It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Lugano, Switzerland, 17 October 2023 – Women living and working in places with higher levels of fine particle air pollution are more likely to get breast cancer than those living and working in less polluted areas. Results of the first study to take account of the effects of both residential and workplace exposure to air pollution on breast cancer risk are presented at the ESMO Congress 2023 in Madrid, Spain (1).
“Our data showed a statistically significant association between long term exposure to fine particle air pollution, at home and at work, and risk of breast cancer. This contrasts with previous research which looked only at fine particle exposure where women were living, and showed small or no effects on breast cancer risk,” said Professor Béatrice Fervers, Head of Prevention Cancer Environment Department, Léon Bérard Comprehensive Cancer Centre, France.
In the study, home and workplace exposure to pollution in 2419 women with breast cancer was compared to that in 2984 women without breast cancer over the period 1990-2011. The results showed that breast cancer risk increased by 28% when exposure to fine particle (PM2.5) air pollution increased by 10 µg/m3 – approximately equivalent to the difference
inPM2.5 particle concentration typically seen in rural versus urban areas of Europe. Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particle air pollution (PM10 and nitrogen dioxide). Fervers and colleagues now plan to investigate the effects of pollution exposure during commuting to get a complete picture of effects on breast cancer risk.
Professor Charles Swanton, the Francis Crick Institute, London, UK, whose research suggesting how PM2.5 particles may trigger lung cancer in non-smokers was presented at ESMO Congress 2022 (2), stressed the importance of the new findings with breast cancer.
“These very small particles can penetrate deep into the lung and get into the bloodstream from where they are absorbed into breast and other tissues. There is already evidence that air pollutants can change the architecture of the breast (3,4). It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumour promotion possibly through inflammatory processes, similar to our observations in non-smokers with lung cancer,” he said. “It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression and progression of breast tumours,” he added.
“There is now strong epidemiological and biological evidence for the link between PM2.5 particle exposure and cancer, and there are good clinical and economic reasons for reducing pollution in order to prevent cancers,” said Professor Jean-Yves Blay, ESMO Director of Public Policy.
Following on a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particles in the air from the current 25 µg/m3 to 10 µg/m3 by 2030, ESMO urged a reduction in the PM2.5 limit still further to 5 µg/m3, in line with the World Health Organisation’s air quality guidance (5). “Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumour types, including breast cancer,” Blay added. “We have a responsibility to push for this change, not only for people in Europe but worldwide where there are big variations in the pollution landscape.” The lower limit was indeed adopted by the European Parliament’s Environment, Public Health and Food Safety Committee in June 2023.
More recently, in September 2023, the European Parliament adopted in plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for Fine Particulate Matter (PM2.5) at 5 µg/m³. This adoption opens interinstitutional negotiations between the co-legislators – European Parliament, European Commission and EU Council – to agree on the final text of the directive. (6,7)
“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” the ESMO Public Policy Director concluded.
-END-
Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO Congress 2023
Official Congress Hashtag: #ESMO23. Follow it to stay up to date and use it to take part in the conversation on X (Twitter), LinkedIn, Instagram, Facebook
Disclaimer
This press release contains information provided by the author of the highlighted abstract and reflects the content of this abstract. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.
References
1 Fervers B et al. Longterm residential and workplace exposure to air pollution and breast cancer risk: A case-control study nested in the French E3N cohort from 1990 to 2011 will be presented by Fervers B. during the Mini Oral Session on Monday, 23 October 2023, 16:30-18:00 CEST, at ESMO Congress 2023, Madrid (Bilbao Auditorium).
2 Swanton C et al. Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer: Towards molecular cancer prevention. Presented at ESMO Congress 2022, Paris, France Presidential Symposium 1, LBA1
3 Niehoff NM et al. Outdoor air pollution and terminal duct lobular involution of the normal breast. Breast Cancer Res 2020; 22,100.
4Kotake R et al. An association between mammographic breast density and fine particulate matter among postmenopausal women. Environ Sci Pollut Res Int. 2023 Feb;30(10):25953-25958.
