MAINZ, Germany—BioNTech Diagnostics GmbH, a subsidiary of BioNTech AG, announced the publication of study data indicating advantages of the molecular in-vitro diagnostic test kit, MammaTyper, over current methods of detection used in breast cancer subtyping. In the prospective-retrospective study, MammaTyper demonstrated precise quantitative detection of the biomarkers ERBB2 (HER2), ESR1 (ER), PGR (PR) and MKI67 (proliferation marker Ki-67).
The MammaTyper Kit is indicated for characterization of tumor tissue from female patients diagnosed with invasive breast cancer. The test—which has been validated for total RNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissue samples from resection or biopsy material—is used for molecular subtyping of breast cancer tissue into luminal A-like, luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive (non-luminal) and triple-negative (ductal) tumors (according to St Gallen classification ).
“The positive study data for MammaTyper underline our commitment to making personalized medicine broadly available for treating cancer,” said Dr. Sierk Poetting, managing director at BioNTech Diagnostics.
Poetting explained that MammaTyper enables a quantitative and reproducible determination for the mRNA expression of the four markers via RT-qPCR. He added that the test overcomes intra- and inter-laboratory variations of IHC-based assessment, and that test performance is not affected by fluctuation in tumor cell content.
“RT-qPCR technologies open up new dimensions in breast cancer diagnostics,” he said. “The technology has a series of widely acknowledged methodological advantages, and it is quantitative by nature with a wide dynamic range. More than 800 patient samples have been analyzed in retrospective clinical performance evaluation studies. There are reliable quantitative values per marker. Each marker is classified as positive or negative according to validated cut-off values.”
MammaTyper was superior to immunohistochemistry in assessment of tumor proliferation status with regard to the prognosis when measuring MKI67 (Ki-67), according to Poetting. He cited other advantages of the test: delivering prognostic information for patients’ risk of developing distant metastases and overall survival based on precise subtyping, delivering predictive information for treatment selection based on accurate subtyping and benefit for (neo)adjuvant chemotherapy and endocrine therapy, applicability in any molecular pathology with results available in one day and wider dynamic range than IHC.
MammaTyper is based on quantitative one-step RT-qPCR technology, combining reverse transcription of mRNA and subsequent quantitative PCR of the resulting cDNA. Signal detection is performed in real time by fluorescently labeled hydrolysis probes. Expression results are normalized against two reference genes. Additionally, a calibrator corrects for inter-run and inter-instrument variations. Besides quantitative and highly reproducible performance data, the test kit delivers fast and reliable results with ready-to-use assay mixes.
The kit was validated using real-time PCR instruments. It was developed and validated for use with RNA, which was extracted and purified from FFPE breast cancer tissue samples using the RNXtract RNA extraction kit, according to the manufacturer’s instructions for use. Eluates from the RNXtract kit can be directly used in the MammaTyper test. With the fast and easy-to-handle RT-qPCR protocol, quantitative relative gene expression data of the four biomarkers can be generated within one day. MammaTyper results show a high precision as well as intra- and inter-run reproducibility, according to the company.
In addition to the already-published FinHer study and technical validation study, BioNTech Diagnostics is working on a MammaTyper reproducibility study. Breast cancer samples were measured at 10 different sites in Europe, North America and Asia, and the study will probably be published by the end of the year, Poetting said. The company is also working on studies that prove that MammaTyper can predict the benefit of neoadjuvant chemotherapy. The first study is likely to be published this year.
“As to the commercial potential, the company’s aim is to establish MammaTyper as a first-line in-vitro diagnostic test for the stratification of breast cancer tumors,” Poetting concluded.