Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105, Amsterdam, AZ, Netherlands.
Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105, Amsterdam, AZ, Netherlands.
BMC Cancer. 2017 Nov 13;17(1):755. doi: 10.1186/s12885-017-3691-9.
To better predict the likelihood of response to chemotherapy, we have conducted a study comparing the gene expression patterns of primary tumours with their corresponding response to systemic chemotherapy in the metastatic setting.
mRNA expression profiles of breast carcinomas of patients that later developed distant metastases were analyzed using supervised and non-supervised classification techniques to identify predictors of response to chemotherapy. The top differentially expressed genes between the responders and non-responders were identified and further explored. An independent dataset which was generated to predict response to neo-adjuvant CT was utilized for the purpose of validation. Response to chemotherapy was also correlated to the clinicopathologic characteristics, molecular subtypes, metastatic behavior and survival outcomes.
Anthracycline containing regimens were the most common first line treatment (58.4%), followed by non-anthracycline/non-taxane containing (25.8%) and taxane containing (15.7%) regimens. Response was achieved in 41.6% of the patients to the first line CT and in 21.8% to second line CT. Response was not found to be significantly correlated to tumour type, grade, lymph node status, ER and PR status. Patients with HER2+ tumours showed better response to anthracycline containing therapy (p: 0.002). Response to first and second line chemotherapy did not differ among gene expression based molecular subtypes (p: 0.236 and p: 0.20). Using supervised classification, a 14 gene response classifier was identified. This 14-gene predictor could successfully predict the likelihood of better response to first and second line CT (p: <.0001 and p: 0.761, respectively) in the training set. However, the predictive value of this gene set in data of response to neoadjuvant chemotherapy could not be validated.
To our knowledge, this is the first study revealing the relation between gene expression profiles of the primary tumours and their chemotherapy responsiveness in the metastatic setting. In contrast to the findings for neoadjuvant chemotherapy treatment, there was no association of molecular subtype with response to chemotherapy in the metastatic setting. Using supervised classification, we identified a classifier of chemotherapy response; however, we could not validate this classifier using neoadjuvant response data.
Non applicable. Subjects were retrospectively registered.
为了更好地预测化疗反应的可能性，我们进行了一项研究，比较了原发性肿瘤的基因表达模式与其在转移性环境中的系统化疗反应。
使用有监督和无监督分类技术分析患者乳腺癌的 mRNA 表达谱，以确定化疗反应的预测因子。确定了 responder 和 non-responder 之间差异表达的基因，并进一步进行了探索。为了验证目的，使用了生成的预测新辅助 CT 反应的独立数据集。还将化疗反应与临床病理特征、分子亚型、转移行为和生存结果进行了相关性分析。
含蒽环类药物的方案是最常见的一线治疗方案（58.4%），其次是非蒽环类/非紫杉烷类（25.8%）和紫杉烷类（15.7%）方案。一线 CT 治疗的患者中，有 41.6%的患者有反应，二线 CT 治疗的患者中有 21.8%的患者有反应。反应与肿瘤类型、分级、淋巴结状态、ER 和 PR 状态无显著相关性。HER2+肿瘤患者对含蒽环类药物的治疗反应更好（p：0.002）。基于基因表达的分子亚型，一线和二线化疗的反应无差异（p：0.236 和 p：0.20）。使用有监督分类，确定了一个 14 基因反应分类器。该 14 基因预测因子可成功预测一线和二线 CT 治疗（p：<0.0001 和 p：0.761）的反应可能性。然而，该基因集在新辅助化疗反应数据中的预测价值无法验证。
据我们所知，这是第一项揭示原发性肿瘤基因表达谱与其在转移性环境中化疗反应之间关系的研究。与新辅助化疗治疗的发现相反，在转移性环境中，分子亚型与化疗反应无关联。使用有监督分类，我们确定了一个化疗反应分类器；然而，我们无法使用新辅助反应数据验证该分类器。
不适用。研究对象为回顾性注册。
