Sun Hengwen, Huang Wei, Ji Fei, Pan Yi, Yang Lu
Department of Radiation Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Cancer Center, Department of Breast Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Cell Dev Biol. 2022 Jul 14;10:923371. doi: 10.3389/fcell.2022.923371. eCollection 2022.
Metastases are the main cause of breast cancer-related deaths. Breast cancer has a more aggressive phenotype and less favorable prognosis in young females than in older females. In this study, we aimed to compare the metastatic patterns, survival outcomes and tumor immune microenvironment of young and non-young breast cancer patients. Patients with a diagnosis of breast cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The significance of young age (≤40 years) in the metastatic profile and prognosis of breast cancer was investigated. The transciptome expression data were acquired from The Cancer Genome Atlas (TCGA) database. And the differentially expressed genes (DEGs) and primarily enriched function pathways were identified by comparing between young and non-young breast cancer samples, and tumor immune infiltrating cell types in the tumor microenvironment were compared. A total of 281,829 female breast cancer patients were included in SEER: 18,331 young (6.5%) and 263,498 non-young (93.5%) women. The metastatic rates of bone, liver and distant lymph nodes (DLNs) in the young cohort were significantly higher than those in the non-young cohort. The most frequent two-site metastatic combination was bone and liver (0.61%) in the young cohort, whereas it was bone and lung (0.32%) in the non-young cohort. Breast cancer-specific survival (BCSS) was significantly shortened among those in the young cohort compared with those in the non-young cohort ( < 0.001). Young age was associated with significantly shorter BCSS only among patients with HR+/HER2- tumors ( < 0.001). The enriched biological pathways based on DEGs between two cohorts were related to the regulation of immune response and several metabolic processes. M2 macrophages were significantly abundant in non-young breast cancer than young breast cancer. Young and non-young breast cancer patients present with different metastatic patterns. Young age is a negative prognostic factor, particularly for HR+/HER2- breast cancer. The differences in metastatic patterns between young and non-young cohorts should be taken into account in the clinical management of metastatic breast cancer. The young breast cancer patients may gain better response to immunotherapy due to immune activated TME than non-young breast cancer.
转移是乳腺癌相关死亡的主要原因。与老年女性相比，年轻女性的乳腺癌具有更具侵袭性的表型和更差的预后。在本研究中，我们旨在比较年轻和非年轻乳腺癌患者的转移模式、生存结果和肿瘤免疫微环境。从2010年至2015年的监测、流行病学和最终结果（SEER）数据库中识别出乳腺癌患者。研究了年轻（≤40岁）在乳腺癌转移特征和预后中的意义。转录组表达数据从癌症基因组图谱（TCGA）数据库中获取。通过比较年轻和非年轻乳腺癌样本，确定差异表达基因（DEGs）和主要富集的功能途径，并比较肿瘤微环境中的肿瘤免疫浸润细胞类型。SEER共纳入281,829例女性乳腺癌患者：18,331例年轻患者（6.5%）和263,498例非年轻患者（93.5%）。年轻队列中骨、肝和远处淋巴结（DLNs）的转移率显著高于非年轻队列。年轻队列中最常见的双部位转移组合是骨和肝（0.61%），而非年轻队列中是骨和肺（0.32%）。与非年轻队列相比，年轻队列中的乳腺癌特异性生存（BCSS）显著缩短（<0.001）。仅在HR+/HER2-肿瘤患者中，年轻与显著缩短的BCSS相关（<0.001）。基于两个队列之间DEGs的富集生物途径与免疫反应调节和几个代谢过程相关。非年轻乳腺癌中的M2巨噬细胞比年轻乳腺癌中的显著丰富。年轻和非年轻乳腺癌患者表现出不同的转移模式。年轻是一个负面预后因素，特别是对于HR+/HER2-乳腺癌。在转移性乳腺癌的临床管理中应考虑年轻和非年轻队列之间转移模式的差异。由于免疫激活的肿瘤微环境，年轻乳腺癌患者可能比非年轻乳腺癌患者对免疫治疗有更好的反应。
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