Breast Cancer and the Environment A Life Course Approach (2012) / Chapter Skim
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7 Recommendations for Future Research
7 Recommendations for Future Research
Pages 325-346
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From page 325... ...
First, the scientific community is faced with conflicting and inconclusive results from past studies of some risk factors. Second, growing knowledge of the complex biology of breast cancer suggests a need to reframe hypotheses by focusing more on exposures in early life, examining associations with tumors of specific types, and considering mechanistically driven gene–environment interactions.
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From page 326... ...
Although information about some early life events, such as age when first giving birth or age at menarche, can be reliably retrieved, few studies have collected information on nonreproductive environmental exposures that may influence the occurrence of clinically detectable breast cancer many decades later. To address gaps in knowledge about the origins of breast cancer, the committee determined that research should increasingly focus on the influence of environmental factors during potential windows of susceptibility over the life course.
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From page 327... ...
Other work to aid investigation of environmental influences on breast cancer risk includes • identifying cellular, biochemical, or molecular biomarkers of early events leading to breast cancer and validating their predictive value for future risk for breast cancer; • determining whether intermediate endpoints, such as indicators of breast development or peak height growth velocity, are valid and predictive biomarkers of risk for breast cancer so that research can
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From page 328... ...
TARGETING SPECIFIC CONCERNS Rationale: From its examination of evidence on a selection of environmental factors, the committee sees particular benefit in further research to clarify the mechanisms underlying breast cancer. Recommendation 2: Breast cancer researchers and research funders should pursue research to increase knowledge of mechanisms of action of environmental factors for which there is provocative, but as yet inconclusive, mechanistic, animal, life course, or human health evi dence of a possible association with breast cancer risk.
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From page 329... ...
More research is needed to understand the degree to which mutagenic chemicals, such as polycyclic aromatic hydrocarbons (PAHs) , benzene, and ethylene oxide, acting alone or in combination with other exposures at specific life stages, may contribute to breast cancer risk at current levels of exposure.
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From page 330... ...
Changes in the typical workplace and the presence of more women in the workforce, both in the United States and internationally, make it appropriate to revisit occupational studies as a possible means to identify some exposures that increase risk for breast cancer. These studies should account for not only comparisons of breast cancer incidence associated with various work assignments or job titles, but also the distribution of known breast cancer risk factors among workers to ensure that the analyses of exposure-related risk are not confounded by differences among types of workers in the prevalence of these other known risk factors.
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From page 331... ...
Recommendation 4: Breast cancer and exposure assessment researchers and research funders should pursue research to improve methodologies for measuring, across the life course, personal exposure to and biologi cally effective doses of environmental factors that may alter risk for or susceptibility to breast cancer. Such research should encompass • improving measurements in the environment and assessing varia tion over time and space;
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From page 332... ...
Chapter 6 sets forth a series of steps that can be taken by various groups and in various settings to reduce exposures to ionizing radiation and therefore reduce risks for breast and other cancers. However, many unknowns remain about the best ways to achieve these reductions.
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From page 333... ...
Recommendation 6: Breast cancer researchers and research funders should pursue prevention research in humans and animal models to develop strategies to alter modifiable risk factors, and to test the effec tiveness of these strategies in reducing breast cancer risk, including timing considerations and population subgroups likely to benefit most. Particular aspects of prevention that require attention include • when weight loss is most likely to be beneficial in reducing risk for postmenopausal breast cancer; • effective strategies for achieving and maintaining weight loss in different risk groups; • effective and sustainable methods to prevent obesity; • the feasibility of interventions in early life and development that may influence breast cancer risk in adult life such as prevent ing childhood obesity, increasing physical activity, and minimizing exposures to potentially harmful environmental carcinogens; • approaches to prevention that respond to the differing breast can cer experience of various racial and ethnic groups; and • dissemination and adoption of effective prevention strategies.
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From page 334... ...
Recommendation 7: Breast cancer researchers and research funders should pursue continued research into new breast cancer chemopreven tion agents that have minimal risk for other adverse health effects. This work should include efforts to identify chemopreventive approaches for hormone receptor negative breast cancer.
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From page 335... ...
