Abstract Background: Accurate HER2 status assessment is crucial for guiding treatment decisions in breast cancer. MammaTyper® is a CE-marked in-vitro diagnostic device utilizing real-time quantitative PCR (qRT-PCR) to quantify mRNA transcripts of ERBB2, ESR1, PGR, and MKI67. It provides an objective and standardized classification of breast cancer into intrinsic subtypes (Luminal A, Luminal B, HER2-enriched, and Triple-Negative), offering prognostic and predictive information that complements traditional immunohistochemistry (IHC). MammaTyper®'s high reproducibility and sensitivity are particularly valuable when subjective interpretation of IHC presents challenges. Objective: This study aimed to analyses whether the MammaTyper® platform improves the classification of HER2-equivocal breast cancer cases and to assess its concordance with FISH-based methods. Methods: We analysed 93 breast cancer patients. Estrogen receptor (ER) and progesterone receptor (PR) status, along with Ki67 index, were determined by IHC. HER2 status was initially assessed by IHC and FISH. MammaTyper® was then performed to classify intrinsic subtypes and determine HER2 status based on ERBB2 mRNA levels. Concordance between MammaTyper®, IHC, and FISH was evaluated. Results: Of the 93 patients, 83 (89%) were ER-positive, 42 (45%) PR-positive, and 51 (55%) had a high Ki67 index by IHC. Forty-two cases (45%) were classified as HER2-positive by IHC and FISH. MammaTyper® confirmed HER2-positivity in 25 (60%) of these cases. Among the 51 HER2-negative cases by IHC and FISH, MammaTyper® was positive in only 8 (15%). The overall concordance between MammaTyper® and the IHC/FISH combined assessment was 73%. Specifically, concordance was 60% for IHC/FISH-positive cases and 84% for IHC/FISH-negative cases. Of the 32 cases classified as HER2-positive by MammaTyper®, 23 (71%) had a HER2 FISH ratio of ≥2. Conversely, among the 55 cases classified as HER2-negative by MammaTyper®, 17 (31%) had a HER2 FISH ratio of ≥2. MammaTyper® showed a 72% concordance with IHC for HER2 phenotype determination, identifying a lower proportion of HER2-positive tumors (34%) compared to IHC (45%). This concordance was notably higher (84%) in HER2-negative cases. Conclusion: MammaTyper® demonstrates substantial concordance with IHC and FISH for HER2 status determination, particularly in HER2-negative cases. It identifies a smaller subset of HER2-positive tumors compared to IHC, suggesting its potential to refine the selection of patients for HER2-targeted therapies. Further clinical utility should be assessed by correlating MammaTyper® results with treatment response and survival outcomes. Citation Format: A. VELASCO, I. URDANIBIA, G. RODRIGUEZ, N. TUSET, G. ARIADNA, S. MORALES. Improving HER2 Status Assessment in Breast Cancer with MammaTyper®: Focus on Equivocal Cases abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-04-02.
Velasco et al. (Tue,) studied this question.