Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Determining the Factors Predicting the Response to Anti-HER2 Therapy in HER2-Positive Breast Cancer Patients

Version 1 : Received: 23 December 2021 / Approved: 28 December 2021 / Online: 28 December 2021 (09:58:26 CET)

How to cite: You, J.Y.; Park, K.H.; Lee, E.; Kwon, Y.; Kim, K.; Nam, S.; Kim, D.; Bae, J.W. Determining the Factors Predicting the Response to Anti-HER2 Therapy in HER2-Positive Breast Cancer Patients. Preprints 2021, 2021120441 (doi: 10.20944/preprints202112.0441.v1). You, J.Y.; Park, K.H.; Lee, E.; Kwon, Y.; Kim, K.; Nam, S.; Kim, D.; Bae, J.W. Determining the Factors Predicting the Response to Anti-HER2 Therapy in HER2-Positive Breast Cancer Patients. Preprints 2021, 2021120441 (doi: 10.20944/preprints202112.0441.v1).

Abstract

Background: We aimed to identify overexpressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant therapy with trastuzumab in HER2-positive breast cancer patients. Methods: We recruited 64 women with breast cancer and categorized them into three groups according to anti-HER2 therapy response. RNA from twenty core needle biopsy paraffin-embedded tissues and four cultured cell was extracted, reverse transcribed, and subjected to microarray. The obtained data were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and database for annotation, visualization, and integrated discovery. Results: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines (3,224 upregulated and 3,432 downregulated). Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in complete response group. Conclusions: This multigene assay-based study provides insights into breast cancer signal transduction and the possible prediction of treatment response to targeted therapies such as trastuzumab.

Keywords

HER2; neoadjuvant; pathologic complete response; trastuzumab

Subject

MEDICINE & PHARMACOLOGY, Oncology & Oncogenics

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