OCCUPATIONAL EXPOSURE TO PESTICIDES AFFECTS SYSTEMIC CYTOKINE PROFILE AND CORRELATES WITH POOR CLINICAL PROGNOSIS IN YOUNG WOMEN WITH BREAST CANCER.

Aging is one of the main risk factors for breast cancer. However, the impact of environmental risk factors, such as pesticide exposure, on the clinical outcomes of patients with breast cancer, depending on disease onset, remains unclear. This study analyzed clinicopathological data from 188 women with breast cancer, who were either occupationally or domestically exposed to pesticides, or not exposed, according to their age at disease onset (early onset ≤ 50 years and late onset > 50 years). Additionally, interleukin 4 (IL-4), interleukin 17A (IL-17A), and interleukin 12 (IL-12) levels were measured in plasma samples, and clinicopathological data were assessed. In the late-onset group, a greater frequency of low-grade tumors was detected in the exposed patients compared to the unexposed group (23.14% vs. 45.45%, p = 0.0181). A higher frequency of high-risk stratification for recurrence and death was found in early-onset patients when comparing exposed and unexposed groups (10.0% vs. 30.0%, p = 0.0488). Regarding the molecular subtypes of breast cancer, patients in the late-onset group showed a higher frequency of triple-negative tumors than unexposed women with the same disease onset (20.0% vs. 40.63%, p < 0.0001). IL-12 levels were significantly lower in exposed patients in the early-onset group compared to unexposed patients in the same group. Early-onset patients showed a principal component that positively correlated with pesticide exposure, IL-1β, IL-17A, and IL-4, while late-onset patients showed negative correlations between pesticide exposure and IL-12, IL-4, and IL-17A. These findings suggest that pesticide exposure induces an inflammaging-like state in younger women, contributing to an increased risk of developing more severe disease.