About the European Society for Medical Oncology (ESMO) Representing more than 33,000 oncology professionals from 170 countries worldwide, ESMO is a reference for oncology education and information. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE. www.esmo.org
LONGTERM RESIDENTIAL AND WORKPLACE EXPOSURE TO AIR POLLUTION AND BREAST CANCER RISK: A CASE-CONTROL STUDY NESTED IN THE FRENCH E3N COHORT FROM 1990 TO 2011
B. Fervers1, M. Duboeuf1, A. Amadou1, T. Coudon1, L. Grassot1, E. Faure2, G. Severi3, F. Mancini3, P. Salizzoni4, J. Gulliver5, D. Praud1 [Text Wrapping Break]1Cancer And Environment Department, Centre Léon Bérard, Lyon/FRANCE, 2Exposome, Hérédité, Cancer Et Santé, Gustave Roussy, Villejuif/FRANCE, 3Exposome, Hérédité, Cancer Et Santé Inserm 1018, Gustave Roussy, Villejuif/FRANCE, 4Mécanique Des Fluides, Ecole Centrale, Ecully/FRANCE, 5Centre For Environmental Health And Sustainability, University of Leicester, Leicester/UNITED KINGDOM
Background: Air pollution, classified as carcinogenic to humans, is a major public health concern. Studies on breast cancer are scarce and remain inconsistent. We studied the association between breast cancer risk and long-term exposure to particulate matters (PM2.5, PM10) and nitrogen dioxide (NO2) estimated at the womens' residential and workplace addresses. Methods: We conducted a case-control study of 2419 cases and 2984 individually matched controls nested in the French prospective E3N cohort, over the period 1990-2011. Controls were matched to cases on department of residence, age (±1 year); date (±3 months), and menopausal status at blood collection. Annual mean PM2.5, PM10 and NO2 concentration levels were estimated using a Land Use Regression (LUR) model (resolution 50m x 50m) and were assigned to women based on their geocoded residential and workplace addresses. The mean exposure was calculated for each woman from their inclusion into the E3N cohort to their index date (date of diagnosis of cases). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression models, for a 10 µg/m3 increase in PM2.5, PM10 and NO2. Adjustment variables were selected from the literature, using a directed acyclic graph. Results: The results showed a statistically significant linear increase in breast cancer risk related to mean exposure to PM2.5 (adjusted OR 1.28; CI 1.00–1.63, for an increment of 10 µg/m3). A numerically increased risk was observed for PM10 (adjusted OR1.09; CI 0.92–1.30) and NO2 (adjusted OR 1.05; CI 0.97–1.13) for an increment of 10 µg/m3. No effect modification by menopausal status was observed (p interaction 0.99, 0.90, and 0.86 respectively for PM2.5PM10 and NO2). Analyses by hormone receptor status showed a positive but not significant association for PM2.5 for oestrogen receptor positive (ER+) breast cancer cases (adjusted OR 1.32; CI 0.97–1.79). Conclusions: To our knowledge, this study is the first to investigate breast cancer risk associated with long term air pollution exposure at both, the subjects’ residence and workplace, estimated using a very fine spatial resolution LUR model. Future studies should consider exposure during commuting.
Legal entity responsible for the study: INSERM
Funding: Foundation or academic group WITHOUT funding from a pharma, biotech, or other commercial company[Text Wrapping Break]- ARC Foundation for Cancer Research (CANCAIR201601245), ANSES, French League against Cancer, Fondation de France
Disclosure: All authors have declared no conflicts of interest.
Friday, August 11, 2023
CORRECTION: Outdoor air pollution may increase non-lung cancer risk in older adults
HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH
NEWS RELEASE
*This press release was amended on August 9, 2023. Due to a mistake in interpretation of data, the previous version of the release stated the study found that NO2 exposure is associated with a decreased risk of breast cancer. The authors have confirmed that the results showed that NO2 exposure is associated with an increased risk of breast cancer.
Key points:
A cohort study of millions of Medicare beneficiaries found that chronic exposures to PM2.5 and NO2 over a 10-year period increased the risk of developing colorectal and prostate cancers.
Even in areas with low pollution levels, researchers found substantial associations between exposures to these pollutants and the risk of developing colorectal and prostate cancers, in addition to breast and endometrial cancers.
Boston, MA—Chronic exposure to fine particulate air pollutants (PM2.5) and nitrogen dioxide (NO2) may increase non-lung cancer risk in older adults, according to a study led by Harvard T.H. Chan School of Public Health. In a cohort study of millions of Medicare beneficiaries, the researchers found that exposures to PM2.5 and NO2 over a 10-year period increased the risk of developing colorectal and prostate cancers. The researchers also found that even low levels of air pollution exposure may make people particularly susceptible to developing these cancers, in addition to breast and endometrial cancers.
“Our findings uncover the biological plausibility of air pollution as a crucial risk factor in the development of specific cancers, bringing us one step closer to understanding the impact of air pollution on human health,” said Yaguang Wei, research fellow in the Department of Environmental Health. “To ensure equitable access to clean air for all populations, we must fully define the effects of air pollution and then work towards reducing it.”
The study was published online August 1, 2023, in Environmental Epidemiology.
While air pollution has been established as a risk factor for lung cancer, and a link to breast cancer risk has been emerging, few studies have looked at its effects on prostate, colorectal, and endometrial cancer risk.
Researchers analyzed data from national Medicare beneficiaries aged 65 or older, collected from 2000 to 2016. All subjects were cancer-free for at least the initial 10 years of the study period. The researchers created separate cohorts for each type of cancer—breast, colorectal, endometrial, and prostate—with between 2.2 million and 6.5 million subjects in each cohort. Separate analyses looked at cancer risk under the impacts of air pollutants for various subgroups by factors including age, sex (for colorectal cancer only), race/ethnicity, average BMI, and socioeconomic status.
Drawing from a variety of air pollution data sources, the researchers developed a predictive map of PM2.5 and NO2 concentrations across the contiguous U.S. This was then linked to beneficiaries’ residential ZIP codes to enable the researchers to estimate individual exposures over a 10-year period.
Findings from the nationwide analysis showed that chronic PM2.5 and NO2 exposures increased the risk of developing colorectal and prostate cancers but were not associated with endometrial cancer risk. For breast cancer, NO2 exposure was associated with an increased risk, while the association for PM2.5 was inconclusive. The researchers suggested that the mixed associations may be due to variations in the chemical composition of PM2.5, which is a complex mixture of solid and liquid particles.
