晚期乳腺癌的免疫基因表达和对化疗的反应。

Immune gene expression and response to chemotherapy in advanced breast cancer.

机构信息

Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden.

Department of Radiology and Nuclear Medicine, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden.

出版信息

Br J Cancer. 2018 Feb 20;118(4):480-488. doi: 10.1038/bjc.2017.446. Epub 2018 Jan 25.

BACKGROUND

Transcriptomic profiles have shown promise as predictors of response to neoadjuvant chemotherapy in breast cancer (BC). This study aimed to explore their predictive value in the advanced BC (ABC) setting.

METHODS

In a Phase 3 trial of first-line chemotherapy in ABC, a fine needle aspiration biopsy (FNAB) was obtained at baseline. Intrinsic molecular subtypes and gene modules related to immune response, proliferation, oestrogen receptor (ER) signalling and recurring genetic alterations were analysed for association with objective response to chemotherapy. Gene-set enrichment analysis (GSEA) of responders vs non-responders was performed independently. Lymphocytes were enumerated in FNAB smears and the absolute abundance of immune cell types was calculated using the Microenvironment Cell Populations counter method.

RESULTS

Gene expression data were available for 109 patients. Objective response to chemotherapy was statistically significantly associated with an immune module score (odds ratio (OR)=1.62; 95% confidence interval (CI), 1.03-2.64; P=0.04). Subgroup analysis showed that this association was restricted to patients with ER-positive or luminal tumours (OR=3.54; 95%, 1.43-10.86; P=0.012 and P for interaction=0.04). Gene-set enrichment analysis confirmed that in these subgroups, immune-related gene sets were enriched in responders.

CONCLUSIONS

Immune-related transcriptional signatures may predict response to chemotherapy in ER-positive and luminal ABC.

背景

转录组谱已显示出作为乳腺癌（BC）新辅助化疗反应预测因子的潜力。本研究旨在探讨其在晚期 BC（ABC）环境中的预测价值。

方法

在 ABC 一线化疗的 3 期试验中，在基线时获得细针穿刺活检（FNAB）。分析固有分子亚型和与免疫反应、增殖、雌激素受体（ER）信号传导和复发性遗传改变相关的基因模块，以关联对化疗的客观反应。对应答者与无应答者进行独立的基因集富集分析（GSEA）。在 FNAB 涂片上计数淋巴细胞，并使用微环境细胞群体计数器方法计算免疫细胞类型的绝对丰度。

结果

109 例患者的基因表达数据可用。化疗的客观反应与免疫模块评分有统计学显著关联（优势比（OR）=1.62；95%置信区间（CI），1.03-2.64；P=0.04）。亚组分析表明，这种关联仅限于 ER 阳性或 luminal 肿瘤患者（OR=3.54；95%CI，1.43-10.86；P=0.012，交互作用 P=0.04）。基因集富集分析证实，在这些亚组中，应答者中富集了与免疫相关的基因集。