Prediction of response to neoadjuvant chemotherapy by MammaTyper® across breast cancer subtypes: A retrospective cross-sectional study

Breast. 2024 Aug:76:103753. doi: 10.1016/j.breast.2024.103753. Epub 2024 May 25.

Abstract

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.

Keywords: Breast cancer; Hormone receptor; MammaTyper; Neoadjuvant; Subtypes; pCR.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Chemotherapy, Adjuvant
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neoadjuvant Therapy*
  • Predictive Value of Tests
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • ROC Curve
  • Receptor, ErbB-2* / analysis
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen* / analysis
  • Receptors, Estrogen* / metabolism
  • Receptors, Progesterone* / analysis
  • Receptors, Progesterone* / metabolism
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Receptor, ErbB-2
  • Receptors, Progesterone
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Ki-67 Antigen
  • RNA, Messenger
  • MKI67 protein, human