Abstract

Abstract Background: The occurrence of breast cancer in young women (BCYW), i.e., under 40 years old (<40 years), is increasing, and tumors in this group often exhibit different biology and prognosis compared to those in older counterparts. Aim and Study Design: This study aimed to access the peripheral immune cell populations in metastatic BCYW at diagnosis and compare them with older (≥40) metastatic breast cancer (BC) patients. Blood samples were collected when the metastatic disease was diagnosed and before treatment began. Materials and Methods: A total of 90 patients were included, with a median age of 52.5 years at baseline (27–88 years). Among them, 17 patients were under 40 years old, and 73 were 40 years old or older. We isolated peripheral blood mononuclear cells using Histopaque-1077 Hybri-Max to access immune cells by flow cytometry. For comparisons between two groups, the Mann-Whitney-Wilcoxon test was used, and Dunn’s test was used for comparisons between more than two groups. Results: The presence of metastatic BCYW was characterized by a lower proportion of regulatory T-cells (Treg) and central memory (CM) CD8+ T-cells, as well as a higher proportion of total effector T-cells (Teff). In young patients with widespread metastasis (plurimetastatic), there was a higher proportion of Teff cells, Vδ2+ T-cells, and effector Vδ1+ T-cells, with fewer Treg cells. Conversely, older plurimetastatic patients had more Treg cells and fewer effector T-cells. Furthermore, young oligometastatic patients had a lower proportion of CM CD8+ T-cells. Conclusions: BCYW presents a distinct immunologic profile with higher effector cell activity and lower levels of regulatory and memory cells, regardless of metastatic burden and menopausal status. This finding suggests that targeting immune pathways may offer new therapeutic strategies to improve outcomes for young women with BC, potentially leading to more personalized and effective treatments.