Recommendations for streamlining precision medicine in breast cancer care in Latin America.

BACKGROUND: The incidence of breast cancer (BC) in LMICs has increased by more than 20% within the last decade. In areas such as Latin America (LA), addressing BC at national levels evoke discussions surrounding fragmented care, limited resources, and regulatory barriers. Precision Medicine (PM), specifically companion diagnostics (CDx), links disease diagnosis and treatment for better patient outcomes. Thus, its application may aid in overcoming these barriers. RECENT FINDINGS: A panel of LA experts in fields related to BC and PM were provided with a series of relevant questions to address prior to a multi-day conference. Within this conference, each narrative was edited by the entire group, through numerous rounds of discussion until a consensus was achieved. The panel proposes specific, realistic recommendations for implementing CDx in BC in LA and other LMIC regions. In these recommendations, the authors strived to address all barriers to the widespread use and access mentioned previously within this manuscript. CONCLUSION: This manuscript provides a review of the current state of CDx for BC in LA. Of most importance, the panel proposes practical and actionable recommendations for the implementation of CDx throughout the Region in order to identify the right patient at the right time for the right treatment.

Precision cytopathology: expanding opportunities for biomarker testing in cytopathology.

Precision cytopathology refers to therapeutically linked biomarker testing in cytopatology, a dynamically growing area of the discipline. This review describes basic steps to expand precision cytopathology services. Focusing exclusively on solid tumors, the review is divided into four sections: Section 1: Overview of precision pathology- opportunities and challenges; Section 2: Basic steps in establishing or expanding a precision cytopathology laboratory; Section 3: Cytopathology specimens suitable for next generation sequencing platforms; and Section 4: Summary. precision cytopathology continues to rapidly evolve in parallel with expanding targeted therapy options. Biomarker assays (companion diagnostics) comprise a multitude of test types including immunohistochemistry, in situ hybridization and molecular genetic tests such as PCR and next generation sequencing all of which are performable on cytology specimens. Best practices for precision cytopathology will incorporate traditional diagnostic approaches allied with careful specimen triage to enable successful biomarker analysis. Beyond triaging, cytopathologists knowledgeable about molecular test options and capabilities have the opportunity to refine diagnoses, prognoses and predictive information thereby assuming a lead role in precision oncology biomarker testing.

Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population.

Cervical cancer is a major health concern among women in Latin America due to its high incidence and mortality. Therefore, the discovery of molecular markers for cervical cancer screening and triage is imperative. The aim of this study was to use a genome wide DNA methylation approach to identify novel methylation biomarkers in cervical cancer. DNA from normal cervical mucosa and cervical cancer tissue samples from Chile was enriched with Methylated DNA Immunoprecipitation (MeDIP), hybridized to oligonucleotide methylation microarrays and analyzed with a stringent bioinformatics pipeline to identify differentially methylated regions (DMRs) as candidate biomarkers. Quantitative Methylation Specific PCR (qMSP) was used to study promoter methylation of candidate DMRs in clinical samples from two independent cohorts. HPV detection and genotyping were performed by Reverse Line Blot analysis. Bioinformatics analysis revealed GGTLA4, FKBP6, ZNF516, SAP130, and INTS1 to be differentially methylated in cancer and normal tissues in the Discovery cohort. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). ZNF516 promoter methylation was the best biomarker, with both sensitivity and specificity of 90% (AUC = 0.92), results subsequently corroborated in a Prevalence cohort. Together, ZNF516 and FKBP6 exhibited a sensitivity of 84% and specificity of 81%, when considering both cohorts. Our genome wide DNA methylation assessment approach (MeDIP-chip) successfully identified novel biomarkers that differentiate between cervical cancer and normal samples, after adjusting for age and HPV status. These biomarkers need to be further explored in case-control and prospective cohorts to validate them as cervical cancer biomarkers.