我们的目的是阐明雌激素受体 (ER) 阳性/人表皮生长因子受体 2 (HER2) 阴性的青少年和年轻人（AYA：40 岁以下）乳腺癌 (BC) 与其他年龄组相比的特征BC，考虑到与年龄相关的激素状态的影响。分析的队列分为 AYA（15-39 岁）、围绝经期（40-54 岁）、更年期（55-64 岁）和老年（65 岁）老的）。使用基因集变异分析和 xCell 算法，使用来自 ER 阳性/HER2 阴性 BC 大型公共数据库的转录组图谱（METABRIC；n = 1353，SCAN-B；n = 2381）对临床病理学和生物学特征进行分析。 AYA 中阳性/HER2 阴性亚型、病理淋巴结阳性和诺丁汉 3 级均较高（均 P < 0.001）。 AYA 患者的疾病特异性生存率和总体生存率有较差的趋势，特别是与围绝经期患者相比。雌激素反应晚期信号随着年龄的增长而降低（METABRIC 和 SCAN-B 队列中所有 P ≤ 0.001）。与其他组相比，AYA 与显着更高的 BRCA 和 DNA 修复相关（两个队列中所有 P < 0.05）。与其他基因组相比（所有 P <两个队列中均为 0.03）。有趣的是，这些特征也在 <2 cm 的肿瘤中观察到。 AYA 中 CD8+、调节性 T 辅助细胞和 M1 巨噬细胞的浸润较高，而 M2 巨噬细胞较低（两个队列中所有 P < 0.03）。最后，AYA患者中ER阳性/HER2阴性BC具有不同的基因突变特征，其中AHNAK2、GATA3、HERC2和TG在AYA中观察到的发生率较高，而KMT2C在AYA中观察到的发生率较低。与其他年龄组相比，AYA 中的 ER 阳性/HER2 阴性 BC 与其他年龄组相比，AYA 中的 ER 阳性/HER2 阴性 BC 具有高度增殖性和高免疫细胞浸润性。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

We aimed to clarify the features of adolescents and young adults (AYA: younger than 40 years old) breast cancer (BC) compared with other age groups in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC, given the effects of age-related hormonal status.The cohorts analyzed were divided into AYA (15-39 years old), perimenopausal (40-54 years old), menopausal (55-64 years old), and old (65+ years old). Clinicopathological and biological features were analyzed using gene set variation analysis and xCell algorithm using transcriptome profiles from large public databases of ER-positive/HER2-negative BC (METABRIC; n = 1353, SCAN-B; n = 2381).In the ER-positive/HER2-negative subtype, pathological lymph node positivity, and Nottingham grade 3 were higher among AYA (all P < 0.001). AYA patients had a trend toward worse disease-specific and overall survival, particularly compared with the perimenopausal group. Estrogen response late signaling decreased with age (all P ≤ 0.001 in both METABRIC and SCAN-B cohorts). AYA was associated with significantly higher BRCAness and DNA repair than the other groups (all P < 0.05 in both cohorts). AYA significantly enriched cell proliferation-related and procancerous gene sets [mTORC1, unfolded protein response, and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling] when compared with the others (all P < 0.03 in both cohorts). Interestingly, these features have also been observed in tumors <2 cm. Infiltration of CD8+, regulatory, T helper type 2 cells, and M1 macrophages was higher, while M2 macrophages were lower in AYA (all P < 0.03 in both cohorts). Finally, ER-positive/HER2-negative BC in AYA patients has different features of gene mutations, including AHNAK2, GATA3, HERC2, and TG, which were observed at a higher rate in AYA, and KMT2C, which was observed at a lower rate in AYA, compared with other age groups.ER-positive/HER2-negative BC in AYA was highly proliferative with high immune cell infiltration compared with the other age groups.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.