Growing evidence of the Role of Air Pollution in Breast Cancer Development

Growing Evidence for the Role of Air Pollution in Breast
Cancer Development
Alexandra J. White, PhD1
DOI https://doi.org/10.1200/JCO-24-01987
Breast cancer remains the most commonly diagnosed cancer among women in the
United States1 and worldwide.2,3 Although survival after a breast cancer diagnosis is high (91% at
5 years after diagnosis),4 there are wide-ranging consequences, including treatment side effects, adverse mental health impacts,5 and high financial toxicity.6 Epidemiologic research has
identified a number of breast cancer risk factors, including reproductive history (eg, age at
menarche, parity, breastfeeding)4 as well as alcohol use,4 postmenopausal obesity,4 and cigarette smoking.7 Despite the large number of identified risk factors and the proliferation of
interventions to reduce some of these exposures, incidence rates have increased for many
groups.8 The lack of progress may be attributed in part to the fact that most of these risk factors
are not easily modifiable and only modestly contribute to incidence (ie, relative risk
estimates <2.0).4 There is a critical need to identify and quantify the impact of new modifiable breast cancer risk factors, such as environmental chemicals.9 However, demonstrating a causal relationship between environmental exposures and breast cancer has been challenging because of difficulties in accurately measuring these ubiquitous exposures, particularly at the low levels at which they may still be harmful.10 Outdoor air pollution is a particularly promising candidate risk factor given that it contains carcinogenic chemicals11 and endocrine disruptors,12 which may be particularly relevant for breast cancer given its relationship to hormonal factors. Outdoor air pollution was classified as a Group 1 carcinogen on the basis of epidemiologic evidence for fine particulate matter (PM2.5) and lung cancer and mechanistic and experimental studies,11 and there has been limited investigation into how air pollution is related to other cancer sites.13 Although outdoor air pollution is not amenable to individual-level modifications, policy-driven interventions have been effective in reducing exposure.14,15 Early epidemiologic studies of air pollution and breast cancer supported an association between breast cancer incidence and traffic-related emissions, such as nitrogen dioxide (NO2), but studies for PM2.5 remained inconclusive.16 This lack of consistency may be reflective of the challenges in exposure assessment and lack of statistical power to detect modest effect estimates. Routine PM2.5 monitoring by the Environmental Protection Agency started in 1999.17,18 Some studies relied on air pollution exposure models that estimated past exposure on the basis of more recent monitored concentrations.19 In addition, many studies focused on exposure estimated for a single residence (eg, enrollment address20-22). These approaches do not allow for the consideration of changes in air pollution concentrations across the different spaces people travel or over time. This may result in substantial exposure misclassification, particularly from residential mobility.23,24 Indeed, while some early studies of PM2.5 did not find an association,25-27 others that did find an association had CIs that were too wide to draw firm conclusions.21,28 Consequently, two 2021 meta-analyses concluded that there was no evidence of an association.29,30 However, the tide recently began to turn; large, well-designed studies with sufficient sample size and statistical power to detect a modest association began to accumulate support for a positive relationship.31-35 In the article that accompanies this editorial, Wu et al36 present new findings on the role of air pollutants in the risk of breast cancer in a racially and ethnically diverse cohort of over 58,000 Californian women in the Multiethnic Cohort (MEC) Study. This article is an update to a previous analysis, which observed positive but not statistically significant findings.28 With >700 new
cases accrued in an additional follow-up of 8 years since their previous analysis, Wu et al36 used
updated air pollution exposure models to estimate residential air pollution concentrations of
ACCOMPANYING CONTENT
Article, 10.1200/
JCO.24.00418
Accepted October 4, 2024
Published October 28, 2024
J Clin Oncol 00:1-4
Published by American Society
of Clinical Oncology
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particulate matter and gaseous pollutants (NO2, NOx, and
ozone, among others) from 1993 to 2018. Over an average
follow-up period of 19 years, over 3,500 incident breast
cancer cases were diagnosed.
The key findings of this study include a statistically significant 28% (95% CI, 1.09 to 1.51) higher incidence of breast
cancer for a 10 mg/m3 increase in PM2.5. The hazard ratio (HR)
was slightly stronger for hormone receptor–negative
compared with hormone receptor–positive tumors (HR,
1.26 v 1.17), albeit with overlapping CIs. For the trafficrelated pollutants NO2 and NOx, 8%-10% higher hazard
ratios were observed and, although not statistically significant, are similar to previous studies.29
A key strength of this cohort is that this study population is
racially, ethnically, and socioeconomically diverse, with over
50% of the cohort having less than a high school education.
Most previous analyses in US cohorts, with the exception of
the Black Women’s Health Study,20 have been composed of
predominately White women and those of a higher socioeconomic status.21,25,35 The MEC study population almost
exclusively lives in urban areas, which experience higher
concentrations of air pollution. In addition, racial and ethnic
minoritized individuals are more likely to experience higher
air pollution because of historic redlining37 and the inequitable
placement of industrial facilities38 and highways.39 Although
there was little evidence of racial or socioeconomic disparities
in this study—with the strongest estimates for the PM2.5
association observed in White women—it is noteworthy that
the average concentration of pollutants in this cohort is high
across all groups, reflecting the urbanicity of this population.
For example, average PM2.5 levels at baseline were 23.6 mg/m3
.
