Abstract ES11-3: Novel approaches for selection of and monitoring treatment
Authors: Denkert C 
Published: February 2018

With the introduction of new therapeutic options in advanced and metastatic breast cancer, there is a growing demand for new biomarkers to guide treatment decisions.

There are several differences compared to early breast cancer that have to be addressed to define the clinical use of precision medicine in advanced and metastatic breast cancer.

The current challenges include the limited availability of tissue in metastatic disease, the problems of spatial heterogeneity in large advanced tumors, as well as differences between different metastatic sites. In addition, it has been shown that in metastatic and recurrent tumors, new molecular alterations develop under therapeutic pressure, for example mutations in the ESR1 receptor.

The current guidelines suggest that the basic characterization of the tumor using the standard markers of hormone receptors and HER2 should be repeated in the metastatic setting, if possible. Differences between primary and recurrent tumors have been observed in a comparably small percentage of tumors, nevertheless these differences may open new therapeutic options. Therefore, rebiopsies should be performed, if possible, these biopsies are also highly relevant for the evaluation of new therapy strategies in clinical trials.

Another relevant challenge is the heterogeneity of the tumor cells at different metastatic sites, these different metastases originate from different cell clones and have therefore a different molecular background, in particular in those tumors that have a high intratumoral molecular diversity. Considering this heterogeneity between different metastases as well as technical difficulties in the conduction of biopsies, new technologies have been established to monitor tumor biomarkers on a systemic level. This includes the evaluation of circulating tumor cells as well as the evaluation of cell-free circulating DNA (cfDNA) in so called liquid-biopsies. Several translational studies shown that sequencing of cfDNA is suitable to detect tumor mutations that can be used distinguish different groups of tumors with different response rates, for example to PIK3CA inhibitors. Relevant mutations include ESR1 and PIK3CA, which are relevant for therapy resistance in breast cancer and can be measured by NGS-sequencing. In breast cancer, these investigations are currently not part of the clinical routine. In lung cancer, the analysis of T790M EGFR mutations in liquid biopies are routinely used to guide therapeutic decisions in recurrent disease, which shows that the introduction into the clinical setting is feasible. The presentation will discuss the advantages and limitations of the different methods, and give examples for biomarker strategies for different therapies including endocrine therapy, immune therapy and targeted therapy.

Citation Format: Denkert C. Novel approaches for selection of and monitoring treatment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES11-3.