta, P. (2004). Epidemiology of environmental and occupational cancer. Oncogene 23, 6392-6403.

Bouchardy, C., Verkooijen, H. M., and Fioretta, G. (2006). Social class is an important and independent prognosis factor of breast cancer mortality. International Journal of Cancer 119, 1145-1151.

Cutter, S. L., Boruff, B. J., and Shirley, W. L. (2003). Social vulnerability to environmental hazards. Social Science Quarterly 84, 242-261.

Evans, G. W., and Kantrowitz, E. (2002). Socioeconomic status and health: the potential role of environmental risk exposure. Annual Review of Public Health 23, 303-331.

Fowke, J. H., Shu, X.-O., Dia, Q., Shintani, A., Conaway, C. C., Chung, F.-L., Cai, Q., Gao, Y.-T., and Zheng, W. (2003). Urinary isothiocyanate excretion, Brassica consumption, and gene polymorphisms amoung women living in Shanghai, China. Cancer Epidemiology Biomarkers and Prevention 12, 1536-1539.

Hansen, J. (1999). Breast cancer risk among relatively young women employed in solvent-using industries. American Journal of Industrial Medicine 36, 43-47.

Hauser, R., Duty, S. M., Godfrey-Bailey, L., and Calafat, A. M. (2004). Medications as a source of human exposure to phthalates. Environmental Health Perspectives 112, 751-753.

Heck, K. E., and Wagener, D. K. (1997). Socioeconomic status and breast cancer mortality, 1989 through 1993: an analysis of education data from death certificates. American Journal of Public Health 87, 1218-1222.

Last, J. M., ed. (2001). A Dictionary of Epidemiology, 4th ed. (New York, Oxford University Press).

Leung, G. M., Thach, T. Q., Chan, E., Foo, W., Meng, O., Fielding, R., Lam, W. W. T., Hedley, A. J., Wong, C.-M., and Lam, T.-H. (2005). Short-term, medium-term, long-term, and lifetime risks of developing and dying breast carcinoma in a westernized Chinese population. Cancer 103, 501-508.

Leung, G. M., Thach, T. Q., Lam, T.-H., Hedley, A. J., Foo, W., Fielding, R., Yip, P. S. F., Lau, E. M. C., and Wong, C.-M. (2002). Trends in breast cancer incidence in Hong Kong between 1973 and 1999: an age-period-cohort analysis. British Journal of Cancer 87, 982-988.

Liebig, M., Moltmann, J. F., and Knacker, T. (2006). Evaluation of measured and predicted environmental concentrations of selected human pharmaceuticals and personal care products. Environmental Science and Pollution Research International 13, 110-119.

Merkin, S. S., Stevenson, L., and Powe, N. (2002). Geographic socioeconomic status, race, and advanced-stage breast cancer in New York City. American Journal of Public Health 92, 64-70. Nelson, N. J. (2006). Migrant studies aid the search for factors linked to breast cancer risk. Journal of the National Cancer Institute 98, 436- 438.

Newman, L. A., Griffith, K. A., Jatoi, I., Simon, M. S., Crowe, J. P., and Colditz, G. A. (2006). Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status. Journal of Clinical Oncology 24, 1342-1349.

Petralia, S. A., Chow, W., McLaughlin, J., Jin, F., Gao, Y., and Dosemeci, M. (1998). Occupational risk factors for breast cancer among women in Shanghai. American Journal of Industrial Medicine 34, 477-483.

Pollán, M., and Gustavsson, P. (1999). High-risk occupations for breast cancer in the Swedish female working population. American Journal of Public Health 89, 875-881.

Reynolds, P., Hurley, S. E., Quach, A.-T., Rosen, H., Von Behren, J., Hertz, A., and Smith, D. (2005). Regional variations in breast cancer incidence among California women, 1988-1997. Cancer Causes and Control 16, 139-150.

Robert, S. A., Strombom, I., Trentham-Dietz, A., Hampton, J. M., McElroy, J. A., Newcomb, P. A., and Remington, P. L. (2004). Socioeconomic risk factors for breast cancer; distinguishing individual- and community-level effects. Epidemiology 15, 442-450.

Ruckart, P. Z., Orr, M. F., and Kaye, W. E. (2004). Hazardous-chemical releases in the home. Journal of Environmental Health 67, 14-19.

Rudel, R. A., and Brody, J. G. (2001). Identification of selected hormonally active agents and animal mammary carcinogens in commercial and residential air and dust samples. Journal of Air & Waste Management Association 51, 499-513.

Rudel, R. A., Camann, D. E., Spengler, J. D., Korn, L. R., and Brody, J. G. (2003). Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. Environmental Science and Technology 37, 4543-4553.

Schettler, T. (2006). Human exposure to phthalates via consumer products. International Journal of Andrology 29, 134-139.

Snedeker, S. M. (2006). Chemical exposure in the workplace; Effect on breast cancer risk among women. American Association of Occupational Health Nurses Journal 54, 270-279.

Spaeth, K. R. (2000). Don't hold your breath: personal exposure to volatile organic compounds and other toxin in indoor air and what's (not) being done about it. Preventative Medicine 31, 631-637.

Yang, L., Parkin, D. M., Ferlay, J., Li, L., and Chen, Y. (2005). Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiology, Biomarkers & Prevention 14, 243-250.

Searching for Answers: "Unpacking" How Socioeconomic Status Affects Breast Cancer Survivorship and Risk The Ribbon

Searching for Answers: "Unpacking" How Socioeconomic Status Affects Breast Cancer Survivorship and Risk
The Ribbon