Invited Commentary: Extremely Low-Frequency Magnetic Fields and Breast Cancer Now It Is Enough!

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1 American Journal of Epidemiology The Author Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please Vol. 178, No. 7 DOI: /aje/kwt160 Advance Access publication: September 15, 2013 Invited Commentary Invited Commentary: Extremely Low-Frequency Magnetic Fields and Breast Cancer Now It Is Enough! Maria Feychting* * Correspondence to Dr. Maria Feychting, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE Stockholm, Sweden ( maria.feychting@ki.se). Initially submitted February 13, 2013; accepted for publication May 20, Research on an association between extremely low frequency (ELF) magnetic fields and breast cancer has been conducted since the 1980s, based on the hypothesis that ELF fields suppress melatonin production and melatonin protects against breast cancer development. In this issue of the Journal, Li et al.(am J Epidemiol. 2013;178(7): ) present a well-designed study on occupational exposure to ELF fields and breast cancer that adds to the already large pool of data that has not supported the hypothesis. Over time, the quality and statistical power of studies within this research area have increased considerably, and advances in exposure assessment have reduced exposure misclassification. The evidence is consistently negative. A World Health Organization health risk assessment concluded in 2005 that the evidence from experimental and epidemiologic studies is sufficient to give confidence that ELF magnetic fields do not cause breast cancer. The new study adds even more confidence to this conclusion. We should now focus our time and research resources on more promising hypotheses, the results of which could make a difference for public health and advance science. Further epidemiologic studies on ELF fields and breast cancer are likely to have little new knowledge to add. breast neoplasms; electromagnetic fields; risk assessment Abbreviations: ELF, extremely low frequency; WHO, World Health Organization. The hypothesis that exposure to power-frequency (50 60 Hertz) magnetic fields increases the risk of breast cancer was put forward in the 1980s (1). This research question attracted attention primarily because it suggested a potentially plausible biological mechanism, which had not been the situation for similar research on other outcomes, such as childhood leukemia, in which public health concern was the main driving force. The idea was based on the hypotheses that magnetic fields could suppress melatonin production in the same way as light at night and that high melatonin levels protect against the development of breast cancer. Some early experimental and epidemiologic studies indicated support for the hypothesis, but they had limitations in the design and/or statistical power, and positive findings in the epidemiologic studies were mainly confined to subgroups. Since then, a large number of experimental and epidemiologic studies have addressed this question (2, 3) using considerably improved study designs, including better controlled experiments and larger epidemiologic studies with improvements in exposure assessment and other design features, and some had enough power to adequately address previous subgroup findings (4). Table 1 displays the main results of the epidemiologic studies on ELF magnetic fields and female breast cancer, grouped into residential exposure, exposure to electric bed heating devices, and occupational exposure. Overall, the studies have not been able to confirm the few early positive findings, and thus do not support the hypothesis that ELF magnetic fields increase the risk of breast cancer. In this issue of the Journal, Li et al.(5) provide additional evidence concerning the hypothesis about an association between ELF magnetic fields and breast cancer risk. Theirs is a welldesigned study nested within a cohort of textile workers, an industry known to have a large proportion of highly exposed workers. Exposure assessment was better than in previous studies, with comprehensive measurements of magnetic field levels for all possible combinations of work types and manufacturing processes that resulted in a detailed job exposure 1046

2 Magnetic Fields and Breast Cancer 1047 Table 1. Studies of Female Breast Cancer in Relation to Various Sources of Extremely Low-Frequency Magnetic Field Exposure First Author, Year (Reference No.) Exposure Estimate/Subgroup Studied Exposure Category RR 95% CI Verkasalo, 1996 (10) Li, 1997 (11) Coogan, 1998 (12) Feychting, 1998 (13) Davis, 2002 (14) Calculated cumulative exposure from residential Calculated yearly average residential Residential proximity from power line or substation Calculated yearly average residential Percent of nighttime measurements >0.2 µt Residential Exposure Referent = general SIR population <0.20 µt , µt , µt , µt , µt , µt , 1.5 >0.2 µt , 1.3 Within 152 m , µt , µt , 1.5 0% 1.0 <0.7% , % 8.9% , % 58% , % , 1.8 London, 2003 (15) Mean nighttime magnetic field µt , µt , µt , µt , 3.0 Schoenfeld, 2003 (16) 24-hour bedroom magnetic field <0.041 µt µt , µt , µt , 1.4 Kliukiene, 2004 (17) Time-weighted average <0.05 µt µt , µt , 1.83 Elliott, 2013 (18) Calculated fields from residential µt , µt , µt , µt , µt , 1.51 Electric Blankets/Heating Devices Vena, 1991 (19) Postmenopausal women Ever use , 1.2 Vena, 1994 (20) Premenopausal women Ever use , 1.7 Coogan, 1998 (12) Pre- and postmenopausal women Regular use , 1.4 Gammon, 1998 (21) Premenopausal women Ever use , 1.2 Postmenopausal women Ever use , 1.4 Laden, 2000 (22) Premenopausal women Ever use , 1.7 Postmenopausal women Ever use , 1.2 Zheng, 2000 (23) Pre- and postmenopausal women Ever use , 1.1 McElroy, 2001 (24) Mostly postmenopausal women Ever use , 1.1 Davis, 2002 (14) Pre- and postmenopausal women Ever use , 1.3 Kabat, 2003 (25) Premenopausal women in LIBCSP Ever use , 1.6 Postmenopausal women in LIBCSP Ever use , 1.3 Premenopausal women in EBCLIS Ever use , 1.9 Postmenopausal women in EBCLIS Ever use , 1.3 Zhu, 2003 (26) Pre- and postmenopausal women Ever use , 2.2 Table continues matrix that could be applied to participants complete work histories. This should have reduced nondifferential exposure misclassification and minimized potential attenuation of risk estimates that could have masked a true association. As in most previous studies, results in this new study provided no indication of an increased risk of breast cancer associated with exposure to ELF magnetic fields. A limitation of the study is the lack of information about the estrogen receptor status tumors,

3 1048 Feychting Table 1. Continued First Author, Year (Reference No.) Exposure Estimate/Subgroup Studied Exposure Category RR 95% CI Coogan, 1998 (12) Van Wijngaarden, 2001 (27) Håkansson, 2002 (28) Labreche, 2003 (29) Kliukiene, 2003 (30) Kliukiene, 2004 (17) Forssen, 2005 (4) McElroy, 2007 (31) Johansen, 2007 (32) Ray, 2007 (33) Occupational history and expert judgment categories: no, medium, or high Job exposure matrix, time-weighted average Geometric mean of average workday measurements Occupational history, duration of time, and 4 exposure categories assessed by an occupational hygienist Mainly workers onboard merchant ships; ELF field spot measurements Job history, censuses every 10th year, and expert judgment (time above 0.10 µt in 3 categories no. of years) Job history, censuses taken every fifth year, and job exposure matrix based on measurements in women, timeweighted average; n = 20,400 cases Occupational history and expert judgment categories: no, medium, or high Cohort of electric utility workers; job exposure matrix Cohort of female textile workers; length electromagnetic field exposure as some early studies suggested that the effect was confined to estrogen receptor positive breast cancer (2). On the other hand, with no overall increase in risk, a raised risk in one subgroup must be accompanied bya reduced risk in another, which lacks biological plausibility and is not to be expected based on the hypothesized biological mechanism. In addition, other studies have provided evidence that considerably weaken the hypothesis that an effect would depend on estrogen receptor status (4). In 2001, the International Agency for Research on Cancer evaluated the carcinogenicity of ELF electric and magnetic fields (6). ELF magnetic field exposure was classified as possibly carcinogenic based on the evidence from epidemiologic studies of childhood leukemia that consistently had reported an increased risk associated with high residential magnetic field exposure. For other cancers, including breast cancer, the evidence was considered inadequate. At the time, few studies on breast cancer were available, but many epidemiologic studies were underway. A few years later, in 2005, the World Health Organization (WHO) convened a working group to perform a full health Occupational Exposure No exposure 1.0 Medium exposure , 1.7 High exposure , µt-years 1.0 > µt-years , 1.8 > µt-years , 1.5 > µt-years , 1.4 >2.43 µt-years , 1.7 <0.164 µt µt , µt , 1.3 >0.530 µt , 1.5 Lifetime exposure at medium or high level per 6,000 h Job title: radio and telegraph operators , , 1.58 < , , 1.40 <0.10 µt µt , µt , µt , 1.10 No exposure 1.0 Low exposure , 1.13 Medium exposure , 1.26 High exposure , 1.53 <0.1µT µT , µT , years 1.0 <5 years , <10 years , <20 years , years , 1.01 Abbreviations: CI, confidence interval; EBCLIS, Electromagnetic Fields and Breast Cancer on Long Island Study; ELF, extremely low frequency; LIBCSP, Long Island Breast Cancer Study Project; RR, relative risk; SIR, standardized incidence ratio. risk assessment of ELF fields (3). Their conclusion about childhood leukemia and exposure to ELF electric and magnetic fields was the same as the one from the International Agency for Research on Cancer; however, the WHO working group made much stronger statements about breast cancer. During the time since the review by the International Agency for Research on Cancer, a considerable number of new epidemiologic studies of magnetic fields and female breast cancer had been published: 5 on occupational exposure (among them 2 cohort studies), 4 on residential exposure, and 4 on electric bed-heating devices. The overwhelming evidence from these studies did not support an effect of ELF magnetic fields on breast cancer risk, and in addition, evidence from experimental studies did not support the hypothesis that ELF magnetic fields suppress melatonin production. The WHO working group concluded about the new epidemiologic studies, These studies are larger than the previous ones and less susceptible to bias, and overall are negative. With these studies, the evidence for an association between ELF exposure and the risk of breast cancer is weakened considerably and does not support an association of this kind (3, p. 307).

