Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Medicon Village, 223 81, Lund, Sweden.
Department of Oncology, Växjö Central Hospital, Växjö, Sweden.
Breast Cancer Res Treat. 2019 Jun;175(2):305-316. doi: 10.1007/s10549-019-05138-7. Epub 2019 Feb 22.
According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC).
Biomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets.
AIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3-20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1-7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not.
AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.
根据 2017 年圣加仑替代定义的内在亚型，Ki67、孕激素受体（PR）和诺丁汉组织学分级（NHG）用于对雌激素受体（ER）阳性/HER2 阴性乳腺癌进行预后分类，分为 luminal A 或 luminal B 样。本研究的目的是研究是否有其他与内分泌信号通路相关的生物标志物，如乳腺癌扩增物 1（AIB1）、雄激素受体（AR）和 G 蛋白偶联雌激素受体（GPER），可以在一组 ER 阳性/HER 阴性浸润性小叶癌（ILC）中提供补充的预后信息。
对 224 例患者的组织微阵列进行免疫组织化学分析。主要终点是乳腺癌死亡率（BCM），分析时随访 10 年和 25 年（FU）。此外，还分析了三个公开的 ILC 数据集的这些生物标志物的基因表达数据的预后价值。
AIB1（高 vs. 低）在多变量分析中与 BCM 相关（调整年龄、肿瘤大小、淋巴结状态、NHG、Ki67、luminal 样分类和辅助全身治疗），随访 10 年时 HR 为 6.8（95%CI 2.3-20，P=0.001），随访 25 年时 HR 为 3.0（95%CI 1.1-7.8，P=0.03）。通过将基因表达数据与独立的公开 ILC 数据集的结果相关联，可以证实 AIB1 具有预后作用的证据。AR 和 GPER 与 10 年或 25 年 FU 时的 BCM 均无相关性（P>0.33）。此外，Ki67 和 NHG 在 10 年和 25 年 FU 时均为 BCM 的预后因素，而 PR 则不是。
AIB1 是 ER 阳性/HER2 阴性 ILC 的一种新的潜在预后生物标志物。
