Supplementary_data_table_S1.xlsx

<b>Introduction:</b> Breast cancer (BC) is the most common cancer in women worldwide, with an increasing incidence in Mexico, especially among women under 50 years old. Early diagnosis and personalized treatment are crucial for improving the patient outcomes of Mexican women. <b>Methods and Findings:</b> Standardized procedures for sample collection, cell-free DNA (cfDNA) extraction, and next-generation sequencing (NGS) analysis were developed and applied in Mexico and the UK. Plasma samples were collected and processed to extract cfDNA, and a targeted NGS panel was used to analyze 152 commonly mutated regions in 12 clinically relevant genes (<i>AKT1, EGFR, ERBB2, ERBB3, ESR1, FBXW7, KRAS, PIK3CA, SF3B1, TP53, FGFR1, CCND1</i>). The study analyzed plasma samples from 104 Mexican and 63 British patients with BC. Variants were identified in 45% of the Mexican samples, which were identified in five genes. The <i>TP53</i> gene had the highest number of variants (n=54), followed by <i>PIK3CA</i> (n=13), <i>ERBB2 </i>(n=2)<i>, </i>with <i>CCND1</i>, and <i>FBXW7</i> having one variant each. SNVs and INDELs were the two most predominant variant types. Amplifications of <i>CCND1</i> and <i>ERBB2</i> were detected in two patients each, both with targeted therapies for Palbociclib and Trastuzumab, respectively. Furthermore, 90% of advanced disease (stage IV) patients had detectable variants indicating circulating tumour DNA (ctDNA). Of note nine patients from the UK (15%) had <i>ESR1</i> mutations detected suggesting resistance to endocrine therapy. <b>C</b><b>onclusions:</b> Liquid biopsy analysis using cfDNA is a promising tool for identifying clinically relevant genetic variants in Mexican BC patients. This method provides a non-invasive alternative for disease monitoring and therapy guidance, highlighting the potential for personalized cancer care in Mexico. Further studies are needed to confirm these findings and explore ctDNA analysis integration into routine clinical practice.