4 Magnetic Fields and Breast Cancer 1049 In the final conclusions, the working group stated that, in some cases (for example, for cardiovascular disease or breast cancer) the evidence is sufficient to give confidence that magnetic fields do not cause the disease (3, p. 351). Since the WHO health risk assessment, only a few new studies on exposure to ELF magnetic fields and breast cancer have been published, and most of them focused on occupational exposure (Table 1). Concluding paragraphs in epidemiologic articles frequently include statements about the need for future research, often rightfully so because firm conclusions cannot be drawn on single studies and a solid scientific basis is needed for valid health risk assessment. There is a time, however, when the scientific data base has become so large and consistent that additional epidemiologic studies cannot change the overall conclusions unless completely new ideas or experimental findings give clues about biological mechanisms that would void approaches taken in previous studies. This is the time when we need to ask ourselves what the additional contribution from a new epidemiologic study would be to the overall pool of data. Despite the quite strong statements made in the WHO health risk assessment (3), new epidemiologic studies on ELF magnetic fields and breast cancer continue to be published many years later without new mechanistic evidence or seminal experimental findings. Savitz (7) discussed various motives for continuing to perform epidemiologic studies in areas in which there is little new scientific knowledge to gain, calling it the etiology of epidemiologic perseveration (7, p. 1). The rationale behind additional research on the potential health effects of electromagnetic fields fits several of the characteristics described by Savitz, the most prominent of which is still likely to be public concern about exposures that are ubiquitous in society. The level of public concern leads to greater availability of research funds. For childhood leukemia, new epidemiologic studies have tended to confirm the weak association that led to the classification of ELF magnetic fields as possibly carcinogenic (8), but they have not provided further insight into potential mechanisms or other aspects of the relationship. Recently, Schmiedel and Blettner (9) suggested that epidemiologic research has come to an impasse concerning ELF fields and childhood leukemia and cannot provide any further evidence unless new ideas or mechanistic evidence emerge. More of the same will not move the science within this area forward. Similar arguments can be put forward regarding breast cancer, with the difference being that the mounting evidence speaks strongly against an association. It is very difficult for epidemiology to prove the negative; the data cannot cover all potentially susceptible subgroups or combinations of exposures, and there will always be some degree of exposure misclassification or other bias, even in the most well-designed studies. Nevertheless, as data amass with improved methods designed to address weaknesses identified in previous research, the weight of the evidence can make us more and more confident that an effect of the exposure is lacking, as is reflected by the statement made in the WHO Environmental Health Criteria document (3). With the new well-designed study on occupational ELF exposure and breast cancer in this issue of the Journal (5), it maybetime to conclude thatnowit isenough.weshouldfocus our time and research resources on more promising hypotheses, the results of which can make a difference for public health and advance science. With the existing knowledge about biophysical mechanisms and consistent epidemiologic evidence, we can be confident that exposure to ELF magnetic fields does not cause breast cancer. Further epidemiologic studies on ELF fields and breast cancer will have little new knowledge to add. ACKNOWLEDGMENTS Author affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (Maria Feychting). Conflict of interest: none declared. REFERENCES 1. Stevens RG. Electric power use and breast cancer: a hypothesis. Am J Epidemiol. 1987;125(4): Feychting M, Forssen U. Electromagnetic fields and female breast cancer. 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