Environmental Exposures That May Be Relevant For Breast Cancer Etiology And Progression
Based on laboratory studies, a number of potential breast cancer carcinogens have been identified that also are known environmental contaminants . More than 30 mammary carcinogens in animals and at least twice that many human carcinogens have been characterized to date.- Many of these chemicals are more likely to be encountered in an industrial environment than in settings that most women experience daily. With the advent of the so-called endocrine disruptor phenomenon, hormonally active environmental chemicals have been targeted as potential risk factors for reproductive toxicity, including breast cancer. In a recent survey, 86 potential mammary toxins were identified and measured in household dust and air, including 9 known mammary carcinogens and 77 hormonally active agents or closely related compounds. Of these, > 30% were detected at least once in a pilot study of 3 homes . A study of occupational exposure to these compounds found approximately 30% of women to have hormonally active exposures in their workplace.
Shirley Plahovinsak: More Va Research Needed On Breast Cancer
Two U.S. Senators want more Department of Veterans Affairs action for female veterans on breast cancer research caused by exposure to toxic burn pits. On October 29, 2021, Senators Amy Klobuchar and Joni Ernst joined together to issue a letter to Departments of Defense and the VA requesting policy changes and more research on breast cancer.
Both Senators want the DoD and the VA to focus their research efforts on the linkage between the female veterans exposure to the toxic open burn pits used in Afghanistan and Iraq and breast cancer.
Open air burn pits, normally located near military bases, were used to incinerate jet fuel, medical waste, plastics, obsolete equipment, munitions and other disposable items or supplies. The toxic airborne fumes released by these huge fires have caused veterans to contract cancer, respiratory issues and lung diseases.
The National Institutes of Health has already stated there is growing evidence that supports the concept of breast cancer being caused by toxic environmental factors. According to the NIH, female veterans are estimated to be 40 percent more likely to develop breast cancer than the general female population.
However, there is no published research directly linking toxic burn pit exposure to instances of breast cancer. The Senators letter stated, We must better understand and address the relationship between burn pit exposure and the health needs of our military.
Increasing Evidence Links Air Pollution With Breast Cancer
NIEHS epidemiologist Alexandra White, Ph.D., conducts research with potential for significant public health impact.
Given the high incidence of breast cancer and the widespread nature of environmental exposures, such as air pollution, our research has potential for substantial public health impact, said Alexandra White, Ph.D., who leads the Environment and Cancer Epidemiology group at NIEHS.
Breast cancer accounts for 30% of newly diagnosed invasive cancers in women, reports the American Cancer Society. Furthermore, population-based data show significant, steady increases in breast cancer from 1935 to 2015, particularly among younger women .
The condition has known or suspected links to many environmental factors.
Those factors need greater consideration as contributors to these higher rates, said White. There has not been significant progress in reducing breast cancer incidence with the risk factors that have been identified.
The conundrum for scientists and health care practitioners is that even established risk factors, such as postmenopausal obesity and alcohol intake, have small effects on the overall chance of developing breast cancer.
Specific Dietary Fatty Acids
Although many claims have been made in popular literature there is no solid evidence linking specific fats to breast cancer.
A study published in 2001 found higher levels of monounsaturated fatty acids MUFAs in the erythrocyte membranes of postmenopausal women who developed breast cancer.
That same study discussed that a diet high in MUFAs is not the major determinant of erythrocyte membrane MUFAs, where most oleic acid in mammalian tissue is derived from the saturated stearic acid residue. Where key conversion is controlled by the Delta9-desaturase, which also regulates the transformation of the other common saturated fatty acids . The study discussed that fat content of the diet has an important effect on Delta9-d activity, while high levels of SFAs increase Delta9-d activity by twofold to threefold, whereas polyunsaturated fatty acids decrease.
This conclusion was partially contradicted by a latter study, which showed a direct relation between very high consumption of omega-6 fatty acids and breast cancer in postmenopausal women.
