Whole exome analysis to select targeted therapies for patients with metastatic breast cancer – a feasibility study

Objective The aim of this feasibility study was to select targeted therapies according to “ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)” in patients with metastatic breast cancer (MBC).

Material and methods We established next generation sequencing (NGS) based whole exome sequencing (WES) of tumor tissue and peripheral blood for MBC patients (n= 44). Data interpretation was further supported by a browser-based Treatment Decision Support platform (MH Guide, Molecular Health, Heidelberg).

Results Due to insufficient DNA quality or failed sequencing procedure 32 patients were available for evaluation. We identified the following ESCAT LoE I or II (germline alterations are indicated with “g” otherwise they are somatic): two gBRCA1, two gBRCA2, six PIK3CA, one ESR1, three PTEN loss of function mutations, one AKT1 and two ERBB2 mutations and five samples with MSI-H. Resulting treatment options (including approved ones for the disease itself or off-label and drugs in development) were discussed in the molecular tumor board. Besides targeted therapy options MH Guide states inefficacy or safety concerns based on individual molecular characteristics. However due to the late stage of disease or irrelevance for the current treatment option none of the inefficacy or safety concerns changed our clinical therapy decision.

Conclusion Actionable genomic alterations were detected in a small but relevant proportion of patients. Nevertheless, WES is a technical challenge with sometimes long processing times and high costs. With a customized panel (38 genes) to identify relevant genomic alterations, we want to shorten time for analyses and selection of targeted therapies.

Publication History

Article published online:
21 June 2022