Assessment of ERBB2 and HER2 expression in metastatic breast cancer using the nCounter® system and a 100-gene scale

• Published in: Opukholi zhenskoĭ reproduktivnoĭ sistemy Vol. 19; no. 3; pp. 30 - 36
• Main Authors: Paltuev, R. M. , Volynshchikova, O. A. , Abdullaeva, Sh. R. , Aleksakhina, S. N. , Artemyeva, A. S. , Baychorov, E. A. , Bakharev, S. Yu. , Belaya, Yu. A. , Bozhok, A. A. , Vasin, V. A. , Vladimirov, V. I. , Vorontsov, A. Yu. , Gaysina, E. A. , Gofman, A. A. , Dmitriev, V. N. , Imyanitov, E. N. , Klimenko, V. V. , Komyakhov, A. V. , Konstantinova, M. M. , Kopp , M. V. , Kudaybergenova, A. G. , Lalak, I. A. , Matevosyan, D. L. , Mudzhiri, N. M. , Poltareva, O. V. , Sevryukova, O. I. , Semiglazov, V. F. , Semiglazova, T. Yu. , Urezkova, M. M. , Chichkanova, A. S. , Churilova, L. A. , Shomova, M. V.
• Format: Journal Article
• Language: English; Russian
• Published: ABV-press 27.10.2023
• Subjects: gene expression; her2; metastatic breast cancer; molecular diagnostics; multigene panel; multigene signature; ncounter
• ISSN: 1994-4098; 1999-8627
• DOI: 10.17650/1994-4098-2023-19-3-30-36

Background . Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy. Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor. Materials and methods . We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color-coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer. Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+/ISH±); and 15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15 000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression. Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2-enriched molecular class and the response to anti-HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.