When the analysis was restricted to regions where air pollution levels were significantly below national standards and the composition of PM2.5 remained fairly stable, their effect on breast cancer risk was more pronounced. Stronger associations between exposures to both pollutants and endometrial cancer risk were also found at lower pollution levels.
The researchers noted that even communities with seemingly clean air were not immune to cancer risk. They found substantial associations between exposure to the two pollutants and the risks of all four cancers even at pollution levels below newly updated World Health Organization guidelines (which are lower than current U.S. standards).
“The key message here is that U.S. air pollution standards are inadequate in protecting public health,” said senior author Joel Schwartz, professor of environmental epidemiology. “The Environmental Protection Agency recently proposed stricter standards for PM2.5, but their proposal doesn’t go far enough in regulating this pollutant. Current NO2 standards are also woefully inadequate. Unless all of these standards become much, much stricter, air pollution will continue to result in thousands of unnecessary cases of multiple cancers each year.”
Other Harvard Chan School authors include Edgar Castro, Cristina Su Liu, Xinye Qiu, James Healy, and Bryan Vu.
Funding for the study came from the National Institutes of Health grants R01ES032418 and P30ES000002.
“Additive effects of ten-year exposures to PM2.5 and NO2 and primary cancer incidence in American older adults,” Yaguang Wei, Mahdieh Danesh Yazdi, Tszshan Ma, Edgar Castro, Cristina Su Liu, Xinye Qiu, James Healy, Bryan N. Vu, Cuicui Wang, Liuhua Shi, Joel Schwartz, Environmental Epidemiology, online August 1, 2023, doi: 10.1097/EE9.0000000000000265
Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people’s lives—not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America’s oldest professional training program in public health.
In what has turned out to be a delicate balancing act, the group is advising that while too much time in the sun raises the risk of skin cancer, avoiding it entirely can lead to a deficiency in vitamin D -- and that may elevate the risk of other types of cancers and diseases.
Cancer research is another form of social hysteria fueled by speculation, and lack of empirical data, by the medical pharmaceutical establishment.
Cancer is a direct result of the industrial revolution, it is the 'social disease' of capitalism. Of course a little bit of sushine never hurt anyone. Even if the Ozone layer is being depleted. Another result of industrial development.
We ban sunshine and cigarettes because it's easier than banning capitalism.
The University of Pittsburgh has created a center—considered the first of its kind anywhere—that will identify environmental causes of cancer. The center’s first director is more than ready to do battle against the disease. In fact, battles are her specialty.
Now as director of the new Center for Environmental Oncology, a collaborative venture between the Graduate School of Public Health and the University of Pittsburgh Cancer Institute, Davis will be fighting to find environmental causes of cancer. The center is the only one of its kind within a cancer institute, says Bernard Goldstein, professor and retiring GSPH dean.
The first project is a collaboration between the center and the University’s Center for Minority Health that will investigate why more young Black women have breast cancer than their White counterparts. They will examine whether beauty products for African American women contribute to increased occurrences of breast cancer. Environment isn’t limited to forests, rivers, lakes, fields, and sky. It is what we eat, what we use, and what we wear. Beauty products that target African American women often contain estrogen. This affects women in a few ways. For instance, these products might induce early menstruation, and researchers believe that women who menstruate earlier are more likely to get breast cancer. And it’s commonly believed that higher levels of estrogen contribute to increased risks of breast cancer. If African American women are using products that increase the level of estrogen in their bodies, they may be at higher risk. Bad Air a 'Genetic Risk'
In my 1972-74 studies, the male death rate from lung cancer in the most heavily polluted residential zone was 65/100,000, which was 2.83 times higher than the national average of 23/100,000 (2), compared with a 2.42 times higher rate reported in a 1988 study of the same zone involving a correction for age which reduced the ratio to 1.99, along with an additional correction for smoking which further decreased the ratio to 1.40 (5). In terms of my own experience, I suspect that the correction(s) for smoking might be excessive, because the lung cancer victims which I studied had not smoked as many cigarettes as did their "white collar" colleagues. Nevertheless, the main point to remember is that even a suspected over-correction of the raw data revealed a significant difference in lung cancer deaths between the heavily polluted zone and other areas, even when based on "guestimates" calculated 14 years later.
In a recent study of urban air pollution, a Utah county with a steel mill was compared with a county without a steel mill. The result was that 38% of respiratory cancer deaths could be attributed to the air pollution emanating from the mill.
Lung cancer among steelworkers in Ontario. In internal comparisons within the steel companies, increased lung cancer risk was observed among foundry, coke oven, and pouring pit workers. Retrospective hygiene assessment suggested that the increased risk of lung cancer among steel pourers might be related to the use of tar-based mold coating agents or to exposure to mineral fibers.
Male Breast Cancer Men who work in steel mills, blast furnaces, rolling mills, or other environments of intense heat have a slightly increased incidence of breast cancer...
Residents in Indiana’s heavily industrialized areas - particularly Lake County and Indianapolis - face an elevated risk of developing cancer from breathing air pollution, according to a new federal analysis.
The study released by the U.S. Environmental Protection Agency is the agency’s most ambitious look to date at cancer risks from breathing chemicals.
