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Introduction to environmental causes of breast cancer
S58
Abstracts / Toxicology Letters 259S (2016) S4–S62
drugs, mainly the anorexiant sibutramine frequently in combination with the laxative phenolphthalein, two medicines withdrawn from the market. In both categories, the amounts of drugs were erratic, from traces to high amounts. A follow-up over time of several DS revealed that manufacturers make changes in their chemical composition. Lack of quality indicated poor manufacturing practices. Conclusions: The fraudulent addition of synthetic compounds to DS constitutes a significant threat to consumer health because these products may contain substances whose toxicity has never been assessed and whose interaction with prescribed medicines may be unpredictable. In the search for adulterants, 1 H NMR is very attractive mainly because it is non-selective, providing global information and structural information in a single analysis. This study demonstrated that NMR could be introduced in QC laboratory as a routine screening tool for unveiling adulteration, and highlighted the need for more effective QC of purported herbal DS. Financial support: French National Agency for the Safety of Medicines and Health Products (ANSM, project AAP-2012-082). http://dx.doi.org/10.1016/j.toxlet.2016.07.140 Symposia S32: Environmental causes of breast cancer S32-1 Introduction to environmental causes of breast cancer M.E. Cebrian Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico DF, Mexico Breast cancer (BC) incidence is increasing worldwide, although with a wide incidence range among countries. In addition to genetic background, it is likely that differences in environmental exposures and conditions throughout the world may be related to the wide differences in incidence. However, information about specific chemical exposures and BC risk is limited. It may be difficult to identify and measure exposures, especially if relevant exposures occurred well in the past and/or the timing of such exposures is unclear. In addition, tracing multiple and potentially interacting causes of BC is difficult. Furthermore, some aspects of the biology of female breast development and the role of chemical exposures in critical windows of development are not fully understood. The timing of a variety of environmental exposures may be important in directly affecting BC risks, or in acting indirectly by influencing the developmental events. Although, many questions remain regarding the contributions of environmental factors to BC risk, evidence suggests that women may have some opportunities to reduce their risk through personal actions. The aim of this symposium is to discuss some of the challenges involved in determining which environmental exposures may influence BC severity and rates. http://dx.doi.org/10.1016/j.toxlet.2016.07.142
S32-2 Breast cancer and the environment: The U.S. Institute of Medicine 2011 Report C.L. Walker 1 , I. Hertz-Picciotto 2 1
Texas A&M Institute of Biosciences and Technology, Houston, Texas, USA 2 Department of Public Health Sciences, University of California, Davis, California, USA Introduction: Breast cancer accounts for substantial morbidity among women throughout the world, with an estimated 1.7 million new cases worldwide in 2012. Incidence and mortality began to noticeably rise in western countries in the early 1980s, leading to concerns about the environmental causes. Objective: The Institute of Medicine (IOM) was commissioned by the Susan G. Komen for the Cure® and its Scientific Advisory Board, to: (1) assess current evidence on the contribution of environmental exposures, alone or in combination with genetic factors, to the risk of developing breast cancer; (2) review the challenges in investigating potential environmental contributions; (3) explore evidence-based actions that women might take to reduce the risk of breast cancer; and (4) recommend research directions. Methods: A qualitative review was undertaken by a panel of experts covering molecular carcinogenesis, epidemiology, toxicology, exposure science, cancer prevention, clinical studies, biostatistics, and risk assessment, and also including a representative from the breast cancer advocacy community. This review examined current evidence on selected factors that illustrate various environmental agents and conditions that may be more amenable to modification. The peer-reviewed literature was screened for toxicologic, mechanistic and epidemiologic studies, with a focus on review papers for risk factors that have been wellstudied. The panel also considered new molecular discoveries that may change the way in which carcinogenesis is conceptualized, addressed what types of actions women can take to reduce their individual risk, and recommended future research directions. Results: For some of these factors, epidemiologic studies consistently support associations with increased risk for breast cancer (e.g., ionizing radiation, combination hormone therapy, greater postmenopausal weight) or reduced risk (e.g., more physical activity). For many other factors, however, the epidemiologic evidence is more limited, contradictory, or absent (e.g., parabens). Animal or mechanistic studies sometimes add support to epidemiologic evidence or suggest biologic plausibility in the absence of human evidence. Understanding of the complexity of breast cancer and its relation to environmental exposures is growing. Key gaps in knowledge were identified, including the biologic significance of life stage at the time an exposure is encountered; optimal methods for assessing some exposures, how to integrate analysis of genetic and environmental influences; synergies among multiple low-level chemical exposures; and interpretation of findings from studies in animals and in vitro systems. Conclusions: With regard to exposure reduction strategies, some personal actions were deemed to potentially lower a woman’s risk of breast cáncer, despite uncertainty in the evidence. These include: avoiding unnecessary medical radiation, or increasing physical activity. With regard to future directions for research, several recommendations were put forward to enhance understanding of the early origins of breast cáncer and to focus attention on preventive interventions and effective risk communication. Financial support: The IOM Report was commissioned by the Susan G. Komen Foundation for the Cure. As a member of the IOM