Risk Factors For Breast Cancer
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Risk factors for breast cancer may be divided into preventable and non-preventable. Their study belongs in the field of epidemiology. Breast cancer, like other forms of cancer, can result from multiple environmental and hereditary risk factors. The term “environmental”, as used by cancer researchers, means any risk factor that is not genetically inherited.
For breast cancer, the list of environmental risk factors includes the individual person’s development, exposure to microbes, “medical interventions, dietary exposures to nutrients, energy and toxicants, ionizing radiation, and chemicals from industrial and agricultural processes and from consumer products…reproductive choices, energy balance, adult weight gain, body fatness, voluntary and involuntary physical activity, medical care, exposure to tobacco smoke and alcohol, and occupational exposures, including shift work” as well as “metabolic and physiologic processes that modify the body’s internal environment.” Some of these environmental factors are part of the physical environment, while others are primarily part of the social, cultural, or economic environment.
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Leaders Of Breast Cancer Advocacy Organizations Are Concerned About Environmental Links
Focus groups and interviews gave further insights into how breast cancer organizations across the country have incorporated environmental topics into their work. While the majority of U.S. breast cancer organizations do not emphasize environmental factors when presenting information online, almost all focus group participants and many of the interviewees were concerned about possible links between environmental chemicals and breast cancer. They were especially concerned about pesticides, air pollution, and consumer products. For example, one focus group participant stated,
I live in a really agriculture rich rural area and Im confident that a lot of our cancer diagnoses, not just for breast cancer but for many, many kinds of cancer, are directly related to the amount of chemicals that are being sprayed.
Another followed up, saying,
Im extremely concerned as well about what were using, and while I have to admit that Ive not made any big changes as some of you all have by going to more natural products, I do read a lot more labels now So I would like to get to a point where we wouldnt have to worry about the dangers of the products that we use routinely in our home.
The Role Of Environmental Chemicals
In the aftermath of World War II, industry began producing large quantities of synthetic chemicals including pesticides, plastics, solvents, and other substances. These chemicals made their way into our everyday products and into our environment, with little regard for safety. Since then, tens of thousands of chemicals have been produced and sold on the market, the vast majority of which have not been tested for their effects on human health.
Over the last couple of decades, studies show exposure to certain chemicals can contribute to the development of breast cancer. In a landmark study published in 2007 in the journal Cancer, researchers at Silent Spring identified 216 chemicals that cause mammary tumors in animals. About half of these are chemicals women are routinely exposed to in their everyday lives.
Meanwhile, laboratory studies have uncovered several biological mechanisms by which chemicals can lead to breast cancer: Chemicals can damage DNA causing uncontrolled cell growth they can act as tumor promoters that make cells grow and they can change the way the breast develops, leaving it more vulnerable to carcinogens.
In a study in 2003, we detected dozens of EDCs in air and dust inside the home, demonstrating for the first time that consumer products are major source of indoor air pollutants.
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Breast Cancer And Environmental Risk Factors: An Appraisal Of The Scientific Evidence
volume 10, Article number: P45
With a few exceptions, the number of new breast cancer cases among women is increasing in almost all western countries. Although lifestyle, life choices, genetics and the diet are shown to contribute to the increase in breast cancer, the sheer number of newly diagnosed cases cannot solely be explained by these factors. The present review aims to evaluate evidence that environmental factors, including chemical exposure, also play a role.
Studies among identical twins have shown that the most important contributor to the causation of breast cancer is the environment not shared by the pair, even under circumstances where the genetic predisposition is very similar. Similarly, in families with a heritable predisposition to breast cancer, time of birth, physical activity and obesity can profoundly influence risk.
There is overwhelming evidence that oestrogens are strong determinants of breast cancer risks. This is not limited to natural oestrogens formed in a woman’s body, but extends to synthetic hormones used as pharmaceuticals, such as those used for the alleviation of menopausal symptoms. The demonstration of breast cancer risks from oestrogen-only and, more pronounced, from combined oestrogenprogesterone regimens is a case in point. Very recent decreases in breast cancer incidence in the USA and in parts of Germany could even be linked to a dropping off of hormone therapy use.
