- First comparison of a biomarker analysis by RT-qPCR (MammaTyper®) versus visual or computer-assisted immunohistochemistry (IHC) in subtyping mammary carcinomas
- Significantly more precise prediction of pathologically complete remission in a neoadjuvant setting with MammaTyper® compared to manual or computer-assisted IHC; better therapy stratification and possible avoidance of unnecessary therapies
- MammaTyper® provides reliable quantitative determination of MKI67-mRNA expression
Mainz, February 15, 2017: BioNTech Diagnostics GmbH, a subsidiary of BioNTech AG, announces the publication of further study data which again document the superiority of the in-vitro diagnostic MammaTyper® test (CE marked IVD) over immunohistochemical detection methods (IHC) . “The special feature of the currently published performance evaluation study is the fact that, for the first time, results of gene expression analysis with MammaTyper® were not only compared with results of manual microscopic analysis of immunohistochemical specimens but also with computer-assisted image analysis“, emphasized Dr. Sierk Pötting, Managing Director of BioNTech Diagnostics GmbH. The study used formalin-fixed, paraffin-embedded (FFPE) routine biopsy samples from breast cancer patients who had participated in a randomized neoadjuvant study . These samples were analyzed with the three methods prospectively and retrospectively. In the currently published study, as well as in previous publications [3,4], MammaTyper® demonstrated a significant superiority in the quantitative determination of the proliferation marker MKI67 (Ki-67) compared to IHC. Therefore MammaTyper® achieves significantly higher specificity than IHC in the identification of a possible pathological complete remission after neoadjuvant therapy. Prof. Dr. Hans-Peter Sinn, University of Heidelberg and head of the study summarized the results as follows: “The study demonstrates that MammaTyper® is able to reliably prognosticate tumor proliferation activity and the response to neoadjuvant therapy. That means patients may be spared unnecessary treatments“.
The classification of tumors in luminal, basal and HER2-amplified subtypes by the immunohistochemical markers estrogen receptor (ER), progesterone receptor (PR), HER2 and the proliferation marker Ki-67 provides the basis of biological subtyping and (neo)adjuvant therapy decisions for mammary carcinomas . Moreover, since the 2013 St Gallen Conference, the proliferation marker Ki-67 has also been confirmed for the definition of the intrinsic subtypes Luminal A and Luminal B-like . An earlier study in a neoadjuvant setting was able to show that high Ki-67 values are consistently associated with higher rates of pathological complete remission . The current standard method for detection of the Ki-67 proliferation marker as well as the biomarkers ER and PR is manual microscopic immunohistochemistry which has, however, been debated for some time due to the great intra- and inter-observer variability [7,8].
Results of the determination of biomarkers ESR1 (ER) and PGR (PR) in the currently published study again confirm the good correlation of MammaTyper® with immunohistochemistry results, showing a slightly higher correlation of MammaTyper® and computer-assisted immunohistochemistry (ER/ESR1: 91.23 %, p<0.0001; PR/PGR: 92.9 %, p < 0.0001). In contrast, MammaTyper® and computer-assisted IHC image analysis achieved , as expected, moderate correlation (Spearman’s r = 0.5; p = 0.0001) in the detection of the proliferation marker MKI67 (Ki-67). However, correlated with clinical progress data, MammaTyper® proved to be significantly superior to IHC – especially in predicting the response to neoadjuvant therapy derived from MKI67 determination.
The current study shows again that MammaTyper® is an interesting and reliable alternative to the currently customary IHC detection methods. Moreover, MammaTyper® offers the possibility for an improved prediction of pathological complete remission after neoadjuvant chemotherapy.
Therefore, MammaTyper could contribute to a well-founded therapy decision which could spare breast cancer patients unecessary treatments in the future.
- Sinn H-P et al. (2017) Comparison of immunohistochemistry with PCR for assessment of ER, PR, and Ki-67 and prediction of pathological complete response in breast cancer. BMC Cancer 17:124.
- Schneeweiss, Marme, Ruiz, et al. (2011). “A randomized phase II trial of doxorubicin plus pemetrexed followed by docetaxel versus doxorubicin plus cyclophosphamide followed by docetaxel as neoadjuvant treatment of early breast cancer.” Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 22(3): 609-617.
- 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).
- 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 201616:398, DOI: 10.1186/s12885-016-2476-x, published online 7 July 2016.
- Goldhirsch, Winer, Coates, et al. (2013). “Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013.” Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 24(9): 2206-2223.
- Coates AS et al. (2015) Tailoring therapies – improving the management of early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 24(9): 2206-2223.
- Polley, Leung, Gao, et al. (2015). “An international study to increase concordance in Ki67 scoring.” Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc.
- Polley, Leung, McShane, et al. (2013). “An international Ki67 reproducibility study.” Journal of the National
Cancer Institute 105(24): 1897-1906.
- Di Cataldo, Ficarra and Macii (2012). “Computer-aided techniques for chromogenic immunohistochemistry: status and directions.” Computers in biology and medicine 42(10): 1012-1025.
- Noske, Loibl, Darb-Esfahani, et al. (2011). “Comparison of different approaches for assessment of HER2 expression on protein and mRNA level: prediction of chemotherapy response in the neoadjuvant GeparTrio trial (NCT00544765).” Breast cancer research and treatment 126(1): 109-117.
- Yerushalmi, Woods, Ravdin, et al. (2010). “Ki67 in breast cancer: prognostic and predictive potential.” TheLancet. Oncology 11(2): 174-183.