Breast Cancer Risk Linked to Air Pollution Exposure

New data on estimates of historical air pollution show a potential link between exposure to fine particulate matter (PM_2.5), a known human carcinogen that contains a mixture of solid particles and liquid droplets, and greater risk of estrogen receptor–positive (ER+) breast cancer, according to a study published in Journal of the National Cancer Institute.

Composite image of crossed fingers with breast cancer ribbon | Image Credit: vectorfusionart - stock.adobe.com

Not only is breast cancer the most commonly diagnosed malignancy worldwide—among women, at least¹—but is also the most expensive cancer treated in the United States.² Known risk factors include alcohol intake, obesity, reproductive history, and use of exogenous hormones, which the present study’s authors note “are consistent with the importance of hormones in the etiology of the disease and suggest that environmental chemicals with endocrine-disrupting properties have the potential to influence breast cancer risk.”¹

However, despite an uptick in investigations of the relationship between air pollution and breast cancer development, there is but inconsistent evidence connecting PM_2.5 and the cancer. Few studies have evaluated historic exposure, instead focusing on PM_2.5 at or close to a study enrollment. The authors used nationwide data from the National Institutes of Health–AARP Diet and Health Study for patients enrolled from 1995 through 1996 (N = 196,905) from California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania, as well as Atlanta, Georgia, and Detroit, Michigan. They also estimated historical PM_2.5 concentrations for each participant’s address from 1980 to 1984, 1985 to 1989, and 1990 to 1994, or 10 to 15 years before study enrollment, “given the length of time it takes for some cancers to develop,” according to a press release on the findings.³

The investigators conducted separate investigations of ER+ and ER-negative (ER–) tumors. Overall, 15,870 cases of breast cancer were identified during a median 20.7 years of follow-up, which was through 2017.

Ninety-two percent of the incident cases of breast cancer were identified in postmenopausal women, whose mean age was 61.8 years; 89% were non-Hispanic White, and 44% were never-smokers; most lived in California (31%) or Florida (21%), and PM_2.5 concentrations were highest for women in California and Pennsylvania. Further, even though non-Hispanic Black women comprised 6% of the study cohort, they accounted for 12% of the women in the highest exposure quartile.

From 1980 through 1994, mean PM_2.5 concentrations fell from 18.70 mcg/m³ to 15.60 mcg/m³, or 17%. Still, a 10 mcg/m³ PM_2.5 increase for 1980 to 1984 was linked with an overall 8% greater breast cancer risk (HR, 1.08; 95% CI, 1.02-1.13; P = .004), a rate that was also seen is areas of higher PM_2.5 concentration in quartiles 3 and 4 vs quartiles 1 and 2). For 1985 to 1989 and 1990 to 1994, the overall risk for breast cancer was 7% (1985-1989: HR, 1.07; 95% CI, 1.02-1.13; 1990-1994: HR, 1.07; 95% CI, 1.01-1.14) greater for every 10 mcg/m³ PM_2.5 increase, but the risk was even higher in quartiles 3 and 4 vs 1 and 2 (both P = .003):

• 1985 to 1989:
  • Quartile 1: referent
  • Quartile 2: 4% (HR, 1.04; 95% CI, 0.99-1.09)
  • Quartile 3: 8% (HR, 1.08; 95% CI, 1.02-1.14)
  • Quartile 4: 8% (HR, 1.08; 95% CI, 1.03-1.15)
• 1990 to 1994:
  • Quartile 1: referent
  • Quartile 2: 6% (HR, 1.06; 95% CI, 1.01-1.11)
  • Quartile 3: 9% (HR, 1.09; 95% CI, 1.04-1.16)
  • Quartile 4: 9% (HR, 1.09; 95% CI, 1.03-1.15)

For the analysis that examined risk between ER+ and ER– disease, every 10 mcg/m³ PM_2.5 increase equated to a 10% increase in ER+ breast cancer risk only (HR, 1.10; 95% CI, 1.04-1.17). And when the authors looked at invasive tumors vs ductal carcinoma in situ (DCIS), a type of cancer contained within the milk ducts,⁴ there was no statistically significant difference in risk (8% vs 2%), but they did note that “the association for DCIS attenuated and less precise compared with invasive tumors.”

By study area, Louisiana and California had the lowest risks and North Carolina and Atlanta, the highest:

• Louisiana: 4% (HR, 1.04; 95% CI, 0.68-1.57)
• California: 6% (HR, 1.06; 95% CI, 1.00-1.13)
• Atlanta: 22% (HR, 1.22; 95% CI, 0.68-2.19)
• North Carolina: 26% (HR, 1.26; 95% CI, 0.96-1.64)

“This study included a large, geographically diverse population with more than 15,000 breast cancer cases identified, providing sufficient power to conduct stratified analyses, particularly by tumor characteristics,” the authors noted. “An additional strength of our study is the use of historical PM_2.5, which provides a more temporally relevant exposure window for the development of breast cancer with its estimated minimum latency of 15 years.”

Still, they emphasize that future work in this area should focus not only on evaluation of historic exposures, but also investigate potential region-specific associations and the chemical composition of PM_2.5 “in modifying the observed association with breast cancer,” and which may contain metals, metalloids, organic compounds, ammonium, nitrate, ozone, and sulfate.

References

1. White AJ, Fisher JA, Sweeney MR, et al. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. J Natl Cancer Inst. Published online September 11, 2023. doi:10.1093/jnci/djad170

2. Dr Kristine Slam: Value-based care in breast cancer requires collaboration. AJMC.com. September 19, 2023. Accessed September 22, 2023. https://www.ajmc.com/view/dr-kristine-slam-value-based-care-in-breast-cancer-requires-collaboration

3. High levels of particulate air pollution associated with increased breast cancer incidence. News release. National Institutes of Health. September 11, 2023. Accessed September 22, 2023. https://www.nih.gov/news-events/news-releases/high-levels-particulate-air-pollution-associated-increased-breast-cancer-incidence

4. Sun B. Ductal carcinoma in situ. Johns Hopkins Medicine. Accessed September 22, 2023. https://tinyurl.com/5ustj3h5