Abstracts / Toxicology Letters 259S (2016) S4–S62
drugs, mainly the anorexiant sibutramine frequently in combination with the laxative phenolphthalein, two medicines withdrawn from the market. In both categories, the amounts of drugs were erratic, from traces to high amounts. A follow-up over time of several DS revealed that manufacturers make changes in their chemical composition. Lack of quality indicated poor manufacturing practices. Conclusions: The fraudulent addition of synthetic compounds to DS constitutes a significant threat to consumer health because these products may contain substances whose toxicity has never been assessed and whose interaction with prescribed medicines may be unpredictable. In the search for adulterants, 1 H NMR is very attractive mainly because it is non-selective, providing global information and structural information in a single analysis. This study demonstrated that NMR could be introduced in QC laboratory as a routine screening tool for unveiling adulteration, and highlighted the need for more effective QC of purported herbal DS. Financial support: French National Agency for the Safety of Medicines and Health Products (ANSM, project AAP-2012-082). http://dx.doi.org/10.1016/j.toxlet.2016.07.140 Symposia S32: Environmental causes of breast cancer S32-1 Introduction to environmental causes of breast cancer M.E. Cebrian Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico DF, Mexico Breast cancer (BC) incidence is increasing worldwide, although with a wide incidence range among countries. In addition to genetic background, it is likely that differences in environmental exposures and conditions throughout the world may be related to the wide differences in incidence. However, information about specific chemical exposures and BC risk is limited. It may be difficult to identify and measure exposures, especially if relevant exposures occurred well in the past and/or the timing of such exposures is unclear. In addition, tracing multiple and potentially interacting causes of BC is difficult. Furthermore, some aspects of the biology of female breast development and the role of chemical exposures in critical windows of development are not fully understood. The timing of a variety of environmental exposures may be important in directly affecting BC risks, or in acting indirectly by influencing the developmental events. Although, many questions remain regarding the contributions of environmental factors to BC risk, evidence suggests that women may have some opportunities to reduce their risk through personal actions. The aim of this symposium is to discuss some of the challenges involved in determining which environmental exposures may influence BC severity and rates. http://dx.doi.org/10.1016/j.toxlet.2016.07.142
S32-2 Breast cancer and the environment: The U.S. Institute of Medicine 2011 Report C.L. Walker 1 , I. Hertz-Picciotto 2 1
Texas A&M Institute of Biosciences and Technology, Houston, Texas, USA 2 Department of Public Health Sciences, University of California, Davis, California, USA Introduction: Breast cancer accounts for substantial morbidity among women throughout the world, with an estimated 1.7 million new cases worldwide in 2012. Incidence and mortality began to noticeably rise in western countries in the early 1980s, leading to concerns about the environmental causes. Objective: The Institute of Medicine (IOM) was commissioned by the Susan G. Komen for the Cure® and its Scientific Advisory Board, to: (1) assess current evidence on the contribution of environmental exposures, alone or in combination with genetic factors, to the risk of developing breast cancer; (2) review the challenges in investigating potential environmental contributions; (3) explore evidence-based actions that women might take to reduce the risk of breast cancer; and (4) recommend research directions. Methods: A qualitative review was undertaken by a panel of experts covering molecular carcinogenesis, epidemiology, toxicology, exposure science, cancer prevention, clinical studies, biostatistics, and risk assessment, and also including a representative from the breast cancer advocacy community. This review examined current evidence on selected factors that illustrate various environmental agents and conditions that may be more amenable to modification. The peer-reviewed literature was screened for toxicologic, mechanistic and epidemiologic studies, with a focus on review papers for risk factors that have been wellstudied. The panel also considered new molecular discoveries that may change the way in which carcinogenesis is conceptualized, addressed what types of actions women can take to reduce their individual risk, and recommended future research directions. Results: For some of these factors, epidemiologic studies consistently support associations with increased risk for breast cancer (e.g., ionizing radiation, combination hormone therapy, greater postmenopausal weight) or reduced risk (e.g., more physical activity). For many other factors, however, the epidemiologic evidence is more limited, contradictory, or absent (e.g., parabens). Animal or mechanistic studies sometimes add support to epidemiologic evidence or suggest biologic plausibility in the absence of human evidence. Understanding of the complexity of breast cancer and its relation to environmental exposures is growing. Key gaps in knowledge were identified, including the biologic significance of life stage at the time an exposure is encountered; optimal methods for assessing some exposures, how to integrate analysis of genetic and environmental influences; synergies among multiple low-level chemical exposures; and interpretation of findings from studies in animals and in vitro systems. Conclusions: With regard to exposure reduction strategies, some personal actions were deemed to potentially lower a woman’s risk of breast cáncer, despite uncertainty in the evidence. These include: avoiding unnecessary medical radiation, or increasing physical activity. With regard to future directions for research, several recommendations were put forward to enhance understanding of the early origins of breast cáncer and to focus attention on preventive interventions and effective risk communication. Financial support: The IOM Report was commissioned by the Susan G. Komen Foundation for the Cure. As a member of the IOM