与老年患者相比，青少年和年轻成人乳腺癌具有独特的生物学特性，且患者预后较差。

Breast cancer in adolescents and young adults has a specific biology and poor patient outcome compared with older patients.

作者信息

Oshi M, Yamada A, Gandhi S, Wu R, Sasamoto M, Yamamoto S, Narui K, Ishikawa T, Takabe K, Endo I

机构信息

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, USA.

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

出版信息

ESMO Open. 2024 Nov;9(11):103737. doi: 10.1016/j.esmoop.2024.103737. Epub 2024 Oct 14.

DOI:10.1016/j.esmoop.2024.103737

PMID:39405895

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11525141/

Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

ER-positive/HER2-negative BC in AYA was highly proliferative with high immune cell infiltration compared with the other age groups.

摘要

背景

鉴于年龄相关激素状态的影响，我们旨在阐明雌激素受体（ER）阳性/人表皮生长因子受体2（HER2）阴性乳腺癌（BC）中青少年和青年成人（AYA：年龄小于40岁）与其他年龄组相比的特征。

方法

所分析的队列分为AYA组（15 - 39岁）、围绝经期组（40 - 54岁）、绝经组（55 - 64岁）和老年组（65岁及以上）。使用基因集变异分析和xCell算法，利用来自ER阳性/HER2阴性乳腺癌大型公共数据库（METABRIC；n = 1353，SCAN - B；n = 2381）的转录组谱分析临床病理和生物学特征。

结果

在ER阳性/HER2阴性亚型中，AYA组的病理淋巴结阳性率和诺丁汉3级更高（所有P < 0.001）。AYA患者有疾病特异性和总生存较差的趋势，特别是与围绝经期组相比。雌激素反应晚期信号随年龄下降（METABRIC和SCAN - B队列中所有P≤0.001）。与其他组相比，AYA组的BRCAness和DNA修复显著更高（两个队列中所有P < 0.05）。与其他组相比，AYA组显著富集细胞增殖相关和促癌基因集[mTORC1、未折叠蛋白反应和磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素哺乳动物靶标（PI3K/AKT/mTOR）信号通路]（两个队列中所有P < 0.03）。有趣的是，在<2 cm的肿瘤中也观察到了这些特征。AYA组中CD8、调节性、2型辅助性T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，与其他年龄组相比，AYA患者的ER阳性/HER2阴性BC具有不同的基因突变特征，包括AYA组中发生率较高的AHNAK2、GATA3、HERC2和TG，以及AYA组中发生率较低的KMT2C。