Thus results of bioassays of hormonally active agents are confounded when mammary tumors are increased concomitantly with constant estrus in the treated rats. With the insensitivity of mice, negative results from tests in mice are not necessarily a reliable indicator of lack of mammary carcinogenicity.
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From page 336... ...
The development of these protocols should address several issues, including the following: • potential differences in sensitivity to carcinogenic effects and dur ing different life stages; • the appropriateness and limitations of the rodent strains and spe cies used for testing, and potential alternatives; • the frequency, magnitude, and route of dosing, and the possible need for alternative protocols that provide improved relevance for predicting human risk; • the utility of genetically engineered mouse models, which show promise for studying breast tumor formation and progression and the effectiveness of treatments; and • standard practices for conducting and reporting results of animal studies. This work will probably also require targeted mechanistic and pharmacokinetic studies to assess appropriate dosing levels in test protocols to better address human exposure circumstances, including the influence of life stage, genetic variability, and multiple chemical exposures.
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From page 337... ...
Because breast cancer is a major contributor to morbidity among women, these tests should address pathways that underlie the basic mechanisms of breast cancer -- mutagenesis, estrogen receptor signaling, epigenetic programming, growth promotion via mitogenic cell signaling, and modulation of immune functioning -- with particular attention to cell types and environments relevant to breast cancer. They should also take into account alterations at the whole-organ level, and they should be relevant to typical human exposures, which often occur at low doses and as mixtures.
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From page 338... ...
It is also critical for the understanding of epidemiologic and in vivo and in vitro experimental research results on the health effects of chemical mixtures that are characteristic of human environmental exposures. Identifying Breast Cancer Risks Associated with Hormonally Active Pharmaceutical Products The committee sees a need to ensure that mechanisms for detection and assessment of breast cancer risks associated with use of drugs regulated by FDA are adequate.
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From page 339... ...
. Although the increased risk of breast cancer that is associated with use of combination hormone therapies, including oral contraceptives, declines after treatment stops, women should be aware of the full range of potential harms as well as the benefits when they decide whether to use any form of hormone therapy, including those touted as safe because they are "bioidentical" or "natural." New Approaches to Testing Hormonally Active Candidate Pharmaceuticals Rationale: Given the evidence for hormonal influences on the development of breast cancer, the committee is concerned that testing required to gain marketing approval for various hormonally active pharmaceuticals that are already on the market or that are being developed does not adequately address the potential impact on the risk for breast cancer.
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From page 340... ...
These tests may also prove useful in testing environmental chemicals. Postmarketing Studies of Hormonally Active Products Rationale: With the demonstration that use of certain hormonally active prescription drugs is associated with an increased risk of breast cancer and other adverse health effects, it is important to investigate whether use of other hormonally active drugs is also associated with increased risk.
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From page 341... ...
Systematic modeling approaches are needed to refine the estimates of the proportion of breast cancer in the United States and other countries that can be attributed to known factors, especially modifiable factors. Substantial proportions of the increase in breast cancer incidence rates in the United States over the past century, and of the differences in rates of breast cancer between less developed countries and more affluent countries, are probably due in large part to differences over time and between countries in the prevalence of established breast cancer risk factors (e.g., age at menarche, age at first birth, parity, use of menopausal hormone therapy, physical activity, weight and weight change)
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From page 342... ...
determine the propor tion of the total temporal and geographic differences in breast cancer rates that can be plausibly attributed to established risk factors, and (3) develop modeling tools that allow for calculation of breast cancer risk, in both absolute and relative terms, with the goal of assessing potential risk reduction strategies, at both personal and public health levels.
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From page 343... ...
Meaningful differences in risk need to be effectively communicated to the public, health care providers, and policy makers so that limited funds can be invested in the most promising research and intervention strategies. Recommendation 13: Breast cancer researchers and research funders should pursue research to identify the most effective ways of commu nicating accurate breast cancer risk information and statistics to the general public, health care professionals, and policy makers.
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From page 344... ...
Important targets for research are the biologic significance of life stages at which environmental risk factors are encountered, what steps may counter their effects, when preventive actions can be most effective, and whether opportunities for prevention can be found for the variety of forms of breast cancer.
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From page 345... ...
2001. Communicating breast cancer risks to women using different formats.
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