Air pollution fueling a spike in breast cancer risk

By Hugo Francisco de SouzaSep 13 2023

In a recent study published in the Journal of the National Cancer Institute, researchers used a nationwide large United States (US) cohort spatiotemporal model to investigate the associations between air pollution exposure estimates and breast cancer risk in women. Their results suggest that exposure to PM_2.5 was correlated with an increased risk of breast cancer. An increase of as little as 10 µg/m³ was found to be sufficient to increase breast cancer risk by 8% in US women.

Study: Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. Image Credit: VanderWolf Images / Shutterstock

Particulate matter and breast cancer

Breast cancer is the most common cancer among women globally, with prevalence estimated at more than 7.8 million patients worldwide. Breast cancer occurs in every country of the world in women at any age after puberty but with increasing rates in later life. It is characterized by lumps on the breasts, changes in shapes or texture of the breasts or nipples, or bloody discharges from the nipples.

Breast cancer is a heterogeneous disease with multiple known risk factors, including women’s reproductive history, alcohol consumption, obesity, and the use of exogenous hormones. These risk factors have been observed to be consistent with the disease etiology, suggesting that breast cancer might be modulated or caused by environmental pollutants with endocrine-disrupting properties. Airborne particulate matter smaller than 2.5 µm in diameter (PM_2.5) has been classified as a known human carcinogen by the International Agency for Research on Cancer. Evidence from this is derived primarily from lung cancer research, with the role of PM_2.5 in breast cancer remaining contentious.

Fine particulate matter is a complex cocktail of numerous pollutants, including metals (nickel, sodium), metalloids (silicon), ammonium, ozone, organic compounds, nitrates, and sulfates. While recent research has identified the role of nitrogen dioxide (NO₂) as an airborne carcinogen, research on fine particulate matter remains rare and contrasting. Some studies find no association between PM_2.5 and breast cancer risk, while others find a positive correlation between these entities. Of the few studies that do exist, the methodology focuses on present or short-term exposure, ignores geographical variability in air quality, and remains devoid of tumor subtype analyses.

Given the prevalence of breast cancer and the gradually increasing global rate of disease incidence, research identifying the causal factors of the disease is essential, as these could help inform policy interventions to curb the spread of the potentially fatal condition.

About the study

The present study aimed to investigate the association between historic PM_2.5 concentrations and breast cancer risk in a large, geographically diverse US-based cohort. As a secondary objective, the study aimed to identify associations between air pollution and specific cancer subtypes, as determined by their estrogen receptor profiles.

Sample data included in this study was obtained from participants enrolled in the National Institutes of Health (NIH)-AARP cohort. Questionnaire data on anthropometric and demographic characteristics were initially obtained in 1995-96, with follow-up data obtained from 2004 through to study completion (December 31, 2017). Data on cancer and place of residence were collected from hospital medical records, State cancer registries, and the US Postal Service (USPS) National Change of Address database.

After excluding proxy respondents, male enrolees, and self-reported cancer at the study commencement, the final sample cohort comprised 196,905 adult female participants from six States (Florida, California, New Jersey, Louisiana, North Carolina, and Pennsylvania) and two metropolitan areas (Detroit, MI, and Atlanta, GA). Data on temporally informative PM_2.5 measurement from the Interagency Monitoring of Protected Visual Environment (IMPROVE) network (1999-2010) and the US Environmental Protection Agency’s Federal Reference Method (FRM) network (1999-2010) were used to build and validate this study’s spatiotemporal PM_2.5 prediction model.

Over 300 geographic predictors in tandem with spatial smoothening were used to estimate temporal trends in PM_2.5 concentrations for periods between 1980-2010, wherein recorded data, either from the above-mentioned agencies or from the Clean Air Status and Trends Network (1987-2010) and Weather Bureau Army Navy network visual ranges (1980-2010) were unavailable. For the purpose of statistical analysis, researchers divided historical exposure (before study commencement) into three 5-year periods – 1980-1984, 1985-1989, and 1990-1994. Spearman correlations were used along with calculated frequencies and proportions (categorical variables) and mean and standard deviations (continuous variables).

Cancers were classified via estrogen receptor status into ‘ER+’ and ‘ER- ‘. The extent of the tumor was used to further classify cancers as ‘invasive’ or ‘Ductal carcinoma in situ (DCIS).’ The Cox proportional hazards regression model was used to elucidate the association between PM2.5 and breast cancer. All models employed were adjusted for age, race and ethnicity, smoking status, body mass index (BMI), educational level, and geographical catchment area. Since previous research suggests that minority communities live in areas exposed to higher levels of air pollution, race and ethnicity were considered confounders. In contrast, other sociodemographic and anthropometric characteristics were considered covariates.

Model heterogeneity was computed using stratified analysis, and model robustness was evaluated using sensitivity analyses.

Study findings

Over the median 20.7 years of follow-up, this study found 15,870 breast cancer-positive cases, 8% of the study cohort. Of these, 14,621 patients were postmenopausal women (92%) whose mean age was 61.8 years. Most (89%) of these women belong to the White ethnicity, 30% were found to have studied beyond college, and most belonged to Florida (21%) or California (32%). Confounder analyses revealed that, despite only comprising 6% of the cohort, Black women were most often geographically located in areas with the highest PM_2.5 exposure.

In a promising revelation, PM_2.5 levels were found to decrease by approximately 17% between 1980 and 1994. However, the effects of PM_2.5 exposure were found to have long-term effects, with results suggesting that a 10 µg/m³ increase in fine particulate matter exposure during the 1980-84 period increased the risk of breast cancer by 8%. Stratified analyses suggest that PM_2.5 increases the risk of ER+ cancers but does not affect ER-cancer risk. No statistically meaningful association could be made between air pollution and DCIS or invasive cancers.

One of the main limitations of this study was the study cohort – the NIH-AARP study enrolls participants who have retired, the youngest of whom are age 50. This study, therefore, cannot capture the effects of PM_2.5 exposure in young women whose bodies might respond differently to air pollution of varying concentrations. Nevertheless, it presents the first concrete evidence of PM_2.5 exposure having a direct impact on the risk of developing ER+ breast cancer in the future, highlighting the need for policies (at the administrative level) and behavioral changes (individual level; e.g., face masks) to protect against these almost invisible, yet deadly pollutants.

Conclusion

In the present study, researchers used demographic and anthropometric data from 196,905 adult female participants to investigate their risk of developing cancer between 1980 and 2010. Spatiotemporal modeling of historic air pollution levels revealed that an increase of 10 µg/m³ of PM_2.5 concentrations was sufficient to increase breast cancer (ER+) risk by 8%.

“Future work should emphasize evaluation of historic exposures and consider region-specific associations and the potential contribution of PM_2.5 chemical constituency in modifying the observed association with breast cancer.”