By contrast, the average PM2.5 level was 12.0 mg/m3 in the
Nurses Health Study40 and 15.6 mg/m3 in the National Institute
of Health (NIH)-AARP (formally known as the American
Association of Retired Persons) Diet and Health Study cohort
for a similar time frame (1990-1994).35 In 2023, the mean
PM2.5 concentration in the United States was 8.5 mg/m3
.
41
The inclusion of a meta-analysis of previous cohort studies on
the topic is an important contribution. This meta-analysis
comes at a critical time, as the previous meta-analyses29,30 did
not include the more recent, large, and well-conducted
studies that did observe an effect. In the meta-analysis of
cohort studies by Wu et al36 including the new findings from
MEC, they estimated a summary hazard ratio of 1.05 (95% CI,
1.00 to 1.10) per 10 mg/m3 of PM2.5. This 10 mg/m3 increase in
PM2.5 reflects a large shift in exposure, which is equivalent to
going from the 10th to the 90th percentile in the United States
in 2000; for 2023, the difference between the 90th and 10th
percentile is about 4 mg/m3
.
41 While it is challenging to
compare the magnitude of this association with that of other
breast cancer risk factors (eg, reproductive history, alcohol
intake) because of the very different scales, this is similar to
the estimates between PM2.5 exposure and lung cancer risk
(9% increase)42 and incident stroke (13% increase).43 While
the size of these effect estimates is modest, because of the
ubiquitous nature of air pollution, the public health burden
may be substantial.29 Furthermore, it is entirely plausible
that these estimates may be biased toward the null because
of the limitations of air pollution exposure assessment.44,45
Although epidemiologic studies have improved with better
exposure models and with incorporating exposure estimates for multiple residences, these studies have largely not
considered exposure away from the home (eg, commuting
or at the workplace) or during the hypothesized most
susceptible windows such as puberty and pregnancy,46 when
exposures might have a stronger effect.47 Ascertaining
exposure during these windows has been challenging because of the timeframe for air pollution monitoring, but
future studies will be better poised to estimate air pollutant
exposure during these critical periods.
Importantly, the studies on outdoor air pollution and breast
cancer incidence have overwhelmingly been conducted in
study populations in the United States, Canada, and
Europe.29,31,32,34,35 Rapid industrialization and urbanization,
particularly in middle- and low-income countries, has
resulted in higher air pollution levels, with annual average
PM2.5 concentrations vastly above the WHO guideline of
5 mg/m3
.
48-50 Breast cancer is the most common cancer diagnosed among women in China and India.3 Yet, epidemiologic research in these areas with the highest ambient air
pollution is limited.33,51,52 In the one prospective cohort study
conducted in China, in >80,000 women living in Beijing who
experienced exceptionally high PM2.5 (5-year average: 78.15
mg/m3
), positive linear associations were observed with total
PM2.5, with variation in the association by individual PM2.5
constituents.51 Future studies are needed in China and other
countries with high ambient air pollution using data from
large study populations with strong exposure assessment to
better characterize the global impact of PM2.5 on breast
cancer.
THE TAKEAWAY
In the article that accompanies this editorial, Wu et al36 observed that residential exposure to fine particulate matter was
associated with higher breast cancer incidence using prospective data from over 58,000 California women in the Multiethnic Cohort Study. These findings, together with a meta-analysis of findings from cohort studies included in the
manuscript, highlight the importance of environmental contributors to breast cancer risk.
2 | Published by American Society of Clinical Oncology
White
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Despite the declines in US air pollution exposure since
the Clean Air Act, PM2.5 concentrations are no longer
decreasing.15,41 With climate-driven increases in wildfire
frequency and intensity, it is estimated that PM2.5 concentrations will increase approximately 10% in the next
30 years.53 With this increase in concentrations will likely
come a change in PM2.5 composition—wildfire-related PM2.5
composition includes higher concentrations of chemicals
such as metals and polycyclic aromatic hydrocarbons,54,55
which have been associated with endocrine disruption56 and
a higher risk of breast cancer.57 Future research needs to
consider how PM2.5 composition, which varies geographically,
may affect observed associations with breast cancer21,22 to
identify the most important PM2.5 sources to target for interventions to reduce exposure.
As demonstrated by the meta-analysis in the study by Wu et al,36
the epidemiologic literature is converging on PM2.5 as a risk
factor for breast cancer. These findings support additional
policy-level interventions to reduce outdoor air pollution concentrations, particularly given the projected increases in PM2.5
because of wildfires. Increased awareness of the relationship
between air pollution and breast cancer for both physicians and
patients could facilitate more routine capturing of information
related to a patient’s residential histories. Although exposure to
outdoor air pollution is largely not directly modifiable or
treatable, patients’ comprehensive residence information can be
used to estimate air pollutant exposure concentrations58 and
other residence-based environmental exposures. In doing so, we
can pave the way for a better understanding of the environmental contributors to breast cancer etiology.
AFFILIATION
1
Epidemiology Branch, National Institute of Environmental Health
Sciences, National Institute of Health, Durham, NC
CORRESPONDING AUTHOR
Alexandra J. White, PhD; e-mail: [email protected].
DISCLAIMER
This is a US Government work. There are no restrictions on its use.
SUPPORT
Supported in part by the National Institute of Environmental Health
Sciences Intramural Program (Z01 ES-103332).
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
Disclosures provided by the author are available with this article at DOI
https://doi.org/10.1200/JCO-24-01987.
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