Breast cancer in Adolescent & Young Adult (AYA) has a specific biology and poor patient outcome compared to older patients

Abstract

Abstract Background We aimed to clarify the features of adolescents and young adults (AYA: younger than 40yo) breast cancer (BC) compared with other age groups in ER-positive/HER2-negative BC, given the effects of age-related hormonal status. Methods The cohorts analyzed were divided into: AYA (15-39yo), Perimenopausal (40-54yo), Menopausal (55-64yo), and Old (65 + yo). Clinicopathological and biological features were analyzed using gene set variation analysis and the xCell algorithm using transcriptome profiles from large public databases of ER-positive/HER2-negative BC (METABRIC; n = 1,353, SCAN-B; n = 2,381). Results Tumors were larger and more advanced among the AYA and Old age groups than among the other groups. Pathological lymph node positivity and Nottingham grade 3 were higher among AYA. AYA was significantly associated with triple-negative BC and higher HER2-positivity. AYA had poorer disease-specific and overall survival particularly compared to perimenopausal group. In the ER-positive/HER2-negative subtype, estrogen response late signaling decreased with age. AYA was associated with significantly higher BRCAness and DNA repair than the other groups. AYA significantly enriched cell proliferation-related and pro-cancerous gene sets (MTORC1, unfolded protein response, and PI3K/AKT/MTOR signaling) when compared to the others. Interestingly, these features have also been observed in small tumors. Infiltration of CD8+, regulatory, and helper type 2 T cells, and M1 macrophages was higher, while M2 macrophages were lower in AYA. Finally, ER-positive/HER2-negative BC in AYA patients has different features of gene mutations compared to other age groups. Conclusions ER-positive/HER2-negative BC in AYA was highly proliferative with high immune cell infiltration compared to other generations.