In its National Air Toxics Assessment, the EPA studied 133 chemicals emitted in 1999 by businesses and traffic. It outlines lifetime cancer risks in states, counties and census tracts.
Particles linked to climate change also promote cancerous changes in airway cells
Cells with EGFR and KRAS gene mutations can turn cancerous when exposed to air pollutants
Late-breaking data pave way to new approaches to lung cancer prevention and treatment
Paris, France, 10 September 2022 - A new mechanism has been identified through which very small pollutant particles in the air may trigger lung cancer in people who have never smoked, paving the way to new prevention approaches and development of therapies, according to late-breaking data [to be] reported at the ESMO Congress 2022 by scientists of the Francis Crick Institute and University College London, funded by Cancer Research UK (1). The particles, which are typically found in vehicle exhaust and smoke from fossil fuels, are associated with non-small cell lung cancer (NSCLC) risk, accounting for over 250,000 lung cancer deaths globally per year (2,3).
“The same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health via an important and previously overlooked cancer-causing mechanism in lung cells. The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and these new data link the importance of addressing climate health to improving human health,” said Charles Swanton, the Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, who will present the research results at the ESMO 2022 Presidential Symposium on Saturday, 10 September.
The new findings are based on human and laboratory research on mutations in a gene called EGFR which are seen in about half of people with lung cancer who have never smoked. In a study of nearly half a million people living in England, South Korea and Taiwan, exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometres (μm) in diameter was linked to increased risk of NSCLC with EGFR mutations.
In the laboratory studies, the Francis Crick Institute scientists showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells which had mutations in EGFR and in another gene linked to lung cancer called KRAS, driving them towards a cancer stem cell like state. They also found that air pollution drives the influx of macrophages which release the inflammatory mediator, interleukin-1β, driving the expansion of cells with the EGFR mutations in response to exposure to PM2.5, and that blockade of interleukin-1β inhibited lung cancer initiation. These findings were consistent with data from a previous large clinical trial showing a dose dependent reduction in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab (4).
In a final series of experiments, the Francis Crick team used state-of-the-art, ultradeep mutational profiling of small samples of normal lung tissue and found EGFR and KRAS driver mutations in 18% and 33% of normal lung samples, respectively.
“We found that driver mutations in EGFR and KRAS genes, commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of ageing. In our research, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harbouring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” said Swanton.
Commenting on the results, Tony Mok, Chinese University of Hong Kong, not involved in the study, said: “This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for pre-cancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1β inhibitors. We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find non-smokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative.”
Like Swanton, he stresses the importance of reducing air pollution to lower the risk of lung diseases, including cancer. “We have known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues – for both environmental and health reasons,” Mok concluded.
-END-
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Notes to Editors Please make sure to use the official name of the meeting in your reports: ESMO Congress 2022 Official Congress Hashtag: #ESMO22
Disclaimer This press release contains information provided by the author of the highlighted abstract and reflects the content of this abstract. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.
References
1 LBA1 ‘Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer in never smokers’ will be presented by Charles Swanton during Presidential Symposium 1 on Saturday, 10 September, 16:30 to 18:00 CEST in Paris Auditorium. Annals of Oncology, Volume 33 Supplement 7, September 2022
2 Liu X, Mubarik S, Wang S. Lung Cancer Death Attributable to Long-Term Ambient Particulate Matter (PM2.5) Exposure in East Asian Countries During 1990–2019. Frontiers in Medicine 2021 Oct 15;8:742076
3 Turner MC, Andersen ZJ, Baccarelli A et al. Outdoor Air Pollution and Cancer: An Overview of the Current Evidence and Public Health Recommendations. CA: Cancer J Clin 2020; 70: 460-479
4 Ridker PM, MacFadyen JG, Thuren T et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 2017 Oct 21; 390 (10105): 1833-1842
ESMO is the leading professional organisation for medical oncology. With 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. Drawing on more than 45 years of experience, ESMO serves its members and the oncology community by providing networking and professional growth opportunities: oncologists can engage in projects, committees and working groups aiming to promote science and foster improvements in the oncology practice. With training, resources and tools, oncologists are enabled to stay up to date with the latest scientific advances and continue to deliver the best possible care to cancer patients. By representing and advocating for the oncology community at the highest political levels, ESMO ensures that the needs of both patients and doctors are properly taken care of. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE. www.esmo.org
