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Study confirms analytical precision of MammaTyper® in molecular breast cancer typing

Mainz, Germany, July 12, 2016:  BioNTech Diagnostics GmbH announces the publication of new study data which confirms the high analytical performance of the in vitro diagnostic test kit MammaTyper® (CE labeled IVD) in breast cancer subtyping [1]. MammaTyper® allows a precise quantitative determination of the mRNA expression of the biomarkers ERBB2 (HER2), ESR1 (ER), PGR (PR) and MKI67 (proliferation marker Ki-67), and a molecular subtyping of the tumor tissue according to the St. Gallen guidelines. Thus, MammaTyper® provides an optimized tumor stratification, which is, among other things, a basis for the selection of an effective therapy for each patient [2]. According to Professor Arndt Hartmann of Erlangen University Hospital: “The results of the current study show that MammaTyper® delivers reproducible quantitative values for the four biomarkers recommended in the St. Gallen guidelines – independently of individual laboratory conditions.” Dr. Sierk Poetting, Managing Director at BioNTech Diagnostics GmbH, commented: “Once again the MammaTyper® test kit has been proven as an unambiguous technical advance in breast cancer subtyping.” The results of a prospective-retrospective clinical study published in May 2016 demonstrated MammaTyper®´s essential advantages  compared to established methods of detecting biomarkers with regard to disease free survival and overall survival [2].

There has been recent criticism of the established IHC and FISH/CISH methods to determine biomarkers, particularly, with respect to the reproducibility and comparability of the values for the marker Ki-67 [3-7]. MammaTyper® technology is based on the molecular determination of the mRNA expression of the four biomarkers from formalin-fixed and paraffin-embedded tumor tissue (FFPE), using the RT-qPCR method (reverse transcription quantitative real time polymerase chain reaction). Earlier studies have shown that this technology possesses essential advantages in comparison to IHC [8-10].

The present study contains an analytical validation of MammaTyper® with respect to various parameters (laboratory site, content of tumor cells in the sample, method of RNA preparation). Therefore FFPE breast cancer samples, covering the whole range of the clinically expected levels of expression of the target genes, were measured under various conditions at three different sites and using different RT-qPCR systems with MammaTyper®.

At a single site, the agreement between the results for the two tested RT-qPCR systems were 100 % for ERBB2, 96.9 % for ESR1, 97.2 % for PGR and 98.6 % for MKI67. MammaTyper® achieved in total a mean correlation between the markers and the sites of more than 96 %. The individual determination of the markers with MammaTyper® was stable up to a 64-fold dilution of a typical clinical sample. The MammaTyper® results were also unaffected by up to 80% of surrounding non-tumor tissue, including in situ carcinoma.

Dr. Sierk Poetting commented: “This means that the results with the MammaTyper® test kit are stable, even between different sites and under varying conditions. Thus, MammaTyper® allows standardized, precise and reproducible breast cancer subtyping.”

With this accurate, quantitative and reproducible determination of biomarkers, MammaTyper® can help to improve breast cancer diagnosis.

References

1 Laible M et al. (2016) Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer. DOI: 10.1186/s12885-016-2476-x (Published online 07 July 2016).

2 Wirtz Ralph M et al. (2016) Biological subtyping of early breast cancer: a study comparing RT-qPCR with immunohistochemistry. Breast Cancer Res Treat. DOI 10.007/s10549-016-3835-7 (Published online 24 May 2016)

3 Hammond MEH, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al., American Society of Clinical Oncology, College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med. 2010 Jul;134(7):e48–72.

4 Wolff AC, Hammond MEH, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al., American Society of Clinical Oncology, College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007 Jan 1;25(1):118–45.

5 De Dueñas EM, Hernández AL, Zotano AG, Carrión RMP, López-Muñiz JIC, Novoa SA, et al. Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study. Breast Cancer Res Treat. 2014 Feb;143(3):507–15.

6 Orlando L, Viale G, Schiavone P, Fedele P, Nacci A, Rizzo P, et al. Discordance in pathology report after central pathology review in early breast cancer and its impact on treatment choice. ASCO Meeting Abstracts. 2011 May 20;29(15_suppl):585.

7 Polley M-YC, Leung SCY, McShane LM, Gao D, Hugh JC, Mastropasqua MG, et al., International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group. An international Ki67 reproducibility study. J Natl Cancer Inst. 2013 Dec 18;105(24):1897–906.

8 Lehmann-Che J, Amira-Bouhidel F, Turpin E, Antoine M, Soliman H, Legres L, et al. Immunohistochemical and molecular analyses of HER2 status in breast cancers are highly concordant and complementary approaches. Br J Cancer. 2011 May 24;104(11): 1739–46.

9 Susini T, Bussani C, Marini G, Nori J, Olivieri S, Molino C, et al. Preoperative assessment of HER-2/neu status in breast carcinoma: The role of quantitative real-time PCR on core-biopsy specimens. Gynecologic Oncology. 2010 Feb 1;116(2):234–9.

10 Wilson TR, Xiao Y, Spoerke JM, Fridlyand J, Koeppen H, Fuentes E, et al. Development of a robust RNA-based classifier to accurately determine ER, PR, and HER2 status in breast cancer clinical samples. Breast Cancer Res Treat. 2014 Nov;148(2):315–25.