Abstract P1-10-23: Prediction of pathological complete response (pCR) upon neoadjuvant chemotherapy by MammaTyper® pCR score
Authors: Saracchini Silvana , Bassini Anna , Marus Wally , Corsetti Serena , Specogna Ilaria , Bertola Manuela , Micheli Elvia , Wirtz Ralph M , Laible Mark , Sahin Ugur , Generali Daniele , Sulfaro Sandro 
Published: March 2020

Abstract
Background: Neoadjuvant chemotherapy (NACT) (+/- anti HER2) is the preferred therapy for triple negative and HER2 positive subtype breast tumors. In Luminal subtype breast tumors, NACT is used to downstage large inoperable tumors and enable breast conserving therapy. However, this subgroup of patients may be overtreated as many Luminal subtype tumors do not respond to NACT due to the low rate of proliferating tumor cells. Herein, we tested the MammaTyper® pCR score as a predictor of therapy success measured as pCR in a retrospective analysis of archived samples from a single center. Methods: 85 FFPE biopsy samples from the years 2012-2018 were sourced from the archive. Samples with &gt;20% tumor cell content were subjected to RNA extraction. Relative mRNA expression levels of ERBB2, ESR1, PGR and MKI67 were determined by RT-qPCR using the CE-IVD MammaTyper® kit. The continuous expression values were integrated into a prediction score (pCR-score) using a pre-defined algorithm and cutoff. The association of continuous and binary pCR-score results with pCR (defined as ypT0/Tis) and partial response was analyzed. Results: Marker positivity rates of the 75 samples included in the final analysis were 62.7% for ER, 53.3% for PR, 40.0% for HER2 and 94.7% for Ki67 (≥20% positive cells). 42.7% of patients were pre-menopausal and all samples except one were grade 3. pCR rates over all samples and in hormone receptor (HR) positive/HER2 negative patients only were 48.0% and 20.0%, respectively. Binary pCR-score result was significantly associated with pCR over all patients (Sensitivity: 88.9%, Specificity: 51.3%, PPV: 62.8%, NPV: 83.3%) and also in HR positive/HER2 negative patients only (Sensitivity: 83.3%, Specificity: 70.8%, PPV: 41.7%, NPV: 94.4%). ROC analysis revealed a good association of the continuous pCR-score with achievement pCR over all patients (AUC=0.756) and in the subgroup of HR+/HER2- patients (AUC=0.774). pCR rates according to St Gallen surrogate subtype definition were similar for IHC and RT-qPCR defined subtypes in Triple Negative (80.0% and 78.6% respectively) and in the HER2+ non luminal subtype (75.0%, and 70.0% respectively). In tumors with incomplete response the continuous pCR-score was significantly associated with residual tumor size (Spearman rs: -0.477 p-value: 0.0021) and %-decrease of tumor size (Spearman rs: 0.388, p-value: 0.0147). Conclusion: The MammaTyper® pCR score may serve as a standardized tool to predict response to NACT based on a pre-treatment biopsy. For patients with inoperable Luminal tumors and low predicted probability of pCR, neo-adjuvant aromatase inhibitor alone or combined with the new generation of TKIs such as CDK4/6 inhibitors or Pi3KCa/mTOR inhibitors may be an alternative for downstaging of tumors.
Citation Format: Silvana Saracchini, Anna Bassini, Wally Marus, Serena Corsetti, Ilaria Specogna, Manuela Bertola, Elvia Micheli, Ralph M Wirtz, Mark Laible, Ugur Sahin, Daniele Generali, Sandro Sulfaro. Prediction of pathological complete response (pCR) upon neoadjuvant chemotherapy by MammaTyper® pCR score [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-23.