The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases. An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King’s College London. The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe. www.crick.ac.uk
Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research, influence and information. Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years. Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK wants to accelerate progress and see 3 in 4 people surviving their cancer by 2034. Cancer Research UK supports research into the prevention and treatment of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer Research UK is working towards a world where people can live longer, better lives, free from the fear of cancer. www.cancerresearchuk.org or +44(0) 300 123 1022
LBA1 - Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer: towards molecular cancer prevention
C. Swanton1, W. Hill2, E. Lim3, C. Lee4, C.E. Weeden5, M. Augustine6, K. Chen7, F.-C. Kuan8, F. Marongiu9, F. Rodrigues10, H. Cha11, T. Jacks12, M. Luchtenborg13, I. Malanchi14, J. Downward15, C. Carlsten16, A. Hackshaw17, K.R. Litchfield18, J. DeGregori19, M. Jamal-Hanjani20
1Translational Cancer Therapeutics Department, Francis Crick Institute, London/United Kingdom, 2Cancer Evolution And Genome Instability Laboratory, Francis Crick Institute, London/United Kingdom, 3Cancer Evolution And Genome Instability Laboratory, The Francis Crick Institute, London/United Kingdom, 4Cegi, Francis Crick Institute, London/United Kingdom, 51 Midland Rd, The Francis Crick Institute, London/United Kingdom, 6Tumour Immunogenomics And Immunosurveillance, UCL - University College London, London/United Kingdom, 7Thoracic Surgery, Peking University People’s Hospital, Beijing/China, 8Hematology Oncology, Chang Gung Medical Foundation - Chiayi Chang Gung Memorial Hospital, Puzi City/Taiwan, 9Department Of Biochemistry & Molecular Genetics, UCHealth Cancer Care - Anschutz Medical Campus - University of Colorado Cancer Center, Aurora/United States of America, 10Tumour-host Interaction Laboratory, The Francis Crick Institute, London/United Kingdom, 11Division Of Hematology-oncology, Samsung Medical Center (SMC) - Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of, 12The Jacks Lab, Koch Institute For Integrative Cancer Research at MIT, Cambridge/United States of America, 13National Cancer Registration And Analysis Service, Public Health England, London/United Kingdom, 14Tumour Host Interaction Lab, Francis Crick Institute, London/United Kingdom, 15Oncogene Biology Laboratory, The Francis Crick Institute, London/United Kingdom, 16Centre For Lung Health, UBC - The University of British Columbia, Vancouver/Canada, 17Clinical Trials, Cancer Research UK & University College London Cancer Trials Centre, London/United Kingdom, 18Tumour Immunogenomics And Immunosurveillance, UCL Cancer Institute - UCL - London's Global University, London/United Kingdom, 19Biochemistry And Molecular Genetics, UCHealth Cancer Care - Anschutz Medical Campus - University of Colorado Cancer Center, Aurora/United States of America, 20Medical Oncology Dept., UCL Cancer Institute - Paul O'Gorman Building, London/United Kingdom
Background: A mechanistic basis for non-small cell lung cancer (NSCLC) initiation in never smokers, a disease with a high frequency of EGFR mutations (EGFRm), is unknown. The air pollutant, particulate matter (PM), is known to be associated with the risk of NSCLC, however a direct cause and mechanism remain elusive.
Methods: We analysed 463,679 individuals to address the associations of increasing 2.5um PM (PM2.5) concentrations with cancer risk. We performed ultra-deep profiling of 247 normal lung tissue samples, analysed normal lung tissue from humans and mice following exposures to PM, and investigated the consequences of PM on tumour promotion in mouse lung cancer models.
Results: Increasing PM2.5 levels were associated with increased risk of EGFRm NSCLC in England, S.Korea and Taiwan and with increased risk of mesothelioma (HR=1.19), lung (HR=1.16), anal (HR=1.23), small intestine (HR=1.30), GBM (HR=1.19), lip, oral cavity and pharynx (HR: 1.15) and laryngeal carcinomas (HR=1.26) in UK Biobank; HR for each 1ug/m3 PM2.5 increment. 18-33% of normal lung tissue samples harbour driver mutations in EGFR and KRAS in the absence of malignancy. PM promotes a macrophage response and a progenitor-like state in lung epithelium harbouring mutant EGFR. Consistent with PM promoting NSCLC in at-risk epithelium harbouring driver mutations, PM increased tumour burden in three EGFR or KRAS driven lung cancer models in a dose-dependent manner. Finally, we uncover an actionable inflammatory axis driven by IL1B in response to PM, with anti-IL1B therapy preventing PM-induced mouse tumour formation, consistent with reductions in human lung cancer incidence with anti-IL1B therapy.
Conclusions: These results shed light on the aetiology of EGFRm lung cancer, particularly in never-smokers, and suggest that oncogenic mutations may be necessary but insufficient for tumour formation. These data reveal a mechanistic basis for PM driven lung cancer in the absence of classical carcinogen-driven mutagenesis, reminiscent of models of tumour initiation and promotion proposed 70 years ago, providing evidence to limit air pollution and opportunities for molecular targeted cancer prevention.
