Association between outdoor ambient benzene and invasive breast cancer incidence: The Multiethnic Cohort Study

Background: Benzene is classified as a Group 1 carcinogen in humans. A major pathway of benzene exposure is through the inhalation of ambient air contaminated by emissions from motor vehicle exhaust, gas stations, industries, tobacco smoke, and other consumer products. Past studies on benzene and breast cancer based on job titles or occupational history have yielded mixed results and the role of ambient benzene and breast cancer risk has been sparsely studied. Within the California component of the Multiethnic Cohort study, we examined the association between outdoor exposure to benzene and breast cancer risk among four major U.S. racial/ethnic groups―African Americans, Latinos, Japanese Americans, and Whites. Methods: Outdoor ambient benzene exposure was estimated from U.S. EPA measurements from air monitoring stations that were within 15 km of residences of 57,589 female MEC participants, largely from Los Angeles County, from time of recruitment (1993-1996) through study end date (12/31/2010). Cox proportional hazards models were used to examine the associations between time-varying benzene exposure and invasive breast cancer risk (cases=2,388), adjusting for age, race/ethnicity, education, smoking pack-years, family history of breast cancer, body mass index, physical activity, parity and age at first live birth, age at menarche, menopausal status, use of hormone therapy, alcohol consumption, intake of total calories, and neighborhood (block group) socioeconomic status. Stratified analyses were conducted by race/ethnicity, smoking history, and hormone receptor status. Results: Outdoor ambient benzene exposure (average median level from 1993-2010 was 0.94 ppb) was associated with an increased risk of breast cancer (per 1 ppb hazard ratio [HR]=1.40, 95% confidence interval [CI]: 1.24-1.58). This positive association was observed across all racial/ethnic groups; HR ranged from 1.23 to 1.67 (p values were <0.001 in African Americans, Japanese Americans, and Whites). Analysis by smoking status at baseline showed significant increased risk among former smokers (HR=1.53, 95% CI:1.22-1.91) and never smokers (HR=1.33, 95% CI: 1.12-1.58) but this risk did not reach statistical significance among current smokers (HR=1.27, 95% CI: 0.91-1.79) (P_{heterogeneity}=0.56). A larger effect estimate of benzene was observed for hormone receptor negative (HR=1.66; 95% CI: 1.18-2.33) than for hormone receptor positive (HR=1.28, 95% CI: 1.10-1.50) breast cancer (P_{heterogeneity}=0.02). Conclusions: Benzene exposure adversely impacted the risk of breast cancer across all racial/ethnic groups but appeared to be more prominent for hormone receptor negative breast cancer after adjusting for covariates mentioned above. Additional large population-based studies with breast cancer subtypes are needed to further determine benzene9s role in breast cancer development. Citation Format: Ugonna Ihenacho, Jun Wu, Chiu-Chen Tseng, Juan Yang, Scott Fruin, Timothy Larson, Salma Shariff-Marco, Loic Le Marchand, Daniel Stram, Beate Ritz, Iona Cheng, Anna H. Wu. Association between outdoor ambient benzene and invasive breast cancer incidence: The Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-170.