Department of General Surgery, Qingdao Municipal Hospital (East), Qingdao, China.
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Breast Cancer Res Treat. 2018 Dec;172(3):689-702. doi: 10.1007/s10549-018-4950-4. Epub 2018 Sep 17.
Although age is a recognized independent prognostic risk factor, its relative importance among molecular subtypes of Breast cancer (BCA) is not well documented. The aim of this study was to evaluate the prognostic role of age at diagnosis among different immunohistochemical subtypes of BCA.
We conducted a retrospective study of women with invasive BCA undergoing surgery at the Johns Hopkins Hospital, excluding patients presenting with stage IV breast cancer. Patients were stratified into three age groups: ≤ 40, 41-60, and > 60 years, and multivariable analysis was performed using Cox regression. We also identified differentially expressed genes (DEG) between age groups among BCA subtypes in the public TCGA dataset. Finally, we identified key driver genes within the DEGs using a weighted gene co-expression network analysis.
Luminal A breast cancer patients had significantly lower 5 year disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the ≤ 40 year age group compared to the 41-60 year age group, while the other molecular subtypes showed no significant association of DFS or DMFS with age. Age was a stronger outcome predictor than tumor grade or proliferative index in Luminal A BCA patients, but not other subtypes. BCA TCGA gene expression data were divided into two groups (≤ 40 years, > 40 years). We identified 374 DEGs in the Luminal A BCA subset, which were enriched in seven pathways and two modules of co-expressed genes. No age group-specific DEGs were identified in non-Luminal A subtypes.
Age at diagnosis may be an important prognostic factor in Luminal A BCA.
尽管年龄是公认的独立预后危险因素，但在乳腺癌（BCA）的分子亚型中，其相对重要性尚未得到充分记录。本研究旨在评估诊断时年龄在不同免疫组织化学 BCA 亚型中的预后作用。
我们对在约翰霍普金斯医院接受手术的浸润性 BCA 女性进行了回顾性研究，排除了患有 IV 期乳腺癌的患者。患者分为三个年龄组：≤40 岁、41-60 岁和>60 岁，并使用 Cox 回归进行多变量分析。我们还在公共 TCGA 数据集的 BCA 亚型中鉴定了不同年龄组之间的差异表达基因（DEG）。最后，我们使用加权基因共表达网络分析在 DEG 中鉴定关键驱动基因。
Luminal A 乳腺癌患者在≤40 岁年龄组的 5 年无病生存率（DFS）和远处无转移生存率（DMFS）明显低于 41-60 岁年龄组，而其他分子亚型的 DFS 或 DMFS 与年龄无明显相关性。年龄是 Luminal A BCA 患者比肿瘤分级或增殖指数更强的预后预测因素，但在其他亚型中并非如此。BCA TCGA 基因表达数据分为两组（≤40 岁，>40 岁）。我们在 Luminal A BCA 亚组中鉴定出 374 个 DEG，这些基因在七个途径和两个共表达基因模块中富集。在非 Luminal A 亚型中未鉴定出年龄组特异性 DEG。
诊断时的年龄可能是 Luminal A BCA 的一个重要预后因素。