Clinical trial identification: TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx) (TRACERx) (NCT01888601) The PEACE (Posthumous Evaluation of Advanced Cancer Environment) Study (PEACE) (NCT03004755) Biomarkers and Dysplastic Respiratory Epithelium (NCT00900419)
Legal entity responsible for the study: Francis Crick Institute and UCL Hospitals NHS Trust
Funding: Foundation or academic group WITHOUT funding from a pharma, biotech, or other commercial company - This work has been supported by the Mark Foundation ASPIRE I Award (Grant 21-029-ASP), Lung Cancer Research Foundation Grant on Disparities in Lung Cancer, Advanced Grant (PROTEUS, Grant Agreement no. 835297), CRUK EDD (EDDPMA-Nov21100034), and Rosetrees Out-of-round Award (OoR2020100009). E.L.L. receives funding from NovoNordisk Foundation (ID 16584), The Mark Foundation (Grant 21-029-ASP) and has been supported by Rosetrees. W.H is funded by an ERC Advanced Grant (PROTEUS, Grant Agreement no. 835297), CRUK EDD (EDDPMA-Nov21100034), The Mark Foundation (Grant 21-029-ASP) and has been supported by Rosetrees. K.C. is supported by Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences (2021RU002), National Natural Science Foundation of China (No.82072566) and Peking University People's Hospital Research and Development Funds (RS2019-01). T.K. receives grant support from JSPS Overseas Research Fellowships Program (202060447). S.H.L is supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A2C3006535), the National Cancer Center Grant (NCC1911269-3), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HR20C0025). N.M. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (Grant Number 211179/Z/18/Z) and also receives funding from Cancer Research UK, Rosetrees and the NIHR BRC at University College London Hospitals and the CRUK University College London Experimental Cancer Medicine Centre. J.D., M.G., Y.E.M. D.T.M. and R.L.K receive funding from American Association for Cancer Research/Johnson&Johnson (18-90-52-DEGR), and J.D. is supported by the Courtenay C. and Lucy Patten Davis Endowed Chair in Lung Cancer Research. M.G., Y.E.M. D.T.M. and R.L.K. were supported by National Cancer Institute (NCI) RO1 CA219893. E.J.E. was supported by NCI Ruth L. Kirschstein National Research Service Award T32-CA190216. The work at the University of Colorado was also supported by NCI Cancer Center Support Grant P30CA046934. M.J.-H. has received funding from Cancer Research UK, National Institute for Health Research, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Centre. C.S. is Royal Society Napier Research Professor. He is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169). C.S. is funded by Cancer Research UK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK Lung Cancer Centre of Excellence, the Rosetrees Trust, Butterfield and Stoneygate Trusts, NovoNordisk Foundation (ID16584), Royal Society Research Professorships Enhancement Award (RP/EA/180007), the NIHR BRC at University College London Hospitals, the CRUK-UCL Centre, Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF). This research is supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. C.S. also receives funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013) Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (835297) and Chromavision from the European Union’s Horizon 2020 research and innovation programme (665233). This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (grant no. FC001112), the UK Medical Research Council (grant no. FC001112), and the Wellcome Trust (grant no. FC001112) and the European Research Council (grant no. ERC CoG-H2020-725492).
Disclosure:C. Swanton: Financial Interests, Personal, Invited Speaker, Activity took place in 2016.: Pfizer; Financial Interests, Personal, Invited Speaker, October 26th 2020: Novartis; Financial Interests, Personal, Invited Speaker: Roche/Ventana; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker, Activity took place in 2016.: Celgene; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Illumina; Financial Interests, Personal, Advisory Board, AdBoard - November 12th, 2020: Amgen; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Sarah Canon Research Institute; Financial Interests, Personal, Advisory Board, Joined October 2020. Also have stock options: Bicycle Therapeutics; Financial Interests, Personal, Advisory Board: Medicxi; Financial Interests, Personal, Invited Speaker: GlaxoSmithKline; Financial Interests, Personal, Advisory Board, Member of the Science Management Committee. Also have stock options: GRAIL; Financial Interests, Personal, Other, Consultancy agreement: Roche Innovation Centre Shanghai; Financial Interests, Personal, Full or part-time Employment, Chief Clinician since October 2017: Cancer Research UK; Financial Interests, Personal, Ownership Interest, Co-Founder of Achilles Therapeutics. Also, have stock options in this company.: Achilles Therapeutics; Financial Interests, Personal, Stocks/Shares, Stocks owned until June 2021: GRAIL; Financial Interests, Personal, Stocks/Shares, Stocks owned until June 2021: Apogen Biotechnologies; Financial Interests, Personal, Stocks/Shares: Epic Biosciences; Financial Interests, Personal, Stocks/Shares: Bicycle Therapeutics; Financial Interests, Institutional, Research Grant, Funded RUBICON grant - October 2018 - April 2021.: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Collaboration in minimal residual disease sequencing technologies.: Archer Dx Inc; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Invited Speaker, Chief Investigator for the MeRmaiD1 clinical trial and chair of the steering committee.: AstraZeneca; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Research Grants from 2015-2019.: Roche-Ventana; Financial Interests, Personal, Other, Co-chief investigator: NHS-Galleri Clinical Trial; Non-Financial Interests, , Principal Investigator, Chief Investigator for MeRmaiD1 clinical trial: AstraZeneca; Non-Financial Interests, , Invited Speaker, From 2019: AACR; Non-Financial Interests, , Other, Board of Directors: AACR; Non-Financial Interests, , Advisory Role, EACR Advisory Council member: EACR. T. Jacks: Financial Interests, Personal, Member of the Board of Directors: Amgen; Financial Interests, Personal, Member of the Board of Directors: Thermo Fisher Scientific; Financial Interests, Personal, Advisory Board, co-Founder: Dragonfly Therapeutics; Financial Interests, Personal, Other, co-Founder: T2 Biosystems; Financial Interests, Personal, Advisory Board: SQZ Biotech; Financial Interests, Personal, Advisory Board: Skyhawk Therapeutics; Financial Interests, Personal, Leadership Role: Break Through Cancer; Financial Interests, Institutional, Funding: Johnson & Johnson. J. Downward: Financial Interests, Personal, Other, consultant: AstraZeneca; Financial Interests, Personal, Other, consultant: Bayer; Financial Interests, Personal, Other, consultant: Jubilant; Financial Interests, Personal, Other, consultant: Theras; Financial Interests, Personal, Other, consultant: Vividion; Financial Interests, Personal, Other, consultant: Novartis; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Revolution Medicines; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim. K.R. Litchfield: Financial Interests, Personal, Invited Speaker: Roche Tissue Diagnostics; Financial Interests, Personal, Other, Consulting work: Monopteros Therapeutics; Financial Interests, Institutional, Research Grant: Ono/LifeArc; Financial Interests, Institutional, Research Grant, Research funding: Genesis Therapeutics; Non-Financial Interests, Institutional, Proprietary Information, Collaboration on data analysis: Bms. M. Jamal-Hanjani: Financial Interests, Personal, Invited Speaker, Invited speaker honorarium: Oslo Cancer Cluster; Financial Interests, Personal, Invited Speaker, Invited speaker honorarium: Astex Pharmaceutical; Non-Financial Interests, , Advisory Role, Scientific Advisory Board and Steering Committee member: Achilles Therapeutics; Other, , Other, I am named as co-inventor on patent PCT/US2017/028013 relating to methods for lung cancer detection.: Patent. All other authors have declared no conflicts of interest.