How Can Exposures To Carcinogens Be Limited
In the United States, regulations have been put in place to reduce exposures to known carcinogens in the workplace. Outside of the workplace, people can also take steps to limit their exposure to known carcinogens, such as quitting smoking, limiting sun exposure, limiting alcohol drinking, or, for those of the appropriate age, having HPV and HBV vaccination. See Risk Factors for Cancer for more information about known and suspected carcinogens.
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Oncogenes And Tumor Suppressor Genes
P53 is overexpressed in approximately 40% of breast tumors, with approximately 20% having mutations in the gene these rates are similar among African-Americans, Hispanics, and whites., , , P53 has many functions in development, DNA repair, apoptosis, cell cycle regulation, and transcription and as a tumor suppressor. Environmental genotoxins have been linked to specific mutations, or hotspots, along the P53 gene, with some being characteristic of environmental mutagens such as PAH. The resulting P53 mutational spectrum appears to vary with ethnicity and geographic distribution, which is consistent with an environmental etiology., Furthermore, as many as 10 inherited variants have been found in the P53 gene these differ by race/ethnicity and possibly are associated with a risk of breast cancer., – Potential evidence of an environmental influence on P53 inactivation includes the observation that P53 overexpression in tumors is associated with a history of smoking, which is consistent with a genotoxic effect of smoking on P53. In addition, evidence from the CBCS suggested different P53 alterations were found with smoking versus radiation exposures.
Concept 3 Environment/social Interactions
Environmental epidemiologic research generally has disregarded the fact that environmental exposures are entwined intimately with social, behavioral, and psychosocial factors. Statistical models usually include SES and race/ethnicity, but SES is measured rather crudely . Research has suggested that SES accounts for much of the racial/ethnic variability in breast cancer incidence or mortality. Both factors should be considered to obtain a more complete picture of breast cancer risk in the U.S. Other investigators believe that geographic differences in breast cancer mortality can be explained by reproductive factors and lifestyle variations across various regions in the U.S., Furthermore, it has been proposed that two socially influenced factors play an important role in breast cancer risk: tissue susceptibility brought on by reproductive factors such as early menarche and higher exposures to carcinogens.
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Environmental Determinants Of Breast Cancer
Annual Review of Public Health
Vol. 39:113-133 First published as a Review in Advance on January 12, 2018
Robert A. Hiatt1 and Julia Green Brody2
1Department of Epidemiology and Biostatistics and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94158, USA email:
2Silent Spring Institute, Newton, Massachusetts 02460, USA email:
Context 1 Environment/environment Interactions
Mammary carcinogens may interact with other exposures to increase risk above and beyond the risk associated with each individual exposure. Therefore, epidemiologic research and laboratory investigations must ascertain effects of multiple as well as single exposures, thereby advancing the understanding of joint effects. Exposures interacting with one another can have a direct and/or a modifying effect on disease risk. Combinations of exposures have not been well studied because of biologic as well as epidemiologic study design complexities. A major obstacle to the study of joint exposures is the need for large numbers of participants with complete risk factor assessments.
