Prediction of response to neoadjuvant chemotherapy by MammaTyper® across breast cancer subtypes: A retrospective cross-sectional study
Francesco Schettini,
Silvana Saracchini,
Anna Bassini,
Wally Marus,
Serena Corsetti,
Ilaria Specogna,
Manuela Bertola,
Elvia Micheli,
Ralph M. Wirtz,
Mark Laible,
Uğur Şahin,
Carla Strina,
Manuela Milani,
Sergio Aguggini,
Richard Tancredi,
Elena Fiorio,
Sandro Sulfaro,
Daniele Generali
Affiliations
Francesco Schettini
Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain; Corresponding author. Hospital Clinic of Barcelona, Translational Genomics and Targeted Therapies in Solid Tumors Group, IDIBAPS, C. Casanova 143, 08036, Barcelona, Spain.
Silvana Saracchini
IRCCS CRO di Aviano, Aviano, Italy
Anna Bassini
Azienda per l’Assistenza Sanitaria 5 Friuli Occidentale, “Santa Maria degli Angeli” Hospital, Pordenone, Italy
Wally Marus
Azienda per l’Assistenza Sanitaria 5 Friuli Occidentale, “Santa Maria degli Angeli” Hospital, Pordenone, Italy
Serena Corsetti
IRCCS CRO di Aviano, Aviano, Italy
Ilaria Specogna
Azienda per l’Assistenza Sanitaria 5 Friuli Occidentale, “Santa Maria degli Angeli” Hospital, Pordenone, Italy
Manuela Bertola
IRCCS CRO di Aviano, Aviano, Italy
Elvia Micheli
Azienda per l’Assistenza Sanitaria 5 Friuli Occidentale, “Santa Maria degli Angeli” Hospital, Pordenone, Italy
Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy
Manuela Milani
Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy
Sergio Aguggini
Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy
Richard Tancredi
Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy
Elena Fiorio
Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, 37134 Verona, Italy
Sandro Sulfaro
Azienda per l’Assistenza Sanitaria 5 Friuli Occidentale, “Santa Maria degli Angeli” Hospital, Pordenone, Italy
Daniele Generali
Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; Corresponding author. Department of Medicine, Surgery and Health Sciences University of Trieste Strada di Fiume 447, 34149, Trieste, Italy.
Background: Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or progesterone receptor (PR) positive/HER2-negative BC is questioned because of the low pathologic complete response (pCR) rates. This retrospective study assessed the mRNA-based MammaTyper® assay's capability of predicting pCR with NACT, and ER, PR, Ki67, and HER2 status at immunohistochemical (IHC) through transcriptomics. Methods: Diagnostic biopsies from 76 BC patients treated at the Cremona Hospital between 2012-2018 were analyzed. Relative mRNA expression levels of ERBB2, ESR1, PGR, and MKI67 were measured using the MammaTyper® kit and integrated into a pCR score. Predicting capability of pCR and standard IHC biomarkers could be assessed with ROC curves in 75 and 76 patients, respectively. Results: Overall, 68.0% patients obtained a MammaTyper® high-score and 32.0% a MammaTyper® low-score. Among high-score patients, 62.7% achieved pCR, compared to 16.7% in the low-score group (p = 0.0003). The binary MammaTyper® score showed good prediction of pCR in the overall cohort (area under curve [AUC] = 0.756) and in HR+/HER2-negative cases (AUC = 0.774). In cases with residual disease, the continuous MammaTyper® score correlated moderately with residual tumor size and decrease in tumor size. MammaTyper® showed substantial agreement with IHC for ESR1/ER and ERBB2/HER2, and moderate agreement for PGR/PR and MKI67/Ki67. Conclusion: Overall, MammaTyper® pCR score may serve as a standardized tool for predicting NACT response in HR+/HER2-negative BC, potentially guiding treatment strategies. Additionally, it could provide a more standardized and reproducible assessment of ER, PR, HER2, and Ki67 status.
