Oshi Masanori, Tokumaru Yoshihisa, Angarita Fernando A, Yan Li, Matsuyama Ryusei, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Cancers (Basel). 2020 Nov 28;12(12):3557. doi: 10.3390/cancers12123557.
Endocrine therapy is the gold-standard treatment for ER-positive/HER2-negative breast cancer. Although its clear benefit, patient compliance is poor (50-80%) due to its long administration period and adverse effects. Therefore, a predictive biomarker that can predict whether endocrine therapy is truly beneficial may improve patient compliance. In this study, we use estrogen response early gene sets of gene set enrichment assay algorithm as the score. We hypothesize that the score could predict the response to endocrine therapy and survival of breast cancer patients. A total of 6549 breast cancer from multiple patient cohorts were analyzed. The score was highest in ER-positive/HER2-negative compared to the other subtypes. Earlier AJCC stage, as well as lower Nottingham pathological grade, were associated with a high score. Low score tumors enriched only allograft rejection gene set, and was significantly infiltrated with immune cells, and high cytolytic activity score. A low score was significantly associated with a worse response to endocrine therapy and worse survival in both primary and metastatic breast cancer patients. The hazard ratio was double that of expression. In conclusion, the estrogen response early score predicts response to endocrine therapy and is associated with survival in primary and metastatic breast cancer.
内分泌治疗是雌激素受体（ER）阳性/人表皮生长因子受体2（HER2）阴性乳腺癌的金标准治疗方法。尽管其益处明显，但由于给药周期长和不良反应，患者依从性较差（50%-80%）。因此，一种能够预测内分泌治疗是否真正有益的预测性生物标志物可能会提高患者的依从性。在本研究中，我们使用基因集富集分析算法的雌激素反应早期基因集作为评分。我们假设该评分可以预测乳腺癌患者对内分泌治疗的反应和生存情况。对来自多个患者队列的6549例乳腺癌进行了分析。与其他亚型相比，ER阳性/HER2阴性患者的评分最高。美国癌症联合委员会（AJCC）分期越早以及诺丁汉病理分级越低，评分越高。低评分肿瘤仅富集同种异体移植排斥基因集，并且有明显的免疫细胞浸润和高细胞溶解活性评分。低评分与原发性和转移性乳腺癌患者对内分泌治疗的反应较差以及生存情况较差显著相关。风险比是表达的两倍。总之，雌激素反应早期评分可预测对内分泌治疗的反应，并与原发性和转移性乳腺癌的生存情况相关。