Some information concerning the resultant effect of multiple exposures can be gleaned from laboratory studies with the OCs, in which a combination of chemicals has been administered, usually at staggered timepoints, to assess promoter or initiator potential in animal models. The timing of tumor-promoting, tumor-inhibiting, or tumor initiating exposures is critical. Examples include dioxin , DDT, and PCBs as tumor promoters and PAH or MNU as tumor initiators., , Many in vitro studies have found effects to be additive.-
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Environmental Risk Factors And Occupational Exposure
Increasing knowledge about the carcinogenic effects of air pollution has become available. Complex components of particulate matter exhibit high carcinogenic potential through several mechanisms. In 2013, outdoor air pollution and particulate matter from outdoor air pollution were listed as carcinogenic to humans by the IARC Working Group. A heavy haze is common in northern China, which has caused great public concern. Coinciding with the largest economic growth, China also became one of the countries suffering from the worst air pollution. A report from the National Cancer Center attributed 14.4% of lung cancer deaths to PM2Â·5 air pollution in China. The GBD study estimated that the number of cancer deaths related to ambient particulate matter pollution increased by more than 300% from 1990 to 2017 . To decrease serious air pollution, legislation was passed by the government. In 2013, the National Action Plan on Air Pollution Prevention and Control was announced, which was thought to be the most influential environmental policy in China over the last decade. The Action Plan defines 10 strict measures, including controlling the production capacity of high pollution industries and promoting public transport development.
Endocrine Disrupting Chemicalspersonal Products
The evidence that endogenous hormones influence breast cancer risk raises parallel questions about the effects of synthetic chemicals that mimic or disrupt hormones, particularly estrogen signaling. Many chemicals currently in widespread use in consumer products have estrogenic activity in rodent models and in vitro. Many of these compounds are rapidly metabolized, complicating exposure assessment for epidemiological studies .
In humans, urine BPA levels in parts per billion have been documented in many studies one large study revealed that 95% of urinary samples tested contained BPA levels in parts per billion as did 94% of samples tested in a study of prepubertal 67-year-old girls in the Breast Cancer and the Environment Research Program across the United States . However, researchers are uncertain about the level and risk of exposure to BPA in humans. In one of the few epidemiologic prospective studies of the health effects of BPA in 1,151 girls between 6 and 8 years old, after two years of follow-up, the data showed no statistically significant effect on pubertal onset .
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What Is Niehs Doing
NIEHS plays a leadership role in funding and conducting studies on the ways in which environmental exposures increase breast cancer risk. This research seeks to understand the role of environmental agents, such as toxic chemicals, in the initiation and progression of cancer, as well as genetic susceptibility. Identifying and reducing contact with environmental factors linked to breast cancer presents tremendous opportunity to prevent this disease.
Sister Study The NIEHS Sister Study has recruited more than 50,000 sisters of women with breast cancer from the U.S. and Puerto Rico. This landmark observational study is looking at lifestyle and environmental exposures, as well as genetic and biological factors that may increase breast cancer risk. Important findings from this study follow.
Two Sister Study An offshoot of the Sister Study, this study focuses on breast cancer in women younger than 50, who may have different breast cancer risk factors than older women. Approximately 1,300 women with young-onset breast cancer are participating, along with their sisters from the Sister Study and their biological parents. Some results from the study include the following.
In-house NIEHS researchers have also studied how environmental exposures can interact with genetic factors to affect breast cancer risk.
Some hallmark findings from BCERP follow.
Which Environmental Factors Increase The Risk For Breast Cancer
A number of environmental exposures have been investigated in relation to breast cancer risk in humans, including the following :
Of these environmental exposures, only high doses of ionizing radiation to the chest area, particularly during puberty, have been unequivocally linked with an increased risk of breast cancer in adulthood. Because of the strong association between ionizing radiation exposure and breast cancer risk, medical diagnostic procedures are performed in such a way as to minimize exposure to the chest area, particularly during adolescence.
Women with a history of radiation exposure to the chest area should be examined and counseled regarding their risk of breast cancer on the basis of the timing and dose of the previous exposure. A patient treated for Hodgkin lymphoma with Mantel radiation that includes the breasts in the radiation field has a 5-fold higher risk of developing breast cancer. This risk increases markedly for women treated during adolescence evidence suggests that cumulative risk increases with age as a function of age of exposure and type of therapy.
Current evidence does not support a significant and reproducible link between other environmental exposures and breast cancer risk. Thus, a number of factors remain suspect but unproven.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan. 71 :7-33. . .
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