Late-breaking results presented at the ESMO Congress 2022 elucidate the link between air pollution and lung cancer
ESMO partners with EONS to launch the Cancer Prevention across Europe (PrEvCan) campaign
Study confirms accuracy of multi-cancer early detection blood testing, paving the way for a new era in cancer screening
Paris, France, 9 September 2022 – Sustainability will be at the heart of many discussions at the ESMO Congress 2022, as illustrated by the new results and initiatives spanning cancer prevention, early detection and treatment that were announced today during the opening press conference to the annual meeting of the international oncology community taking place 9-13 September in Paris, France.
“By definition, sustainability is about being able to maintain important, high-quality processes over time. In oncology, seeing the rise in cancer cases, we need to ask ourselves how we can make sure the essential process of caring for patients can be maintained,” said ESMO President Prof. Solange Peters. “Sustainability encompasses the notion of avoiding degradation, meaning that we also have to look at maintaining the quality – which, in cancer, includes the availability of and access to anticancer drugs. It also includes quality of life, which is still dependent on the environment, and as ESMO we need to start looking at the environmental sustainability of everything we do.”
Underscoring the multifaceted nature of sustainability as a societal goal, late-breaking results to be presented at the ESMO Congress 2022 offer a deeper understanding of the long-established link between air pollution and non-small cell lung cancer (NSCLC) arising in people who have never smoked, and make clear the link between climate change and human health. “Pollution has a known association with lung cancer, but we didn’t know if and how it directly causes the disease,” said study author and ESMO 2022 Scientific Co-Chair Prof. Charles Swanton, the Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, explaining the background to this work. (1)
The research, based on human and laboratory studies, showed for a population of nearly half a million people living in England, South Korea and Taiwan that exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometres (μm) in diameter was linked to increased risk of NSCLC with mutations in the EGFR gene, which are known to be present in about half of people with lung cancer who have never smoked. In laboratory mouse models, the same pollutant particles (PM2.5) were seen to directly cause lung cancer by acting through lung tissue inflammation, driving the release of a molecule known as interleukin-1β that causes epithelial cells to transdifferentiate into cancer stem-like cells. In the presence of mutations in EGFR and in another gene linked to lung cancer called KRAS, these cells can then bloom into a tumour.
“These mutations can be found in over half of normal lung tissue biopsies and are a natural process of ageing. They are necessary, but not sufficient to drive cancer: it is in combination with pollution that the cancer stem cells can expand and initiate a tumour. This begins to explain how environmental carcinogens that don’t induce DNA mutations can drive cancer,” said Swanton, deriving from this discovery a public health mandate to lower the levels of these pollutants, which are produced by the combustion of fossil fuels. “We have to achieve a 50% reduction in greenhouse gas emissions by 2030, and by doing so we will naturally reduce levels of PM2.5. We can all play a part here: we need to cycle more, walk more. It’s worth bearing in mind that PM2.5 cause 8 million deaths a year, not just due to cancer but also to other diseases like cardiovascular disease, strokes, dementia – that is more than the deaths caused by tobacco globally.”
In light of the fact that his research confirmed the blockade of interleukin-1β could inhibit lung cancer initiation by blocking the pollution-induced transformation of airway cells into cancer stem cells, Swanton also suggested that targeting interleukin-1β should be further explored in the future as a potential new approach to cancer prevention.
The findings come in a context where the global incidence of respiratory cancers is on the rise, with annual new cases expected to jump by about 70% over the next two decades. In Europe alone, similar trends observed for other malignancies could result in an increase in overall cancer mortality, from 2 million annual deaths in 2020, to as many as 3 million by 2040. (2) As up to half of all cancers are thought to be preventable, prevention is considered by the World Health Organisation to be the most cost-effective, and thus the most sustainable, long-term strategy for cancer control.
