Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer

• Published in: International journal of molecular sciences 2022-12, Vol.23 (24), p.15515
• Main Authors: Crocamo, Susanne, Binato, Renata, Dos Santos, Everton Cruz, de Paula, Bruno, Abdelhay, Eliana
• Format: Article
• Language: English
• Subjects: Angiogenesis; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Apoptosis; Biomarkers; Biopsy; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer therapies; Cell growth; Chemotherapy; Cyclophosphamide; Cyclophosphamide - therapeutic use; Cytochrome; differential expression genes; DNA microarrays; Doxorubicin; ErbB-2 protein; Estrogens; Female; Gene expression; Genes; Growth factors; HER2-positive; Humans; Kinases; Metabolism; Metabolites; Metastasis; Mevalonate pathway; Monoclonal antibodies; Neoadjuvant Therapy; Patients; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Signal transduction; Subgroups; Therapeutic targets; Trastuzumab; Trastuzumab - therapeutic use; Treatment Outcome; Tumors; Zoledronic acid; Zoledronic Acid - therapeutic use
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232415515

Breast cancer is a heterogeneous disease with distinct clinical and molecular characteristics. Scientific advances in molecular subtype differentiation support the understanding of cellular signaling, crosstalk, proliferation, survival, migration, and invasion mechanisms, allowing the development of new molecular drug targets. The breast cancer subtype with super expression and/or amplification of human growth factor receptor 2 (HER2) is clinically aggressive, but prognosis significantly shifted with the advent of anti-HER2 targeted therapy. Zoledronic-acid (ZOL) combined with a neoadjuvant Trastuzumab-containing chemotherapy regimen (Doxorubicin, Cyclophosphamide followed by Docetaxel, Trastuzumab) increased the pCR rate in a RH-positive/ HER2-positive subgroup, according to the phase II Zo-NAnTax trial. To verify genes that could be related to this response, a microarray assay was performed finding 164 differentially expressed genes. Silico analysis of these genes showed signaling pathways related to growth factors, apoptosis, invasion, and metabolism, as well as differentially expressed genes related to estrogen response. In addition, the RAC3 gene was found to interact with the MVD gene, a member of the mevalonate pathway. Taken together, these results indicate that RH-positive/ HER2-positive patients present gene alterations before treatment, and these could be related to the improvement of pCR.