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Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients


Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles. Accordingly, exploratory biomarkers are increasingly incorporated in early clinical trials, thus demanding a new process of patient selection. Here, we describe the implementation of preemptive, multiplexed biomarker profiling linked to standard diagnostic algorithms for metastatic breast cancer patients treated at the West German Cancer Center. Profiling for experimental biomarkers was prospectively offered to patients with metastatic breast cancer who met generic clinical trial inclusion criteria. Formalin-fixed, paraffin-embedded tumor samples were retrieved and studied for potentially “actionable” biomarkers related to active clinical trials by immunohistochemistry, amplicon sequencing, and in situ hybridization. The clinical course of those “profiled” patients was closely monitored to offer trial participation whenever applicable. Here, we report results from the first 131 patients enrolled in this program. PIK3CA mutations (23 %) and amplifications (2 %), loss of PTEN expression (13 %), and FGFR1 amplifications (8 %) were detected next to established biomarkers such as estrogen (67 %) and progesterone receptor expression (52 %), and HER2 overexpression or amplification (23 %). So far 16 “profiled” patients (12 %) have been enrolled in biomarker-stratified early clinical trials. Preemptive profiling of investigational biomarkers can be integrated into the diagnostic algorithm of a large Comprehensive Cancer Center. Extensive administrative efforts are required to successfully enroll “profiled” patients with metastatic breast cancer in early clinical trials stratified by exploratory biomarkers.

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We thank all patients who participated in this program. All members of the clinical trial team of the Department of Medical Oncology and contributing staff members of the Institute of Pathology and Neuropathology, and the Department of Gynecology and Obstetrics, University Hospital Essen, are thanked. This work was supported by research grants from Novartis, an Oncology Center of Excellence grant from the Deutsche Krebshilfe to the West German Cancer Center, and by intramural research funds of the Medical Faculty of the University Duisburg-Essen (IFORES 107-10430 to M.S.).


AW: Novartis, Amgen (consulting fees), Roche (consulting fees and travel support); MW: Amgen (travel support), Roche (travel support); RK: Astrazeneca (consulting fees); BHL, MRP, UH: Novartis (employment); MS: Boehringer Ingelheim (institutional research funding, consulting fees), Novartis (institutional research funding, consulting fees); SK: Roche (travel support), Amgen, Merck Serono (consulting fees, speakers fee, and travel support)

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Correspondence to Martin Schuler.

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Welt, A., Tewes, M., Aktas, B. et al. Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients. Breast Cancer Res Treat 142, 81–88 (2013).

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  • Biomarker
  • Metastatic breast cancer
  • Mutation
  • Personalized medicine
  • Profiling