“The ESMO Vision 2025, made very clear that if we want to succeed in tackling cancer, we need to develop a clear plan for primary and secondary prevention, continue to offer the optimal care for cancers that cannot be prevented and adequately support cancer survivorship. Focusing on only one of these areas and neglecting the others would lead to failure,” said ESMO Director of Public Policy Dr. Rosa Giuliani.
In line with the Society’s commitment to promoting research-based cancer prevention, the ESMO representatives joined European Oncology Nursing Society (EONS) Executive Board member Dr. Lena Sharp, Regional Cancer Centre, Stockholm, Sweden, in announcing the launch today of the Cancer Prevention across Europe Campaign (PrEvCan).
Led by EONS with ESMO as key partner alongside other international organisations, the campaign will over a one-year period dedicate each month to promoting and explaining the scientific evidence for each one of the 12 recommendations of the European Code Against Cancer (ECAC) to prevent the disease, starting in October with smoking as one of the most important cancer risk factors.
“What is new here is that it is the cancer care workforce leading the way,” said Sharp, the PrEvCan project leader. “We are the ones who meet patients and their families, so we could intervene on a daily basis supporting and advising people to adopt healthier lifestyles to reduce the risk of new cancers but also to reduce negative effects on the current disease.”
The campaign will target the general public, including the most vulnerable groups who can be difficult to reach with health promotion and lifestyle advice, but equally healthcare professionals, who according to Sharp can also take a more prominent role in supporting vaccination and screening programmes.
The ESMO President added: “We thought for a while that prevention should be in the hands of family doctors, but then we started to learn that preventing the disease must be at least partly in the hands of the specialists of a specific disease, in order to convince people about its importance. Particularly after COVID, a certain degree of suspicion can happen in medicine. You need to make sure that everything you propose has a basis – and one of these bases for cancer prevention is the burden of cancer, what it represents not only in terms of lost years of life but also in terms of the sustainability of our societies and healthcare systems.” Peters further highlighted that oncologists should view prevention as an integral part of oncology care, also because the science of prevention still requires more data.
For cancers that are not currently avoidable, screening and early detection has the potential to both maximise individuals’ chances of survival, and alleviate the burden on health systems by reducing the proportion of patients with advanced disease who require costly, chronic therapies and care.
A study to be presented at this year’s Congress could lead to a major paradigm shift in this field, having confirmed the feasibility of multi-cancer early detection (MCED) blood testing as a method of screening for up to 50 different cancer types simultaneously. (3)
“This is one of the very first studies where the detection of cancer DNA in the blood has allowed us to detect cancer at an early stage,” said ESMO 2022 Scientific Co-Chair Prof. Fabrice André, Institute Gustave Roussy, Villejuif, France. “If this test works, in the future, it will be good news for patients, but most cancer centres are not equipped to scale up surgeries for hundreds more patients with, say, early-stage pancreatic cancer. With this landmark study comes a need for a wake-up call for hospitals to see what will happen in 10 years and start now to train fellows and change their infrastructures accordingly.”
Highlighting the time and patience required to turn promising research results into meaningful innovation for patients, Swanton observed: “ESMO 2022 is a celebration of the collaboration between basic scientists and healthcare professionals to advance care for our patients. Some of the breakthroughs that will be discussed over the next four days have come from biological studies of worms, yeast, bacteria and plants – but they took 30 or 40 years of painstaking science from the bench to the bedside. We need our funders to recognise that and to sustain investment in discovery research to generate the medicines of the future.”
Among other highly anticipated results to be presented at the ESMO Congress 2022 , André drew attention to several examples of novel approaches which could soon become a reality in the clinic: from the phase III trial of gamma secretase inhibitor (GSI) nirogacestat, a first-in-class drug targeting a new molecular alteration in a rare category of cancers known as desmoid tumours, through a landmark trial of cell therapy using tumour-infiltrating lymphocytes (TILs) to improve the outcomes of patients with advanced melanoma, all the way to several late-phase trials of immunotherapy, including for non-small cell lunger cancer patients not eligible to standard platinum chemotherapy. André welcomed the presence of studies for underrepresented patient populations in the Congress’s scientific programme, concluding: “We cannot exclude patients from clinical trials.”
In closing, ESMO 2022 Press Officer Dr. Antonio Passaro called for a wide and wise dissemination of the data to be presented: “We have here a community of about 25,000 people, with more than 1,900 abstracts and 76 LBAs that will be presented in the coming days. We need to pass these messages to all of our colleagues and the public in order to dramatically improve the future of our patients, which risks being worse than it is today considering current cancer incidence trends.”
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Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO Congress 2022
3 Abstract 903O ‘A prospective study of a multi-cancer early detection blood test’ will be presented by Deb Schrag during the proffered paper
session “Basic science and translational research” on Sunday, 11 September, 16:30 to 18:00 CEST in Orléans Auditorium. Annals of Oncology,
Volume 33 Supplement 7, September 2022
4 The ESMO ANMS 2.0 survey about access to cancer medicines will be discussed during the educational session “The Universal Health Coverage (UHC) dilemma: Can we afford to pay for what we want?” on Saturday, 10 September, 8:30 to 10:00 CEST in Marseille Auditorium.
ESMO is the leading professional organisation for medical oncology. With 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE. www.esmo.org
