Validation of the MammaTyper® pathological complete response (pCR)-score as a predictor for response after neoadjuvant chemotherapy (NACT) in patients with early breast cancer (BC) (2018)

Background: Prediction of the response to NACT in early BC patients (pts) can lead to improved treatment decisions. The MammaTyper® test can be used to predict the probability of pCR after NACT by integrating accurate and reproducible assessment of ERBB2, ESR1, PGR and MKI67 mRNA into a standardized prediction model (Varga et al. Breast Cancer Research 2017). Methods: Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor samples of pts with cT1-2 BC enrolled in in the single arm phase II TECHNO trial (Untch et al. JCO 2011) and the randomised phase III PREPARE trial (Untch et al. Ann Oncol. 2011). MammaTyper®, a molecular in vitro diagnostic RT-qPCR test, was used to assess the expression of ERBB2 (HER2), ESR1 (ER), PGR (PR) and MKI67 (Ki67) genes from which a predefined continuous score was calculated. The study aimed to validate the MammaTyper® pCR-score for predicting pCR (ypT0 ypN0) after NACT in BC. Pts were classifed into a low or high score group according to a predefined cutoff: score ≤41 predicts a low probability of pCR; score ≥42 predicts a high pCR rate. Results: A total of 324 pts with available FFPE samples and MammaTyper® measurements were analyzed. The MammaTyper® score was significantly associated with an increased pCR rate (AUC=0.805, p < 0.001). Similarly, pts with high MammaTyper® score (N = 159) had more frequently pCR compared to pts with low score (N = 165) (30.2% vs 3.0%, respectively; OR = 13.84 [95%CI 5.34-35.86], p < 0.001). In addition, the MammaTyper® pCR-score remained significantly predicitve when adjusted for age, nodal status, tumor grade and treatment (OR = 10.90 [95%CI 3.38-35.16], p < 0.001). Within the non-pCR subgroup, pts with low score had a significantly longer disease-free (DFS) and overall (OS) survival compared to pts with high score (DFS HR = 1.59, 95%-CI 1.04-2.44, p = 0.032; OS HR = 2.85, 95%-CI 1.62-5.00, p < 0.001). Conclusions: The MammaTyper® pCR-score predicts pCR after NACT and seems to improve prognosis additionally to clinical predictors in pts with early BC. Its utility with regard to conventional ER, PR, Ki67 and HER2 has to be analyzed in future studies. Legal entity responsible for the study: GBG Forschungs GmbH and BioNTech Diagnostics GmbH, Mainz. Funding: BioNTech Diagnostics GmbH, Mainz, Germany. Disclosure: P.A. Fasching: Personal fees: Celgene, during the conduct of the study; Grants and personal fees: Novartis; Personal fees: Pfizer, Roche, Teva, outside the submitted work. M. Laible: Personal fees: BioNTech Diagnostics GmbH, outside the submitted work; Employee: BioNTech Diagnostics GmbH); Patent WO 2015/024942 pending, new patent application pending. K.E. Weber: Grants and non-financial support: BioNTech Diagnostics GmbH, Mainz, Germany, during the conduct of the study; Patent EndoPredict issued. C. Denkert: Personal fees: Teva, Novartis, Pfizer, Roche, Amgen, MSD Oncology; Other: Sividon Diagnostics, outside the submitted work. K. Schlombs: Personal fees: BioNTech Diagnostics GmbH, outside the submitted work; Patent WO 2015/024942 pending; New patent application pending. F. Marme: Personal fees; Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, GenomicHealth, CureVac, Eisai, outside the submitted work. S. Loibl: Grants: AbbVie, Amgen, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Teva, Vifor during the conduct of the study and outside the submitted work. All other authors have declared no conflicts of interest.